ABCD Study publications are authored by ABCD investigators, collaborators, and non-ABCD researchers.

The analysis methodologies, findings, and interpretations expressed in these publications are those of the authors and do not constitute an endorsement by the ABCD Study®.

2023
Understanding Social Determinants of Brain Health During Development

Barch DM, Luby JL. Understanding Social Determinants of Brain Health During Development. Am J Psychiatry, Editorial. 2023 Feb 1, https://doi.org/10.1176/appi.ajp.20220991

Racial Disparities in Adversity During Childhood and the False Appearance of Race-Related Differences in Brain Structure

Dumornay NM, Lebois LAM, Ressler KJ, Harnett NG. Racial Disparities in Adversity During Childhood and the False Appearance of Race-Related Differences in Brain Structure. Am J Psychiatry. 2023 Feb 1;180(2):127-138. doi: 10.1176/appi.ajp.21090961. PMID: 36722118.

Objective: Black Americans in the United States are disproportionately exposed to childhood adversity compared with White Americans. Such disparities may contribute to race-related differences in brain structures involved in regulating the emotional response to stress, such as the amygdala, hippocampus, and prefrontal cortex (PFC). The authors investigated neuroanatomical consequences of racial disparities in adversity.

Methods: The sample included 7,350 White American and 1,786 Black American children (ages 9-10) from the Adolescent Brain Cognitive Development Study (public data release 2.0). Structural MRI data, parent and child self-reports of adversity-related measures, and U.S. Census neighborhood data were used to investigate the relationship between racial disparities in adversity exposure and race-related differences in brain structure.

Results: Black children experienced more traumatic events, family conflict, and material hardship on average compared with White children, and their parents or caregivers had lower educational attainment, lower income, and more unemployment compared with those of White children. Black children showed lower amygdala, hippocampus, and PFC gray matter volumes compared with White children. The volumes of the PFC and amygdala, but not the hippocampus, also varied with metrics of childhood adversity, with income being the most common predictor of brain volume differences. Accounting for differences in childhood adversity attenuated the magnitude of some race-related differences in gray matter volume.

Conclusions: The results suggest that disparities in childhood adversity contribute to race-related differences in gray matter volume in key brain regions associated with threat-related processes. Structural alterations of these regions are linked to cognitive-affective dysfunction observed in disorders such as posttraumatic stress disorder. More granular assessments of structural inequities across racial/ethnic identities are needed for a thorough understanding of their impact on the brain. Together, the present findings may provide insight into potential systemic contributors to disparate rates of psychiatric disease among Black and White individuals in the United States.

Polygenic Risk for Schizophrenia, Major Depression, and Post-traumatic Stress Disorder and Hippocampal Subregion Volumes in Middle Childhood

Pine JG, Paul SE, Johnson E, Bogdan R, Kandala S, Barch DM. Polygenic Risk for Schizophrenia, Major Depression, and Post-traumatic Stress Disorder and Hippocampal Subregion Volumes in Middle Childhood. Behav Genet. 2023 Jan 31. doi: 10.1007/s10519-023-10134-1. Epub ahead of print. PMID: 36720770.

Studies demonstrate that individuals with diagnoses for Major Depressive Disorder (MDD), Post-traumatic Stress Disorder (PTSD), and Schizophrenia (SCZ) may exhibit smaller hippocampal gray matter relative to otherwise healthy controls, although the effect sizes vary in each disorder. Existing work suggests that hippocampal abnormalities in each disorder may be attributable to genetic liability and/or environmental variables. The following study uses baseline data from the Adolescent Brain and Cognitive Development[Formula: see text] Study (ABCD Study[Formula: see text]) to address three open questions regarding the relationship between genetic risk for each disorder and hippocampal volume reductions: (a) whether polygenic risk scores (PGRS) for MDD, PTSD, and SCZ are related to hippocampal volume; (b) whether PGRS for MDD, PTSD, and SCZ are differentially related to specific hippocampal subregions along the longitudinal axis; and (c) whether the association between PGRS for MDD, PTSD, and SCZ and hippocampal volume is moderated by sex and/or environmental adversity. In short, we did not find associations between PGRS for MDD, PTSD, and SCZ to be significantly related to any hippocampal subregion volumes. Furthermore, neither sex nor enviornmental adversity significantly moderated these associations. Our study provides an important null finding on the relationship genetic risk for MDD, PTSD, and SCZ to measures of hippocampal volume.

Prenatal tobacco exposure associations with physical health and neurodevelopment in the ABCD cohort

Gonzalez MR, Uban KA, Tapert SF, Sowell ER. Prenatal tobacco exposure associations with physical health and neurodevelopment in the ABCD cohort. Health Psychol. 2023 Jan 30. doi: 10.1037/hea0001265. Epub ahead of print. PMID: 36716140.

Objective: To investigate the strength and reproducibility of the teratogenic impact of prenatal tobacco exposure (PTE) on child physical health and neurodevelopmental outcomes, in the context of intersecting sociodemographic and other prenatal correlates, and test if early postnatal health mediates PTE associations with childhood outcomes.

Method: Among 9-10-year-olds (N = 8,803) in the Adolescent Brain Cognitive Development Study, linear mixed-effect models tested PTE associations with birth and childhood outcomes of physical health, cognitive performance, and brain structure, controlling for confounding sociodemographic and prenatal health correlates. Mediation analysis tested the extent to which health at birth explained the associations between PTE and childhood outcomes.

Results: PTE was reported by 12% of mothers (8% [n = 738] pre-knowledge of pregnancy only, and 4% [n = 361] pre- and post-knowledge of pregnancy). PTE was highest for children with a risk for passive smoke exposure. Overall, children with any PTE had shorter breastfeeding durations than those without PTE, and PTE following knowledge of pregnancy was associated with being small for gestational age having lower birth weight, and obesity and lower cortical volume and surface area in childhood. Among children from high-parent education households, any PTE was related to lower cognitive performance, which was partially mediated by duration of breastfeeding.

Conclusions: PTE was linked to poorer health indicators at birth and neurodevelopmental outcomes at age 9-10 years in a large community cohort, independent of sociodemographic factors. Efficacious interventions for smoking-cessation during pregnancy are still needed and should incorporate support for breastfeeding to promote healthier development.

Executive Network Activation Moderates the Association between Neighborhood Threats and Externalizing Behavior in Youth

Conley, M.I., Rapuano, K.M., Benson-Williams, C. et al. Executive Network Activation Moderates the Association between Neighborhood Threats and Externalizing Behavior in Youth. Res Child Adolesc Psychopathol (2023). https://doi.org/10.1007/s10802-022-01003-2

Neighborhood threats can increase risk for externalizing problems, including aggressive, oppositional, and delinquent behavior. Yet, there is substantial variability in how youth respond to neighborhood threats. Difficulty with cognitive functioning, particularly in the face of emotional information, may increase risk for externalizing in youth who live in neighborhoods with higher threats. However, little research has examined: 1) associations between neighborhood threats and executive networks involved in cognitive functioning or 2) whether executive networks may amplify risk for externalizing in the context of neighborhood threats. Further, most research on neighborhood threats does not account for youth’s experiences in other social contexts. Utilizing the large, sociodemographically diverse cohort of youth (ages 9–10) included in the Adolescent Brain Cognitive DevelopmentSM Study, we identified four latent profiles of youth based on threats in their neighborhoods, families, and schools: low threat in all contexts, elevated family threat, elevated neighborhood threat, and elevated threat in all contexts. The elevated neighborhood threat and elevated all threat profiles showed lower behavioral performance on an emotional n-back task relative to low threat and elevated family threat profiles. Lower behavioral performance in the elevated neighborhood threat profile specifically was paralleled by lower executive network activity during a cognitive challenge. Moreover, among youth with lower executive network activity, higher probability of membership in the elevated neighborhood threat profile was associated with higher externalizing. Together, these results provide evidence that interactions between threats that are concentrated in youth’s neighborhoods and attenuated executive network function may contribute to risk for externalizing problems.

Sleep Quality and Duration in Children That Consume Caffeine: Impact of Dose and Genetic Variation in ADORA2A and CYP1A

Jessel CD, Narang A, Zuberi R, Bousman CA. Sleep Quality and Duration in Children That Consume Caffeine: Impact of Dose and Genetic Variation in ADORA2A and CYP1A. Genes. 2023; 14(2):289. https://doi.org/10.3390/genes14020289

Caffeine is the most consumed drug in the world, and it is commonly used by children. Despite being considered relatively safe, caffeine can have marked effects on sleep. Studies in adults suggest that genetic variants in the adenosine A2A receptor (ADORA2A, rs5751876) and cytochrome P450 1A (CYP1A, rs2472297, rs762551) loci are correlated with caffeine-associated sleep disturbances and caffeine intake (dose), but these associations have not been assessed in children. We examined the independent and interaction effects of daily caffeine dose and candidate variants in ADORA2A and CYP1A on the sleep quality and duration in 6112 children aged 9–10 years who used caffeine and were enrolled in the Adolescent Brain Cognitive Development (ABCD) study. We found that children with higher daily caffeine doses had lower odds of reporting > 9 h of sleep per night (OR = 0.81, 95% CI = 0.74–0.88, and p = 1.2 × 10−6). For every mg/kg/day of caffeine consumed, there was a 19% (95% CI = 12–26%) decrease in the odds of children reporting > 9 h of sleep. However, neither ADORA2A nor CYP1A genetic variants were associated with sleep quality, duration, or caffeine dose. Likewise, genotype by caffeine dose interactions were not detected. Our findings suggest that a daily caffeine dose has a clear negative correlation with sleep duration in children, but this association is not moderated by the ADORA2A or CYP1A genetic variation.

Gender Differences in Adolescents’ Affective Symptoms and Behavioral Disorders After Mild Traumatic Brain Injury

Veliz PT, Berryhill ME. Gender Differences in Adolescents’ Affective Symptoms and Behavioral Disorders After Mild Traumatic Brain Injury. J Head Trauma Rehabil. 2023 Jan 21. doi: 10.1097/HTR.0000000000000851. Epub ahead of print. PMID: 36689685.

Objective: Mild traumatic brain injuries (mTBI) are considered self-limiting and full recovery is expected. Recent studies identify deficits persisting years after mTBI. Large-scale prospective data permit testing the hypothesis that mTBI increases incidence of affective and behavioral symptoms after new, past, or new and past mTBI.

Setting: The study involved secondary analyses of survey responses from the Adolescent Brain Cognitive Development (ABCD) Study.

Participants: Adolescents in the ABCD Study (n = 11 869; Wave 1, aged 9-10 years; Wave 2, aged 11-12 years) whose parents reported a new (n = 157), past (n = 1318), or new and past (n = 50) mTBI on the Ohio State University Traumatic Brain Injury Identification Method short form were compared with controls who had no history of mTBI (n = 9,667).

Design: Multivariable binary logistic regression models examined associations between a new, past, or new and past mTBI and current affective (aggression, depression, anxiety) and behavioral (somatic, thought, social, attention, attention deficit hyperactivity disorder, conduct) disorders while controlling for demographic factors and baseline symptoms.

Main measures: The primary measure was parental reports of psychiatric and behavioral symptoms on the Child Behavior Checklist.

Results: Girls exhibited no significant effects after a new mTBI, although a past mTBI increased anxiety (adjusted odds ratios [aOR] = 1.83, 95% confidence interval [CI: 1.15-2.90]) and attention (1.89 [1.09-3.28]) problems. Girls with new and past mTBIs reported elevated anxiety (17.90 [4.67-68.7]), aggression (7.37 [1.49-36.3]), social (9.07 [2.47-33.30]), thought (7.58 [2.24-25.60]), and conduct (6.39 [1.25-32.50]) disorders. In boys, new mTBI increased aggression (aOR = 3.83, 95% CI [1.42-10.30]), whereas past mTBI heightened anxiety (1.91 [1.42-2.95]), but new and past mTBIs had no significant effects.

Conclusion: Adolescents are at greater risk of affective and behavioral symptoms after an mTBI. These effects differ as a function of gender and time of injury. Extended screening for mTBI history and monitoring of affective and behavioral disorders after mTBI in adolescents are warranted.

Characterizing Alcohol Expectancies in the ABCD Study: Associations with Sociodemographic Factors, the Immediate Social Environment, and Genetic Propensities

Johnson EC, Paul SE, Baranger DAA, Hatoum AS, Colbert SMC, Lin S, Wolff R, Gorelik AJ, Hansen I, Karcher NR, Bogdan R, Agrawal A. Characterizing Alcohol Expectancies in the ABCD Study: Associations with Sociodemographic Factors, the Immediate Social Environment, and Genetic Propensities. Behav Genet. 2023 Jan 20. doi: 10.1007/s10519-023-10133-2. Epub ahead of print. PMID: 36662388.

Alcohol expectancies (AEs) are associated with likelihood of alcohol initiation and subsequent alcohol use disorders. It is unclear whether genetic predisposition to alcohol use and/or related traits contributes to shaping how one expects to feel when drinking alcohol. We used the Adolescent Brain Cognitive Development study to examine associations between genetic propensities (i.e., polygenic risk for problematic alcohol use, depression, risk-taking), sociodemographic factors (i.e., parent income), and the immediate social environment (i.e., peer use and disapproval toward alcohol) and positive and negative AEs in alcohol-naïve children (max analytic N = 5,352). Mixed-effect regression models showed that age, parental education, importance of the child’s religious beliefs, adverse childhood experiences, and peer disapproval of alcohol use were associated with positive and/or negative AEs, to varying degrees. Overall, our results suggest several familial and psychosocial predictors of AEs but little evidence of contributions from polygenic liability to problematic alcohol use or related phenotypes.

Decoupling sleep and brain size in childhood: An investigation of genetic covariation in the Adolescent Brain Cognitive Development Study®

Hernandez LM, Kim M, Hernandez C, Thompson W, Fan CC, Galván A, Dapretto M, Bookheimer SY, Fuligni A, Gandal M. Decoupling sleep and brain size in childhood: An investigation of genetic covariation in the Adolescent Brain Cognitive Development Study®. Biological Psychiatry Global Open Science, Volume 3, Issue 1, January 2023, Pages 139-148, https://doi.org/10.1016/j.bpsgos.2021.12.011.

Background
Childhood sleep problems are common and among the most frequent and impairing comorbidities of childhood psychiatric disorders. In adults, sleep disturbances are heritable and show strong genetic associations with brain morphology; however, little is known about the genetic architecture of childhood sleep and potential etiological links between sleep, brain development, and pediatric-onset psychiatric symptoms.

Methods
Using data from the Adolescent Brain Cognitive Development Study (nPhenotype = 4428 for discovery/replication, nGenetics = 4728; age 9–10 years), we assessed phenotypic relationships, heritability, and genetic correlations between childhood sleep disturbances (insomnia, arousal, breathing, somnolence, hyperhidrosis, sleep-wake transitions), brain size (surface area, cortical thickness, volume), and dimensional psychopathology.

Results
Sleep disturbances showed widespread positive associations with multiple domains of childhood psychopathology; however, only insomnia showed replicable associations with smaller brain surface area. Among the sleep disturbances assessed, only insomnia showed significant heritability (h2SNP = 0.15, p < .05) and showed substantial genetic correlations with externalizing and attention-deficit/hyperactivity disorder symptomatology (rGs > 0.80, ps < .05). We found no evidence of genetic correlation between childhood insomnia and brain size. Furthermore, polygenic risk scores calculated from genome-wide association studies of adult insomnia and adult brain size did not predict childhood insomnia; instead, polygenic risk scores trained using attention-deficit/hyperactivity disorder genome-wide association studies predicted decreased surface area at baseline as well as insomnia and externalizing symptoms longitudinally.

Conclusions
Findings demonstrate a distinct genetic architecture underlying childhood insomnia and brain size and suggest genetic overlap between childhood insomnia and attention-deficit/hyperactivity disorder symptomatology. Additional research is needed to examine how genetic risk manifests in altered developmental trajectories and comorbid sleep/psychiatric symptoms across adolescence.

Characterizing different cognitive and neurobiological profiles in a community sample of children using a non-parametric approach: An fMRI study

Fekson VK, Michaeli T, Rosch KS, Schlagger BL, Horowitz-Kraus T. Characterizing different cognitive and neurobiological profiles in a community sample of children using a non-parametric approach: An fMRI study. Developmental Cognitive Neuroscience, Volume 60, April 2023, 101198, https://doi.org/10.1016/j.dcn.2023.101198

Executive Functions (EF) is an umbrella term for a set of mental processes geared towards goal-directed behavior supporting academic skills such as reading abilities. One of the brain’s functional networks implicated in EF is the Default Mode Network (DMN). The current study uses measures of inhibitory control, a main sub-function of EF, to create cognitive and neurobiological “inhibitory control profiles” and relate them to reading abilities in a large sample (N = 5055) of adolescents aged 9–10 from the Adolescent Brain Cognitive Development (ABCD) study. Using a Latent Profile Analysis (LPA) approach, data related to inhibitory control was divided into four inhibition classes. For each class, functional connectivity within the DMN was calculated from resting-state data, using a non-parametric algorithm for detecting group similarities. These inhibitory control profiles were then related to reading abilities. The four inhibitory control groups showed significantly different reading abilities, with neurobiologically different DMN segregation profiles for each class versus controls. The current study demonstrates that a community sample of children is not entirely homogeneous and is composed of different subgroups that can be differentiated both behaviorally/cognitively and neurobiologically, by focusing on inhibitory control and the DMN. Educational implications relating these results to reading abilities are noted.

Family- and neighborhood-level environmental associations with physical health conditions in 9- and 10-year-olds

Marshall AT, Adise S, Cardenas-Iniguez C, Hippolyte OK, Parchment CA, Villalobos TI, Wong LT, Cisneros CP, Kan EC, Palmer CE, Bodison SC, Herting MM, Sowell ER. Family- and neighborhood-level environmental associations with physical health conditions in 9- and 10-year-olds. Health Psychol. 2023 Jan 12. doi: 10.1037/hea0001254. Epub ahead of print. PMID: 36633989.

Objective: To determine how environmental factors are associated with physical health conditions in 9- to 10-year-old participants in the Adolescent Brain Cognitive Development (ABCD) Study, and how they are moderated by family-level socioeconomic status (SES).

Method: We performed cross-sectional analyses of 8,429 youth participants in the ABCD Study, in which nine physical health conditions (having underweight or overweight/obesity, not participating in sports activities, short sleep duration, high sleep disturbances, lack of vigorous and strengthening-related physical activity, miscellaneous medical problems, and traumatic brain injury) were regressed on three environmental factors [neighborhood disadvantage (area deprivation index [ADI]), risk of lead exposure, and concentrations of particulate matter 2.5 (PM2.5)] and their interaction with family-level SES (i.e., parent-reported annual household income). Environmental data were geocoded to participants’ primary residential addresses at 9- to 10-year-olds.

Results: Risk of lead exposure and ADI were positively associated with the odds of having overweight/obesity, not participating in sports activity, and short sleep durations. ADI was also positively associated with high sleep disturbances. PM2.5 was positively associated with the odds of having overweight/obesity and reduced vigorous physical activity. Family-level SES moderated relationships between ADI and both underweight and overweight/obesity, with high SES being associated with more pronounced changes given increased ADI.

Conclusions: Policymakers and public health officials must implement policies and remediation strategies to ensure children are free from exposure to neurotoxicant and environmental factors. Physical health conditions may be less of a product of an individual’s choices and more related to environmental influences.

A cognitive process modeling framework for the ABCD Study stop-signal task

Weigard A, Matzke D, Tanis C, Heathcote A. A cognitive process modeling framework for the ABCD study stop-signal task. Developmental Cognitive Neuroscience, Volume 59, 2023, 101191, ISSN 1878-9293, https://doi.org/10.1016/j.dcn.2022.101191.

The Adolescent Brain Cognitive Development (ABCD) Study is a longitudinal neuroimaging study of unprecedented scale that is in the process of following over 11,000 youth from middle childhood though age 20. However, a design feature of the study’s stop-signal task violates “context independence”, an assumption critical to current non-parametric methods for estimating stop-signal reaction time (SSRT), a key measure of inhibitory ability in the study. This has led some experts to call for the task to be changed and for previously collected data to be used with caution. We present a cognitive process modeling framework, the RDEX-ABCD model, that provides a parsimonious explanation for the impact of this design feature on “go” stimulus processing and successfully accounts for key behavioral trends in the ABCD data. Simulation studies using this model suggest that failing to account for the context independence violations in the ABCD design can lead to erroneous inferences in several realistic scenarios. However, we demonstrate that RDEX-ABCD effectively addresses these violations and can be used to accurately measure SSRT along with an array of additional mechanistic parameters of interest (e.g., attention to the stop signal, cognitive efficiency), advancing investigators’ ability to draw valid and nuanced inferences from ABCD data.

Why weight? Analytic approaches for large-scale population neuroscience data

Gard AM, Hyde LW, Heeringa S, West BT, Mitchell C. (In Press, 2023). Why weight? Analytic approaches for large-scale population neuroscience data. Developmental Cognitive Neuroscience, Available online 6 January 2023, 101196.

Population-based neuroimaging studies that feature complex sampling designs enable researchers to generalize their results more widely. However, several theoretical and analytic questions pose challenges to researchers interested in these data. The following is a resource for researchers interested in using population-based neuroimaging data by providing an overview of sampling designs and describing the differences between traditional model-based analyses and survey-oriented design-based analyses. To elucidate key concepts, we leverage data from the Adolescent Brain Cognitive Development℠ Study (ABCD Study®), a population-based sample of 11,878 9-10-year-olds in the United States. Analyses revealed modest sociodemographic discrepancies between the target population of 9-10-year-olds in the U.S. and both the recruited ABCD sample and analytic samples with usable structural and functional imaging data. In evaluating the associations between socioeconomic resources (i.e., constructs that are tightly linked to recruitment biases) and several metrics of brain development, we show that model-based approaches over-estimated the associations of household income and under-estimated the associations of caregiver education with total cortical volume and surface area, while comparable results were found in models predicting neural function during two fMRI task paradigms. We conclude with recommendations for ABCD Study® users and users of population-based neuroimaging cohorts more broadly.

Sex and age variations in the impact of puberty on cortical thickness and associations with internalizing symptoms and suicidal ideation in early adolescence

Wiglesworth A, Fiecas MB, Xu M, Neher AT, Padilla L, Carosella KA, Roediger DJ, Mueller BA, Luciana M, Klimes-Dougan B, Cullen KR. Sex and age variations in the impact of puberty on cortical thickness and associations with internalizing symptoms and suicidal ideation in early adolescence. Dev Cogn Neurosci. 2023 Jan 4;59:101195. doi: 10.1016/j.dcn.2022.101195. Epub ahead of print. PMID: 36621021.

Purpose: The childhood-to-adolescence transition is a notable period of change including pubertal development, neurodevelopment, and psychopathology onset, that occurs in divergent patterns between sexes. This study examined the effects of sex and puberty on cortical thickness (CT) in children and explored whether CT changes over time related to emergence of psychopathology in early adolescence.

Methods: We used longitudinal data (baseline ages 9-10 and Year 2 [Y2] ages 11-12) from the ABCD Study (n = 9985). Linear and penalized function-on-function regressions modeled the impact of puberty, as it interacts with sex, on CT. Focusing on regions that showed sex differences, linear and logistic regressions modeled associations between change in CT and internalizing problems and suicide ideation.

Results: We identified significant sex differences in the inverse relation between puberty and CT in fifteen primarily posterior brain regions. Nonlinear pubertal effects across age were identified in the fusiform, isthmus cingulate, paracentral, and precuneus. All effects were stronger for females relative to males during this developmental window. We did not identify associations between CT change and early adolescent clinical outcomes.

Conclusion: During this age range, puberty is most strongly associated with regional changes in CT in females, which may have implications for the later emergence of psychopathology.

Neuroanatomical correlates of genetic risk for obesity in children

Morys F, Yu E, Shishikura M, Paquola C, Vainik U, Nave G, Koellinger P, Gan-Or Z, Dagher A. Neuroanatomical correlates of genetic risk for obesity in children. Transl Psychiatry. 2023 Jan 3;13(1):1. doi: 10.1038/s41398-022-02301-5. PMID: 36596778.

Obesity has a strong genetic component, with up to 20% of variance in body mass index (BMI) being accounted for by common polygenic variation. Most genetic polymorphisms associated with BMI are related to genes expressed in the central nervous system. At the same time, higher BMI is associated with neurocognitive changes. However, the direct link between genetics of obesity and neurobehavioral mechanisms related to weight gain is missing. Here, we use a large sample of participants (n > 4000) from the Adolescent Brain Cognitive Development cohort to investigate how genetic risk for obesity, expressed as polygenic risk score for BMI (BMI-PRS), is related to brain and behavioral measures in adolescents. In a series of analyses, we show that BMI-PRS is related to lower cortical volume and thickness in the frontal and temporal areas, relative to age-expected values. Relatedly, using structural equation modeling, we find that lower overall cortical volume is associated with higher impulsivity, which in turn is related to an increase in BMI 1 year later. In sum, our study shows that obesity might partially stem from genetic risk as expressed in brain changes in the frontal and temporal brain areas, and changes in impulsivity.

General psychopathology factor (p-factor) prediction using resting-state functional connectivity and a scanner-generalization neural network

Hong J, Hwang J, Lee J-H. General psychopathology factor (p-factor) prediction using resting-state functional connectivity and a scanner-generalization neural network. Journal of Psychiatric Research. Volume 158, February 2023, Pages 114-125. https://doi.org/10.1016/j.jpsychires.2022.12.037

The general psychopathology factor (p-factor) represents shared variance across mental disorders based on psychopathologic symptoms. The Adolescent Brain Cognitive Development (ABCD) Study offers an unprecedented opportunity to investigate functional networks (FNs) from functional magnetic resonance imaging (fMRI) associated with the psychopathology of an adolescent cohort (n > 10,000). However, the heterogeneities associated with the use of multiple sites and multiple scanners in the ABCD Study need to be overcome to improve the prediction of the p-factor using fMRI. We proposed a scanner-generalization neural network (SGNN) to predict the individual p-factor by systematically reducing the scanner effect for resting-state functional connectivity (RSFC). We included 6905 adolescents from 18 sites whose fMRI data were collected using either Siemens or GE scanners. The p-factor was estimated based on the Child Behavior Checklist (CBCL) scores available in the ABCD study using exploratory factor analysis. We evaluated the Pearson’s correlation coefficients (CCs) for p-factor prediction via leave-one/two-site-out cross-validation (LOSOCV/LTSOCV) and identified important FNs from the weight features (WFs) of the SGNN. The CCs were higher for the SGNN than for alternative models when using both LOSOCV (0.1631 ± 0.0673 for the SGNN vs. 0.1497 ± 0.0710 for kernel ridge regression [KRR]; p < 0.05 from a two-tailed paired t-test) and LTSOCV (0.1469 ± 0.0381 for the SGNN vs. 0.1394 ± 0.0359 for KRR; p = 0.01). It was found that (a) the default-mode and dorsal attention FNs were important for p-factor prediction, and (b) the intra-visual FN was important for scanner generalization. We demonstrated the efficacy of our novel SGNN model for p-factor prediction while simultaneously eliminating scanner-related confounding effects for RSFC.

More Than a Learning Environment: School Climate as a Protective Factor for Child Neurodevelopment and Mental Health?

Thijssen S. More Than a Learning Environment: School Climate as a Protective Factor for Child Neurodevelopment and Mental Health? Biological Psychiatry, Commentary, Vol 8, Issue 1, P6-8, January 01, 2023. DOI:https://doi.org/10.1016/j.bpsc.2022.10.002

Compared with other mammals, human infants are born helpless and immature and are critically dependent upon their caregivers for their survival. Even as children mature, their caregivers continue to play an important role in fostering their health and in socializing their behaviors. Only few, therefore, would debate the proposition that a child’s home environment is significant in shaping their development. Indeed, in recent years, literature has been accumulating suggesting that family factors are associated with a child’s socioemotional development or mental health and that the brain may play an important role in explaining these associations (1). However, the home environment is not the only environment in which children spend a significant amount of their waking hours. Depending on their country of residence, from approximately 3 to 7 years of age onward, children spend about half of their day at school. It is surprising, therefore, that the association between school climate and child socioemotional and neurodevelopment is a relatively uncharted area of research. While research does show that a more positive school climate is associated with better socioemotional functioning (2), little is known about potential neural mechanisms. In the current issue of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Rakesh et al. (3) point out this gap in our knowledge and take an important first step in exploring associations between school climate and brain development.

2022
Neuroimaging profiling identifies distinct brain maturational subtypes of youth with mood and anxiety disorders

Ge, R., Sassi, R., Yatham, L.N. et al. Neuroimaging profiling identifies distinct brain maturational subtypes of youth with mood and anxiety disorders. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01925-9

Mood and anxiety disorders typically begin in adolescence and have overlapping clinical features but marked inter-individual variation in clinical presentation. The use of multimodal neuroimaging data may offer novel insights into the underlying brain mechanisms. We applied Heterogeneity Through Discriminative Analysis (HYDRA) to measures of regional brain morphometry, neurite density, and intracortical myelination to identify subtypes of youth, aged 9–10 years, with mood and anxiety disorders (N = 1931) compared to typically developing youth (N = 2823). We identified three subtypes that were robust to permutation testing and sample composition. Subtype 1 evidenced a pattern of imbalanced cortical-subcortical maturation compared to the typically developing group, with subcortical regions lagging behind prefrontal cortical thinning and myelination and greater cortical surface expansion globally. Subtype 2 displayed a pattern of delayed cortical maturation indicated by higher cortical thickness and lower cortical surface area expansion and myelination compared to the typically developing group. Subtype 3 showed evidence of atypical brain maturation involving globally lower cortical thickness and surface coupled with higher myelination and neural density. Subtype 1 had superior cognitive function in contrast to the other two subtypes that underperformed compared to the typically developing group. Higher levels of parental psychopathology, family conflict, and social adversity were common to all subtypes, with subtype 3 having the highest burden of adverse exposures. These analyses comprehensively characterize pre-adolescent mood and anxiety disorders, the biopsychosocial context in which they arise, and lay the foundation for the examination of the longitudinal evolution of the subtypes identified as the study sample transitions through adolescence.

Associations among body mass index, working memory performance, gray matter volume, and brain activation in healthy children

Zhang Y, Ji W, Jiang F, Wu F, Li G, Hu Y, Zhang W, Wang J, Fan X, Wei X, Manza P, Tomasi D, Volkow ND, Gao X, Wang GJ, Zhang Y. Associations among body mass index, working memory performance, gray matter volume, and brain activation in healthy children. Cereb Cortex. 2022 Dec 27:bhac507. doi: 10.1093/cercor/bhac507. Epub ahead of print. PMID: 36573454.

To investigate the neural mechanisms underlying the association between poorer working memory performance and higher body mass index (BMI) in children. We employed structural-(sMRI) and functional magnetic resonance imaging (fMRI) with a 2-back working memory task to examine brain abnormalities and their associations with BMI and working memory performance in 232 children with overweight/obesity (OW/OB) and 244 normal weight children (NW) from the Adolescent Brain Cognitive Development dataset. OW/OB had lower working memory accuracy, which was associated with higher BMI. They showed smaller gray matter (GM) volumes in the left superior frontal gyrus (SFG_L), dorsal anterior cingulate cortex, medial orbital frontal cortex, and medial superior frontal gyrus, which were associated with lower working memory accuracy. During the working memory task, OW/OB relative to NW showed weaker activation in the left superior temporal pole, amygdala, insula, and bilateral caudate. In addition, caudate activation mediated the relationship between higher BMI and lower working memory accuracy. Higher BMI is associated with smaller GM volumes and weaker brain activation in regions involved with working memory. Task-related caudate dysfunction may account for lower working memory accuracy in children with higher BMI.

Cyberbullying and Sleep Disturbance among Early Adolescents in the U.S.

Nagata JM, Yang JH, Singh G, Kiss O, Ganson KT, Testa A, Jackson DB, Baker FC. Cyberbullying and Sleep Disturbance among Early Adolescents in the U.S. Acad Pediatr. 2022 Dec 26:S1876-2859(22)00634-9. doi: 10.1016/j.acap.2022.12.007. Epub ahead of print. PMID: 36581100.

Objective: To determine the association between cyberbullying (victimization and perpetration) and sleep disturbance among a demographically diverse sample of 10-14-year-old early adolescents.

Methods: We analyzed cross-sectional data from the Adolescent Brain Cognitive Development (ABCD) Study (Year 2, 2018-2020) of early adolescents (10-14 years) in the U.S. Modified Poisson regression analyses examined the association between cyberbullying and self-reported and caregiver-reported sleep disturbance measures.

Results: In a sample of 9,443 adolescents (mean age 12.0 years, 47.9% female, 47.8% white), 5.1% reported cyberbullying victimization, and 0.5% reported cyberbullying perpetration in the past 12 months. Cyberbullying victimization in the past 12 months was associated with adolescent-reported trouble falling/staying asleep (risk ratio [RR] 1.87, 95% confidence interval [CI] 1.57, 2.21) and caregiver-reported overall sleep disturbance of the adolescent (RR: 1.16 95% CI 1.00, 1.33), in models adjusting for sociodemographic factors and screen time. Cyberbullying perpetration in the past 12 months was associated with trouble falling/staying asleep (RR 1.95, 95% CI 1.21, 3.15) and caregiver-reported overall sleep disturbance of the adolescent (RR: 1.49, 95% CI 1.00, 2.22).

Conclusions: Cyberbullying victimization and perpetration are associated with sleep disturbance in early adolescence. Digital media education and counseling for adolescents, parents, teachers, and clinicians could focus on guidance to prevent cyberbullying and support healthy sleep behavior for early adolescents.

Mediating effect of pubertal stages on the family environment and neurodevelopment: An open-data replication and multiverse analysis of an ABCD Study®

Demidenko MI, Kelly DP, Hardi FA, Ip KI, Lee S, Becker H, Hong S, Thijssen S, Luciana M, Keating DP. Mediating effect of pubertal stages on the family environment and neurodevelopment: An open-data replication and multiverse analysis of an ABCD Study®. Neuroimage Rep. 2022 Dec;2(4):100133. doi: 10.1016/j.ynirp.2022.100133. Epub 2022 Sep 18. PMID: 36561641; PMCID: PMC9770593.

Increasing evidence demonstrates that environmental factors meaningfully impact the development of the brain (Hyde et al., 2020; McEwen and Akil, 2020). Recent work from the Adolescent Brain Cognitive Development (ABCD) Study® suggests that puberty may indirectly account for some association between the family environment and brain structure and function (Thijssen et al., 2020). However, a limited number of large studies have evaluated what, how, and why environmental factors impact neurodevelopment. When these topics are investigated, there is typically inconsistent operationalization of variables between studies which may be measuring different aspects of the environment and thus different associations in the analytic models. Multiverse analyses (Steegen et al., 2016) are an efficacious technique for investigating the effect of different operationalizations of the same construct on underlying interpretations. While one of the assets of Thijssen et al. (2020) was its large sample from the ABCD data, the authors used an early release that contained 38% of the full ABCD sample. Then, the analyses used several ‘researcher degrees of freedom’ (Gelman and Loken, 2014) to operationalize key independent, mediating and dependent variables, including but not limited to, the use of a latent factor of preadolescents’ environment comprised of different subfactors, such as parental monitoring and child-reported family conflict. While latent factors can improve reliability of constructs, the nuances of each subfactor and measure that comprise the environment may be lost, making the latent factors difficult to interpret in the context of individual differences. This study extends the work of Thijssen et al. (2020) by evaluating the extent to which the analytic choices in their study affected their conclusions. In Aim 1, using the same variables and models, we replicate findings from the original study using the full sample in Release 3.0. Then, in Aim 2, using a multiverse analysis we extend findings by considering nine alternative operationalizations of family environment, three of puberty, and five of brain measures (total of 135 models) to evaluate the impact on conclusions from Aim 1. In these results, 90% of the directions of effects and 60% of the p-values (e.g. p > .05 and p < .05) across effects were comparable between the two studies. However, raters agreed that only 60% of the effects had replicated. Across the multiverse analyses, there was a degree of variability in beta estimates across the environmental variables, and lack of consensus between parent reported and child reported pubertal development for the indirect effects. This study demonstrates the challenge in defining which effects replicate, the nuance across environmental variables in the ABCD data, and the lack of consensus across parent and child reported puberty scales in youth.

Differences in cortical morphology and child internalizing or externalizing problems: Accounting for the co-occurrence

Zhang Y, Xu B, Kim HH, Muetzel R, Delaney SW, Tiemeier H. Differences in cortical morphology and child internalizing or externalizing problems: Accounting for the co-occurrence. JCPP Advances, Vol 2, Issue 4, e12114, December 2022, https://doi.org/10.1002/jcv2.12114

Background
Childhood internalizing and externalizing problems frequently co-occur. Many studies report neural correlates of either internalizing or externalizing problems, but few account for their co-occurrence. We aimed to assess specific cortical substrates of these psychiatric problems.

Methods
We used data from 9635 children aged 9–11 years in the baseline Adolescent Brain Cognitive Development Study. Internalizing and externalizing problem composite scales scores were derived from the Child Behavior Checklist. We standardized FreeSurfer-derived volumes of 68 cortical regions. We examined internalizing and externalizing problems separately and jointly (covariate-adjustment) in relation to cortical volumes, with and without adjusting for total brain volume (TBV) in multivariate linear regressions adjusted for demographics and multiple comparisons. We fit bifactor models to confirm the consistency of patterns exploring specific internalizing and specific externalizing problems. Sensitivity analyses included a vertex-wide analysis and a replication in another large population-based study.

Results
In separate TBV-unadjusted analyses, externalizing and internalizing problems were associated with smaller cortical volumes. If adjusted for externalizing behavior, however, larger cortical volumes were associated with internalizing problems, while smaller cortical volumes remained associated with externalizing problems after adjustment for internalizing problems. The bifactor model produced similar results, which were consistently replicated in another pre-adolescent neuroimaging sample. These associations likely represent global effects: adjusting for TBV rendered most associations non-significant. Vertex-wise analyses confirmed global patterns.

Conclusion
Our results suggest that internalizing and externalizing problems have globally opposing, and non-specific associations with cortical morphology in childhood, which are only apparent if analyses account for their co-occurrence.

Substance use patterns in 9 to 13-year-olds: Longitudinal findings from the Adolescent Brain Cognitive Development (ABCD) study

Sullivan RM, Wade NE, Wallace AL, Tapert SF, Pelham WE 3rd, Brown SA, Cloak CC, Feldstein Ewing SW, Madden PAF, Martz ME, Ross JM, Kaiver CM, Wirtz HG, Heitzeg MM, Lisdahl KM. Substance use patterns in 9 to 13-year-olds: Longitudinal findings from the Adolescent Brain Cognitive Development (ABCD) study. Drug Alcohol Depend Rep. 2022 Dec;5:100120. doi: 10.1016/j.dadr.2022.100120. Epub 2022 Nov 15. PMID: 36687306; PMCID: PMC9850746.

Background: Though largely substance-naïve at enrollment, a proportion of the youth in the Adolescent Brain Cognitive Development (ABCD) Study are expected to initiate substance use (SU) as they transition into later adolescence. With annual data from youth 9-13 years-old, this study aims to describe their SU patterns over time. Here, prevalence rates of use are reported, along with predicted odds of use while analyzing common risk-factors associated with youth SU.

Methods: The ABCD Study® enrolled 11,876 participants at Baseline (ages 9-10) and has followed them annually. Data through half of the third follow-up visit are available (ages 12-13; n = 6,251). SU descriptives for al psychoactive substances over time are outlined. General estimating equations (GEEs) assessed whether sociodemographic factors, internalizing and externalizing symptoms, and parental SU problems were associated with SU between Baseline and Y2 follow-up.

Results: Across time, alcohol and nicotine remain the most used substances. Yearly rates of any SU increased (past year use: 13.9% in Y1; 14% Y2, 18.4% Y3). Cumulatively, by Y3, 39.7% of the cohort reported experimenting (e.g., sipping alcohol) with SU within their lifetime, while 7.4% reported a “full use” (a full alcohol drink, nicotine use, cannabis use, or any other SU) in their lifetime (past-year: 1.9% alcohol, 2.1% nicotine, 1.1% cannabis, 1.2% other substances). GEEs revealed ongoing longitudinal associations between sociodemographic factors, greater externalizing symptoms, and parental drug problems with increased odds of initiating SU.

Conclusions: As ABCD participants transition into their teenage years, the cohort is initiating SU at increasing (though still low) rates.

Gender identity-based disparities in self-injurious thoughts and behaviors among pre-teens in the United States

Randall AB, van der Star A, Pennesi JL, Siegel JA, Blashill AJ. Gender identity-based disparities in self-injurious thoughts and behaviors among pre-teens in the United States. Suicide Life Threat Behav. 2022 Dec 23. doi: 10.1111/sltb.12937. Epub ahead of print. PMID: 36562588.

Introduction: Transgender individuals are at heightened risk for self-injurious thoughts and behaviors (SITBs). Evidence suggests that middle childhood-aged transgender individuals experience elevated rates of non-suicidal self-injury (NSSI) and passive suicidal ideation (SI), compared to cisgender children. Little is known about gender identity-based disparities in SI more broadly and suicidal behavior (SB) in children aged 9 and 10. The aim of this study was to examine gender identity-based disparities in SITBs among children in middle childhood (pre-teens) in a US-based sample.

Methods: Using data from the 3.0 baseline release of the Adolescent Brain Cognitive Development (ABCD) study, logistic regression models, unadjusted and adjusted for covariates, were performed to examine gender identity-based disparities in SITBs.

Results: In a model adjusted for birth sex, race/ethnicity, and household income, transgender children were at significantly higher odds for current (adjusted odds ratio [AOR] = 6.34) but not lifetime NSSI compared with cisgender children. Transgender children were at significantly higher odds for current and lifetime SI (AOR = 13.03; AOR = 5.39, respectively) and SB (AOR = 14.21; AOR = 12.64, respectively) compared with cisgender children.

Conclusions: Gender identity-based disparities in SITBs may be present as early as age 9 and 10, demonstrating the need for SITB prevention and intervention efforts specific to transgender children.

Lower Daily Steps among U.S. Adolescents during the COVID-19 Pandemic: Objective Findings from the Adolescent Brain Cognitive Development Study

Nagata JM, Yu J, Dooley EE, Baker FC, Alsamman S, Wing D, Ganson KT, Gabriel KP. Lower Daily Steps among U.S. Adolescents during the COVID-19 Pandemic: Objective Findings from the Adolescent Brain Cognitive Development Study. Prev Med Rep. 2022 Dec 19:102095. doi: 10.1016/j.pmedr.2022.102095. Epub ahead of print. PMCID: PMC9762097.

Introduction
While the psychological and physical benefits of physical activity are well established, less than one quarter of US adolescents meet the physical activity guidelines recommended by the US Department of Health and Human Services (60 minutes per day, seven days per week) (U.S. Department of Health and Human Services, 2018). Furthermore, recent studies suggest that with the onset of the COVID-19 pandemic, the proportion of adolescents meeting these guidelines fell to 9% based on self-report (Nagata et al., 2022a). However, report-based physical activity measures are prone to measurement error (e.g., incomplete quantification) and information biases (e.g., recall). Objective measures such as step counts provide a continuous indicator of activity over multiple days. One worldwide study suggested a decrease in daily step count in adults early in the pandemic (Tison et al., 2020), but there is a paucity of objective data in adolescents in the US. The aim of this study was to quantify differences in step count before and during the COVID-19 pandemic among a demographically diverse national sample of adolescents.

Methods
Cross-sectional data from Year 2 (2018-2020) of the Adolescent Brain Cognitive Development (ABCD) Study were analyzed in 2022. The sample consisted of 4,955 adolescents (total of 71,833 observations) ages 11-14 with 50.0% female and 41.3% racial/ethnic minorities. Centralized institutional review board (IRB) approval was obtained from the University of California, San Diego. Written informed consent and assent were obtained from a parent/guardian and the child, respectively, to participate in the ABCD study. Steps per day (steps d-1) were collected via Fitbit Charge (Fitbit Inc., San Francisco, CA) over a single continuous three-week (21-day) period at the time of their Year 2 annual questionnaire. Others have shown that Fitbit provides accurate and consistent measurements of daily step count, an estimate of accumulated physical activity, in adolescents over long periods of time (Bagot et al., 2018, Godino et al., 2020). We followed best practices to extract, filter, and process data established by the ABCD Study (Bagot et al., 2018, Godino et al., 2020). We included all days with >599 minutes of waking wear within each participant’s three-week study protocol, collected between November 2018 to November 2020. Generalized estimating equations were used to compare repeated measures of daily steps d-1 for pre- (3/13/2019-11/27/2019) and peri- (3/13/2020-11/27/2020) pandemic, adjusting for sex, age, race/ethnicity, household income, month, and study site. Analyses were conducted in 2022 using Stata 16.1.

Results
Total steps d-1 by month are shown in Figure 1 a. The largest pre- to peri-pandemic differences in daily steps appeared during the typical school months (e.g., non-summer months). Total steps d-1by day of the week are shown in Figure 1b. The largest pre- to peri-pandemic differences in steps per day appeared during weekdays. Using generalized estimating equations controlling for potential confounders, the peri-pandemic period was associated with 2,188 (95% confidence interval 1,960-2,415) fewer steps per day (20.8 % lower) than the pre-pandemic period (9,625 average daily steps pre-pandemic).

Discussion
In this large, national sample of early adolescents, participants assessed in the first year of the COVID-19 pandemic had 20.8% fewer average total daily steps than did participants in the pre-pandemic period. This difference in daily steps for adolescents is even greater than the mean difference of -1432 steps d-1 previously reported in adults early in the pandemic (Tison et al., 2020). The largest difference in steps was apparent during weekdays and non-summer months, typically periods of schooling. This finding likely reflects the impact of school closures, cancellation of sports seasons and in-person physical education classes on adolescent physical activity (Nagata et al., 2022a, 2022b). Limitations of this study include its cross-sectional nature and the possibility for unmeasured confounders, although we controlled for site, month, and sociodemographic factors. Future studies should explore ongoing trends in daily steps among adolescents after resumption of in-person schooling. Given the beneficial effects of physical activity on physical, mental, and social health, promoting physical activity after initial reductions during the pandemic is critical for the current generation of adolescents.

Machine learning approaches linking brain function to behavior in the ABCD STOP task

Yuan D, Hahn S, Allgaier N, Owens MM, Chaarani B, Potter A, Garavan H. Machine learning approaches linking brain function to behavior in the ABCD STOP task. Hum Brain Mapp. 2022 Dec 19. doi: 10.1002/hbm.26172. Epub ahead of print. PMID: 36534603.

The stop-signal task (SST) is one of the most common fMRI tasks of response inhibition, and its performance measure, the stop-signal reaction-time (SSRT), is broadly used as a measure of cognitive control processes. The neurobiology underlying individual or clinical differences in response inhibition remain unclear, consistent with the general pattern of quite modest brain-behavior associations that have been recently reported in well-powered large-sample studies. Here, we investigated the potential of multivariate, machine learning (ML) methods to improve the estimation of individual differences in SSRT with multimodal structural and functional region of interest-level neuroimaging data from 9- to 11-year-olds children in the ABCD Study. Six ML algorithms were assessed across modalities and fMRI tasks. We verified that SST activation performed best in predicting SSRT among multiple modalities including morphological MRI (cortical surface area/thickness), diffusion tensor imaging, and fMRI task activations, and then showed that SST activation explained 12% of the variance in SSRT using cross-validation and out-of-sample lockbox data sets (n = 7298). Brain regions that were more active during the task and that showed more interindividual variation in activation were better at capturing individual differences in performance on the task, but this was only true for activations when successfully inhibiting. Cortical regions outperformed subcortical areas in explaining individual differences but the two hemispheres performed equally well. These results demonstrate that the detection of reproducible links between brain function and performance can be improved with multivariate approaches and give insight into a number of brain systems contributing to individual differences in this fundamental cognitive control process.

Genetic risk of AUDs and childhood impulsivity: Examining the role of parenting and family environment

Su J, Trevino A, Jamil B, Aliev F. Genetic risk of AUDs and childhood impulsivity: Examining the role of parenting and family environment. Dev Psychopathol. 2022 Dec 16:1-14. doi: 10.1017/S095457942200092X. Epub ahead of print. PMID: 36523258.

This study examined the independent and interactive effects of genetic risk for alcohol use disorder (AUD), parenting behaviors, and family environment on childhood impulsivity. Data were drawn from White (n = 5,991), Black/African American (n = 1,693), and Hispanic/Latino (n = 2,118) youth who completed the baseline assessment (age 9-10) and had genotypic data available from the Adolescent Brain Cognitive Development Study. Participants completed questionnaires and provided saliva or blood samples for genotyping. Results indicated no significant main effects of AUD genome-wide polygenic scores (AUD-PRS) on childhood impulsivity as measured by the UPPS-P scale across racial/ethnic groups. In general, parental monitoring and parental acceptance were associated with lower impulsivity; family conflict was associated with higher impulsivity. There was an interaction effect between AUD-PRS and family conflict, such that family conflict exacerbated the association between AUD-PRS and positive urgency, only among Black/African American youth. This was the only significant interaction effect detected from a total of 45 tests (five impulsivity dimensions, three subsamples, and three family factors), and thus may be a false positive and needs to be replicated. These findings highlight the important role of parenting behaviors and family conflict in relation to impulsivity among children.

Access to quality health resources and environmental toxins affect the relationship between brain structure and BMI in a sample of pre and early adolescents

Adise S, Marshall AT, Kan E, Sowell ER. Access to quality health resources and environmental toxins affect the relationship between brain structure and BMI in a sample of pre and early adolescents. Front Public Health. 2022 Dec 15;10:1061049. doi: 10.3389/fpubh.2022.1061049. PMID: 36589997; PMCID: PMC9797683.

Background: Environmental resources are related to childhood obesity risk and altered brain development, but whether these relationships are stable or if they have sustained impact is unknown. Here, we utilized a multidimensional index of childhood neighborhood conditions to compare the influence of various social and environmental disparities (SED) on body mass index (BMI)-brain relationships over a 2-year period in early adolescence.

Methods: Data were gathered the Adolescent Brain Cognitive Development Study® (n = 2,970, 49.8% female, 69.1% White, no siblings). Structure magnetic resonance imaging (sMRI), anthropometrics, and demographic information were collected at baseline (9/10-years-old) and the 2-year-follow-up (11/12-years-old). Region of interest (ROIs; 68 cortical, 18 subcortical) estimates of cortical thickness and subcortical volume were extracted from sMRI T1w images using the Desikan atlas. Residential addresses at baseline were used to obtain geocoded estimates of SEDs from 3 domains of childhood opportunity index (COI): healthy environment (COIHE), social/economic (COISE), and education (COIED). Nested, random-effects mixed models were conducted to evaluate relationships of BMI with (1) ROI * COI[domain] and (2) ROI * COI[domain] * Time. Models controlled for sex, race, ethnicity, puberty, and the other two COI domains of non-interest, allowing us to estimate the unique variance explained by each domain and its interaction with ROI and time.

Results: Youth living in areas with lower COISE and COIED scores were heavier at the 2-year follow-up than baseline and exhibited greater thinning in the bilateral occipital cortex between visits. Lower COISE scores corresponded with larger volume of the bilateral caudate and greater BMI at the 2-year follow-up. COIHE scores showed the greatest associations (n = 20 ROIs) with brain-BMI relationships: youth living in areas with lower COIHE had thinner cortices in prefrontal regions and larger volumes of the left pallidum and Ventral DC. Time did not moderate the COIHE x ROI interaction for any brain region during the examined 2-year period. Findings were independent of family income (i.e., income-to-needs).

Conclusion: Collectively our findings demonstrate that neighborhood SEDs for health-promoting resources play a particularly important role in moderating relationships between brain and BMI in early adolescence regardless of family-level financial resources.

Adherence to 24-Hour Movement Recommendations and Health Indicators in Early Adolescence: Cross-Sectional and Longitudinal Associations in the Adolescent Brain Cognitive Development Study

Fung H, Yeo BTT, Chen C, Lo JC, Chee MWL, Ong JL. Adherence to 24-Hour Movement Recommendations and Health Indicators in Early Adolescence: Cross-Sectional and Longitudinal Associations in the Adolescent Brain Cognitive Development Study. J Adolesc Health. 2022 Dec 15:S1054-139X(22)00718-2. doi: 10.1016/j.jadohealth.2022.10.019. Epub ahead of print. PMID: 36528521.

Purpose: Adherence to 24-hour movement guidelines of ≥60 minutes of physical activity, ≤2 hours of screen time, and 9-11 hours of sleep has been shown to benefit cognitive, physical, and psychosocial health in children and young adolescents aged 5-13 years. However, these findings have mostly been based on cross-sectional studies or relatively small samples and the associations between adherence to guidelines and brain structure remain to be evaluated.

Methods: Data from the Adolescent Brain Cognitive Development℠ (ABCD) study of 10,574 early adolescents aged 9-14 years from September 2016 to January 2021 were used to examine whether adherence to 24-hour movement guidelines benefits cognition (general cognitive ability, executive function, and learning/memory assessed by the National Institutes of Health Toolbox neurocognitive battery), body mass index, psychosocial health (internalizing, externalizing, and total problems from the parent-reported Child Behavior Checklist), and magnetic resonance imaging-derived brain morphometric measures at baseline (T1), ∼2 years later (T2), and longitudinally from T1 to T2 (T2-T1). Multivariable linear mixed models were used, with adjustments for sociodemographic confounders. Time elapsed and T1 outcome measures were also controlled for in longitudinal models.

Results: Better cognitive scores, fewer behavioral problems, lower adiposity levels, and greater gray matter volumes were observed in those who met both sleep and screen time recommendations compared to those who met none. Longitudinal follow-up further supports these findings; participants who met both recommendations at T1 and T2 evidenced better outcome measures than those who met none.

Discussion: These findings support consideration of integrated rather than isolated movement recommendations across the day in early adolescence for better cognitive, physical and psychosocial health. Although the associations between physical activity and health indicators were less consistent in this study, the significant findings from sleep and screen time demonstrate the importance of considering movement recommendations in an integrated rather than isolated manner for adolescent health. It is recommended that movement behaviors be simultaneously targeted for better developmental outcomes.

Rare copy number variants in males and females with childhood attention-deficit/hyperactivity disorder

Jung, B., Ahn, K., Justice, C. et al. Rare copy number variants in males and females with childhood attention-deficit/hyperactivity disorder. Mol Psychiatry (2022), . https://doi.org/10.1038/s41380-022-01906-y

While childhood attention-deficit/hyperactivity disorder (ADHD) is more prevalent in males than females, genetic contributors to this effect have not been established. Here, we explore sex differences in the contribution of common and/or rare genetic variants to ADHD. Participants were from the Adolescent Brain and Cognitive Development study (N = 1253 youth meeting DSM-5 criteria for ADHD [mean age = 11.46 years [SD = 0.87]; 31% female] and 5577 unaffected individuals [mean age = 11.42 years [SD = 0.89]; 50% female], overall 66% White, non-Hispanic (WNH), 19% Black/African American, and 15% other races. Logistic regression tested for interactions between sex (defined genotypically) and both rare copy number variants (CNV) and polygenic (common variant) risk in association with ADHD. There was a significant interaction between sex and the presence of a CNV deletion larger than 200 kb, both in the entire cohort (β = −0.74, CI = [−1.27 to −0.20], FDR-corrected p = 0.048) and, at nominal significance levels in the WNH ancestry subcohort (β = −0.86, CI = [−1.51 to −0.20], p = 0.010). Additionally, the number of deleted genes interacted with sex in association with ADHD (whole cohort. β = −0.13, CI = [−0.23 to −0.029], FDR-corrected p = 0.048; WNH. β = −0.17, CI = [−0.29 to −0.050], FDR-corrected p = 0.044) as did the total length of CNV deletions (whole cohort. β = −0.12, CI = [−0.19 to −0.044], FDR-corrected p = 0.028; WNH. β = −0.17, CI = [−0.28 to −0.061], FDR-corrected p = 0.034). This sex effect was driven by increased odds of childhood ADHD for females but not males in the presence of CNV deletions. No similar sex effect was found for CNV duplications or polygenic risk scores. The association between CNV deletions and ADHD was partially mediated by measures of cognitive flexibility. In summary, CNV deletions were associated with increased odds for childhood ADHD in females, but not males.

Modeling environment through a general exposome factor in two independent adolescent cohorts

Moore TM, Visoki E, Argabright ST, Didomenico GE, Sotelo I, Wortzel JD, Naeem A, Gur RC, Gur RE, Warrier V, Guloksuz S, Barzilay R. Modeling environment through a general exposome factor in two independent adolescent cohorts. Exposome. 2022 Dec 14;2(1):osac010. doi: 10.1093/exposome/osac010. PMID: 36606125; PMCID: PMC9798749.

Exposures to perinatal, familial, social, and physical environmental stimuli can have substantial effects on human development. We aimed to generate a single measure that capture’s the complex network structure of the environment (ie, exposome) using multi-level data (participant’s report, parent report, and geocoded measures) of environmental exposures (primarily from the psychosocial environment) in two independent adolescent cohorts: The Adolescent Brain Cognitive Development Study (ABCD Study, N = 11 235; mean age, 10.9 years; 47.7% females) and an age- and sex-matched sample from the Philadelphia Neurodevelopmental Cohort (PNC, N = 4993). We conducted a series of data-driven iterative factor analyses and bifactor modeling in the ABCD Study, reducing dimensionality from 348 variables tapping to environment to six orthogonal exposome subfactors and a general (adverse) exposome factor. The general exposome factor was associated with overall psychopathology (B = 0.28, 95% CI, 0.26-0.3) and key health-related outcomes: obesity (odds ratio [OR] , 1.4; 95% CI, 1.3-1.5) and advanced pubertal development (OR, 1.3; 95% CI, 1.2-1.5). A similar approach in PNC reduced dimensionality of environment from 29 variables to 4 exposome subfactors and a general exposome factor. PNC analyses yielded consistent associations of the general exposome factor with psychopathology (B = 0.15; 95% CI, 0.13-0.17), obesity (OR, 1.4; 95% CI, 1.3-1.6), and advanced pubertal development (OR, 1.3; 95% CI, 1-1.6). In both cohorts, inclusion of exposome factors greatly increased variance explained in overall psychopathology compared with models relying solely on demographics and parental education (from <4% to >38% in ABCD; from <4% to >18.5% in PNC). Findings suggest that a general exposome factor capturing multi-level environmental exposures can be derived and can consistently explain variance in youth’s mental and general health.

Screen Time and Obsessive-Compulsive Disorder Among Children 9–10 Years Old: A Prospective Cohort Study

Nagata JM, Chu J, Zamora G, Ganson KT, Testa A, Jackson DB, Costello CR, Murray SB, Baker FC. Screen Time and Obsessive-Compulsive Disorder Among Children 9-10 Years Old: A Prospective Cohort Study. J Adolesc Health. 2022 Dec 12:S1054-139X(22)00722-4. doi: 10.1016/j.jadohealth.2022.10.023. Epub ahead of print. PMID: 36517380.

Purpose: The aim of this study is to determine the prospective associations between baseline screen time and obsessive-compulsive disorder (OCD) at 2-year follow-up in a national (United States) cohort of 9- to 10-year-old children.

Methods: We analyzed prospective cohort data from the Adolescent Brain Cognitive Development study (n = 9,208). Logistic regression analyses were used to determine the associations between baseline self-reported screen time (exposure) and OCD, based on the Kiddie Schedule for Affective Disorders and Schizophrenia (outcome), at 2-year-follow-up, adjusting for race/ethnicity, sex, household income, parent education, family history of psychopathology, and study site, excluding participants with baseline OCD.

Results: The sample was 48.9% female and racially and ethnically diverse (43.5% non-White). Each additional hour of total screen time was prospectively associated with 1.05 higher odds of OCD at 2-year follow-up (95% confidence interval [CI] 1.01-1.09). For specific screen time modalities, each additional hour of playing video games (adjusted odds ratio 1.15, 95% CI 1.03-1.28) and watching videos (adjusted odds ratio 1.11, 95% CI 1.01-1.23) was associated with a subsequent OCD diagnosis.

Conclusion: Video games and watching videos are prospectively associated with new-onset OCD in early adolescents. Future research should examine mechanisms linking these specific screen modalities to OCD development to inform future prevention and intervention efforts.

A genetically informed Registered Report on adverse childhood experiences and mental health

Baldwin, J.R., Sallis, H.M., Schoeler, T. et al. A genetically informed Registered Report on adverse childhood experiences and mental health. Nat Hum Behav (2022). https://doi.org/10.1038/s41562-022-01482-9

Children who experience adversities have an elevated risk of mental health problems. However, the extent to which adverse childhood experiences (ACEs) cause mental health problems remains unclear, as previous associations may partly reflect genetic confounding. In this Registered Report, we used DNA from 11,407 children from the United Kingdom and the United States to investigate gene–environment correlations and genetic confounding of the associations between ACEs and mental health. Regarding gene–environment correlations, children with higher polygenic scores for mental health problems had a small increase in odds of ACEs. Regarding genetic confounding, elevated risk of mental health problems in children exposed to ACEs was at least partially due to pre-existing genetic risk. However, some ACEs (such as childhood maltreatment and parental mental illness) remained associated with mental health problems independent of genetic confounding. These findings suggest that interventions addressing heritable psychiatric vulnerabilities in children exposed to ACEs may help reduce their risk of mental health problems.

Morphometric dis-similarity between cortical and subcortical areas underlies cognitive function and psychiatric symptomatology: a preadolescence study from ABCD

Wu X, Palaniyappan L, Yu G, Zhang K, Seidlitz J, Liu Z, Kong X, Schumann G, Feng J, Sahakian BJ, Robbins TW, Bullmore E, Zhang J. Morphometric dis-similarity between cortical and subcortical areas underlies cognitive function and psychiatric symptomatology: a preadolescence study from ABCD. Mol Psychiatry. 2022 Dec 6. doi: 10.1038/s41380-022-01896-x. Epub ahead of print. PMID: 36473996.

Preadolescence is a critical period characterized by dramatic morphological changes and accelerated cortico-subcortical development. Moreover, the coordinated development of cortical and subcortical regions underlies the emerging cognitive functions during this period. Deviations in this maturational coordination may underlie various psychiatric disorders that begin during preadolescence, but to date these deviations remain largely uncharted. We constructed a comprehensive whole-brain morphometric similarity network (MSN) from 17 neuroimaging modalities in a large preadolescence sample (N = 8908) from Adolescent Brain Cognitive Development (ABCD) study and investigated its association with 10 cognitive subscales and 27 psychiatric subscales or diagnoses. Based on the MSNs, each brain was clustered into five modules with distinct cytoarchitecture and evolutionary relevance. While morphometric correlation was positive within modules, it was negative between modules, especially between isocortical and paralimbic/subcortical modules; this developmental dissimilarity was genetically linked to synapse and neurogenesis. The cortico-subcortical dissimilarity becomes more pronounced longitudinally in healthy children, reflecting developmental differentiation of segregated cytoarchitectonic areas. Higher cortico-subcortical dissimilarity (between the isocortical and paralimbic/subcortical modules) were related to better cognitive performance. In comparison, children with poor modular differentiation between cortex and subcortex displayed higher burden of externalizing and internalizing symptoms. These results highlighted cortical-subcortical morphometric dissimilarity as a dynamic maturational marker of cognitive and psychiatric status during the preadolescent stage and provided insights into brain development.

Relating neighborhood deprivation to childhood obesity in the ABCD study: Evidence for theories of neuroinflammation and neuronal stress

Adise S, Marshall AT, Kan E, Gonzalez MR, Sowell ER. Relating neighborhood deprivation to childhood obesity in the ABCD study: Evidence for theories of neuroinflammation and neuronal stress. Health Psychol. 2022 Dec 5. doi: 10.1037/hea0001250. Epub ahead of print. PMID: 36469439.

Objective: We evaluated whether relationships between area deprivation (ADI), body mass index (BMI) and brain structure (e.g., cortical thickness, subcortical volume) during preadolescence supported the immunologic model of self-regulation failure (NI) and/or neuronal stress (NS) theories of overeating. The NI theory proposes that ADI causes structural alteration in the brain due to the neuroinflammatory effects of overeating unhealthy foods. The NS theory proposes that ADI-related stress negatively impacts brain structure, which causes stress-related overeating and subsequent obesity.

Method: Data were gathered from the Adolescent Brain Cognitive Development Study (9 to 12 years old; n = 3,087, 51% male). Linear mixed-effects models identified brain regions that were associated with both ADI and BMI; longitudinal associations were evaluated with mediation models. The NI model included ADI and BMI at 9 to 10 years old and brain data at 11 to 12 years old. The NS model included ADI and brain data at 9 to 10 years old and BMI at 11 to 12 years old.

Results: BMI at 9 to 10 years old partially mediated the relationship between ADI and ventral diencephalon (DC) volume at 11 to 12 years old. Additionally, the ventral DC at 9 to 10 years old partially mediated the relationship between ADI and BMI at 11 to 12 years old, even in youth who at baseline, were of a healthy weight. Results were unchanged when controlling for differences in brain structure and weight across the 2-years.

Conclusion: Greater area deprivation may indicate fewer access to resources that support healthy development, like nutritious food and nonstressful environments. Our findings provide evidence in support of the NI and NS theories of overeating, specifically, with greater ADI influencing health outcomes of obesity via brain structure alterations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Associations between socioeconomic gradients and racial disparities in preadolescent brain outcomes

Isaiah A, Ernst TM, Liang H, Ryan M, Cunningham E, Rodriguez PJ, Menken M, Kaschak D, Guihen C, Reeves G, Lever N, Edwards SM, Chang L. Associations between socioeconomic gradients and racial disparities in preadolescent brain outcomes. Pediatr Res. 2022 Dec 1. doi: 10.1038/s41390-022-02399-9. Epub ahead of print. PMID: 36456690.

Background: The aim of this study was to determine the extent to which socioeconomic characteristics of the home and neighborhood are associated with racial inequalities in brain outcomes.

Methods: We performed a cross-sectional analysis of the baseline dataset (v.2.0.1) from the Adolescent Brain and Cognitive Development (ABCD) Study. Cognitive performance was assessed using the National Institutes of Health Toolbox (NIH-TB) cognitive battery. Standard socioeconomic indicators of the family and neighborhood were derived from census-related statistics. Cortical morphometric measures included MRI-derived thickness, area, and volume.

Results: 9638 children were included. Each NIH-TB cognitive measure was negatively associated with household and neighborhood socioeconomic characteristics. Differences in cognitive scores between Black or Hispanic children and other racial groups were mitigated by higher household income. Most children from lowest-income families or residents in impoverished neighborhoods were Black or Hispanic. These disparities were associated with racial differences in NIH-TB measures and mediated by smaller cortical brain volumes.

Conclusions: Neighborhood socioeconomic characteristics are associated with racial differences in preadolescent brain outcomes and mitigated by greater household income. Household income mediates racial differences more strongly than neighborhood-level socioeconomic indicators in brain outcomes. Highlighting these socioeconomic risks may direct focused policy-based interventions such as allocation of community resources to ensure equitable brain outcomes in children.

Impact: Neighborhood socioeconomic characteristics are associated with racial differences in preadolescent brain outcomes and mitigated by greater household income. Household income mediates racial differences more strongly than neighborhood-level socioeconomic indicators in brain outcomes. Highlighting these disparities related to socioeconomic risks may direct focused policy-based interventions such as allocation of community resources to ensure equitable brain outcomes in children.

Sensory Over-Responsivity: A Feature of Childhood Psychiatric Illness Associated with Altered Functional Connectivity of Sensory Networks

Schwarzlose RF, Tillman R, Hoyniak CP, Luby J, Barch DM. Sensory Over-Responsivity: A Feature of Childhood Psychiatric Illness Associated with Altered Functional Connectivity of Sensory Networks. Biological Psychiatry. Volume 93, Issue 1, 1 January 2023, Pages 92-101. https://doi.org/10.1016/j.biopsych.2022.09.004.

Background
Sensory over-responsivity (SOR) is recognized as a common feature of autism spectrum disorder. However, SOR is also common among typically developing children, in whom it is associated with elevated levels of psychiatric symptoms. The clinical significance and neurocognitive bases of SOR in these children remain poorly understood and actively debated.

Methods
This study used linear mixed-effects models to identify psychiatric symptoms and network-level functional connectivity (FC) differences associated with parent-reported SOR in the Adolescent Brain Cognitive Development (ABCD) Study, a large community sample (9 to 12 years of age) (N = 11,210).

Results
Children with SOR constituted 18% of the overall sample but comprised more than half of the children with internalizing or externalizing scores in the clinical range. Controlling for autistic traits, both mild and severe SOR were associated with greater concurrent symptoms of depression, anxiety, obsessive-compulsive disorder, and attention-deficit/hyperactivity disorder. Controlling for psychiatric symptoms and autistic traits, SOR predicted increased anxiety, attention-deficit/hyperactivity disorder, and prodromal psychosis symptoms 1 year later and was associated with FC differences in brain networks supporting sensory and salience processing in datasets collected 2 years apart. Differences included reduced FC within and between sensorimotor networks, enhanced sensorimotor-salience FC, and altered FC between sensory networks and bilateral hippocampi.

Conclusions
SOR is a common, clinically relevant feature of childhood psychiatric illness that provides unique predictive information about risk. It is associated with differences in brain networks that subserve tactile processing, implicating a neural basis for sensory differences in affected children.

A multidimensional approach to understanding the emergence of sex differences in internalizing symptoms in adolescence

Serio B, Kohler R, Ye F, Lichenstein SD, Yip SW. A multidimensional approach to understanding the emergence of sex differences in internalizing symptoms in adolescence. Dev Cogn Neurosci. 2022 Nov 28;58:101182. doi: 10.1016/j.dcn.2022.101182. Epub ahead of print. PMID: 36495789.

Women are more vulnerable to internalizing disorders (e.g., depression and anxiety). This study took an integrative developmental approach to investigate multidimensional factors associated with the emergence of sex differences in internalizing symptoms, using data from the Adolescent Brain Cognitive Development (ABCD) study. Indices of sex hormone levels (dehydroepiandrosterone, testosterone, and estradiol), physical pubertal development, task-based functional brain activity, family conflict, and internalizing symptoms were drawn from the ABCD study’s baseline sample (9- to 10-year-old; N = 11,844). Principal component analysis served as a data-driven dimensionality reduction technique on the internalizing subscales to yield a single robust measure of internalizing symptoms. Moderated mediation analyses assessed whether associations between known risk factors and internalizing symptoms vary by sex. Results revealed direct and indirect effects of physical pubertal development on internalizing symptoms through family conflict across sexes. No effects were found of sex hormone levels or amygdala response to fearful faces on internalizing symptoms. Females did not report overall greater internalizing symptoms relative to males, suggesting that internalizing symptoms have not yet begun to increase in females at this age. Findings provide an essential baseline for future longitudinal research on the endocrine, neurocognitive, and psychosocial factors associated with sex differences in internalizing symptoms.

Adverse childhood experiences and early adolescent cyberbullying in the United States

Nagata JM, Trompeter N, Singh G, Raney J, Ganson KT, Testa A, Jackson DB, Murray SB, Baker FC. Adverse childhood experiences and early adolescent cyberbullying in the United States. J Adolesc. 2022 Nov 28. doi: 10.1002/jad.12124. Epub ahead of print. PMID: 36443937.

Introduction: With the increasing use of social media and online platforms among adolescents, the relationship between traumatic life events and cyberbullying remains unclear. This study aimed to determine the associations between adverse childhood experiences (ACEs) and cyberbullying victimization among a racially/ethnically and socioeconomically diverse sample of early adolescents.

Methods: We analyzed longitudinal data from 10,317 participants in the Adolescent Brain Cognitive Development (ABCD) study, baseline (2016-2018, ages 9-10 years) to Year 2. Logistic regression analyses were used to estimate associations between ACEs and cyberbullying victimization, adjusting for sex, race/ethnicity, country of birth, household income, parental education, and study site.

Results: In the sample (48.7% female, 46.0% racial/ethnic minority), 81.3% of early adolescents reported at least one ACE, and 9.6% reported cyberbullying victimization. In general, there was a dose-response relationship between the number of ACEs and cyberbullying victimization, as two (adjusted odds ratio [AOR]: 1.45, 95% confidence interval [CI]: 1.13-1.85), three (AOR: 2.08, 95% CI: 1.57-2.74), and four or more (AOR: 2.37, 95% CI: 1.61-3.49) ACEs were associated with cyberbullying victimization in adjusted models. In models examining the specific type of ACE, sexual abuse (AOR: 2.27, 95% CI: 1.26-4.11), physical neglect (AOR: 1.61, 95% CI: 1.24-2.09), and household mental health problems (AOR: 1.39, 95% CI: 1.18-1.65) had the strongest associations with cyberbullying victimization.

Conclusion: Adolescents who have experienced ACEs are at greater risk for experiencing cyberbullying. Interventions to prevent cyberbullying could use a trauma-informed framework, including inter-peer interventions to break this cycle of trauma.

Twin study of caffeine use, ADHD, and disrupted sleep in ABCD youth

Dash GF, Carter E, Karalunas SL, Hudson KA, Fair D, Feldstein Ewing SW. Twin study of caffeine use, ADHD, and disrupted sleep in ABCD youth. Health Psychol. 2022 Nov 28. doi: 10.1037/hea0001252. Epub ahead of print. PMID: 36442048.

Objective: Evidence suggests that caffeine use disproportionately impacts sleep functioning among youth with attention-deficit/hyperactivity disorder (ADHD). The present study aimed to examine the association of caffeine use with disrupted sleep, and to test moderating effects of ADHD, by leveraging differences within twin pairs to explore potential quasi-causal (i.e., within-pair) effects.

Method: N = 765 complete same-sex twin pairs (mean age at baseline = 10.14 [SD = .5]; 49% girls; 73% white) from the ABCD study reported caffeine use and frequency of disrupted sleep; parents reported youth ADHD symptoms. Cotwin control analyses predicted disrupted sleep from caffeine use, ADHD, and their interaction at ages 10 and 12.

Results: Neither quasi-causal within-pair effects of caffeine use on disrupted sleep, nor a moderating role of ADHD were identified. Posthoc biometric models indicated that genetic and environmental influences on these phenotypes may change over time, such that genetic influences on disrupted sleep began to emerge more robustly around early adolescence. Additionally, caffeine use and disrupted sleep, but not ADHD, displayed overlapping genetic influences (12-13% of total phenotypic variance) at age 10.

Conclusions: In a sample of preadolescent twin pairs from the ABCD Study, we did not observe evidence that caffeine use was quasi-causally associated with disrupted sleep at this early developmental stage. However, caffeine use and disrupted sleep emerged with shared etiologic influences. In sum, this study sets the stage for examining these dynamic patterns in future examinations of this critical and timely ABCD study sample, as genetic and environmental influences on behavior are known to change throughout development. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Maternal age at birth and child attention-deficit hyperactivity disorder: causal association or familial confounding?

Baker BH, Joo YY, Park J, Cha J, Baccarelli AA, Posner J. Maternal age at birth and child attention-deficit hyperactivity disorder: causal association or familial confounding? J Child Psychol Psychiatry. 2022 Nov 28. doi: 10.1111/jcpp.13726. Epub ahead of print. PMID: 36440655.

Background: Causal explanations for the association of young motherhood with increased risk for child attention-deficit hyperactivity disorder (ADHD) remain unclear.

Methods: The ABCD Study recruited 11,878 youth from 22 sites across the United States between June 1, 2016 and October 15, 2018. This cross-sectional analysis of 8,514 children aged 8-11 years excluded 2,260 twins/triplets, 265 adopted children, and 839 younger siblings. We examined associations of maternal age with ADHD clinical range diagnoses based on the Child Behavior Checklist and NIH Toolbox Flanker Attention Scores using mixed logistic and linear regression models, respectively. We conducted confounding and causal mediation analyses using genotype array, demographic, socioeconomic, and prenatal environment data to investigate which genetic and environmental variables may explain the association between young maternal age and child ADHD.

Results: In crude models, each 10-year increase in maternal age was associated with 32% decreased odds of ADHD clinical range diagnosis (OR = 0.68; 95% CI [0.59, 0.78]) and 1.09-points increased NIH Flanker Attention Scores (β = 1.09; 95% CI [0.76, 1.41]), indicating better child visual selective attention. However, adjustment for confounders weakened these associations. The strongest confounders were family income, caregiver education, and ADHD polygenic risk score for ADHD clinical range diagnoses, and family income, caregiver education, and race/ethnicity for NIH Flanker Attention Scores. Breastfeeding duration, prenatal alcohol exposure, and prenatal tobacco exposure were responsible for up to 18%, 6%, and 4% mediation, respectively.

Conclusions: Socioeconomic disadvantages were likely the primary explanation for the association of young maternal age with child ADHD, although genetics and modifiable environmental factors also played a role. Public policies aimed at reducing the burden of ADHD associated with young motherhood should target socioeconomic inequalities and support young pregnant women by advocating for reduced prenatal tobacco exposure and healthy breastfeeding practices after childbirth.

Continuity versus change in latent profiles of emotion regulation and working memory during adolescence

Huffman LG & Oshri A. Continuity versus change in latent profiles of emotion regulation and working memory during adolescence. Developmental Cognitive Neuroscience, Volume 58, December 2022, 101177. https://doi.org/10.1016/j.dcn.2022.101177

Significant structural and functional brain development occurs during early adolescence. These changes underlie developments in central neurocognitive processes such as working memory (WM) and emotion regulation (ER). The preponderance of studies modeling trajectories of adolescent brain development use variable-centered approaches, omitting attention to individual differences that may undergird neurobiological embedding of early life stress and attendant psychopathology. This preregistered, data-driven study used latent transition analysis (LTA) to identify (1) latent profiles of neural function during a WM and implicit ER task, (2) transitions in profiles across 24 months, and 3) associations between transitions, parental support, and subsequent psychopathology. Using two waves of data from the ABCD Study (Mage T1 = 10; Mage T2 = 12), we found three unique profiles of neural function at both T1 and T2. The Typical, Emotion Hypo-response, and Emotion-Hyper response profiles were characterized by, respectively: moderate amygdala activation and fusiform deactivation; high ACC, fusiform, and insula deactivation; and high amygdala, ACC, and insula response to ER. While 69.5 % remained in the Typical profile from T1 to T2, 27.8 % of the sample moved from one profile at T1 to another at T2. However, neither latent profiles nor transitions exhibited associations between parental support or psychopathology symptoms.

Association between Asthma and Suicidality in 9–12-Year-Old Youths

Hoffman KW, Visoki E, Argabright ST, Schultz LM, Didomenico GE, Tran KT, Gordon JH, Chaiyachati BH, Moore TM, Almasy L, Barzilay R. Association between Asthma and Suicidality in 9–12-Year-Old Youths. Brain Sci. 2022, 12(12), 1602; https://doi.org/10.3390/brainsci12121602

Purpose: Suicidal ideation and attempts in youth are a growing health concern, and more data are needed regarding their biological underpinnings. Asthma is a common chronic inflammatory disorder in youth and has been associated with suicidal ideation and attempts in adolescent and adult populations, but data in younger children and early adolescents are lacking. We wished to study associations of asthma with childhood suicidality considering asthma’s potential as a clinically relevant model for childhood chronic immune dysregulation. Methods: Using data from the Adolescent Brain Cognitive Development (ABCD) Study (n = 11,876, 47.8% female, mean age 9.9 years at baseline assessment and 12.0 years at two-year follow-up), we assessed associations between asthma and suicidal ideation and attempts through baseline to two-year follow-up. Results: Asthma history as defined by parent report (n = 2282, 19.2% of study population) was associated with suicide attempts (SA) (odds ratio (OR) = 1.44, p = 0.01), and this association remained significant even when controlling for demographics, socioeconomic factors, and environmental factors (OR = 1.46, p = 0.028). History of asthma attacks was associated with both suicidal ideation (SI) and SA when controlling for demographics, socioeconomic factors, and environmental factors (OR = 1.27, p = 0.042; OR = 1.83, p = 0.004, respectively). The association of asthma attack with SA remained significant when controlling for self-reported psychopathology (OR = 1.92, p = 0.004). The total number of asthma attacks was associated with both SI and SA (OR = 1.03, p = 0.043; OR = 1.06, p = 0.05, respectively). Conclusions: Findings suggest an association between asthma and suicidality in early adolescence. Further research is needed to investigate mechanisms underlying this relationship.

Hierarchical Modeling of Psychosocial, Parental, and Environmental Factors for Susceptibility to Tobacco Product Use in 9-10-Year-Old Children

Dai HD, Pierce J, Beseler C, Abadi A, Zoucha K, Johnson R, Buckley J, Ramos AK. Hierarchical Modeling of Psychosocial, Parental, and Environmental Factors for Susceptibility to Tobacco Product Use in 9-10-Year-Old Children. J Adolesc Health. 2022 Nov 21:S1054-139X(22)00698-X. doi: 10.1016/j.jadohealth.2022.09.021. Epub ahead of print. PMID: 36424333.

Purpose: Tobacco use during early adolescence can harm brain development and cause adverse health outcomes. Identifying susceptibility in early adolescence before initiation presents an opportunity for tobacco use prevention.

Methods: Data were drawn from the Adolescent Brain and Cognitive Development study that enrolled 9-10-year-old children in 21 US cities between 2016 and 2018 at baseline. Separate nested hierarchical models were performed to incrementally examine the associations of sociodemographic factors, psychosocial influences, parental substance use, immediate social contacts, and perceived neighborhood safety with tobacco use susceptibility among never tobacco users (n = 10,449), overall and stratified by gender.

Results: A total of 16.6% of youths who have never used tobacco reported susceptibility to tobacco. Females (vs. males, adjusted odds ratio [AOR] [95% confidence interval {CI}] = 0.80 [0.70-0.91]), positive parental monitoring (AOR [95% CI] = 0.76 [0.66-0.87]) and positive school environment (AOR [95% CI] = 0.95 [0.93-0.98]) were associated with reduced susceptibility to tobacco use. Parental education level (high school, AOR [95% CI] = 1.52 [1.02-2.28]; bachelor’s degree, AOR [95% CI] = 1.53 [1.03-2.28]; or postgraduate degree, AOR [95% CI] = 1.54 [1.03-2.3] vs. less than high school), youth substance ever use (AOR [95% CI] = 2.24 [1.95-2.58]), internalizing problems (AOR [95% CI] = 1.03 [1-1.06]), and high scores on negative urgency, lack of premeditation, lack of perseverance, sensation seeking, and positive urgency-impulsive behavior scale were associated with increased susceptibility to tobacco use. Stratified analysis showed that parent-perceived neighborhood safety was associated with reduced susceptibility to tobacco use among males but not among females (AOR [95% CI] = 0.89 [0.81-0.99]) vs. (AOR [95% CI] = 1.01 [0.9-1.13]). A positive school environment was associated with lower susceptibility to tobacco use among females but not among males.

Discussion: Parental, environmental, and psychosocial factors influence early childhood tobacco susceptibility. Family and school-based tobacco prevention programs should consider integrating these factors into primary school curricula to reduce youth tobacco susceptibility and later initiation.

Adverse childhood experiences and binge-eating disorder in early adolescents

Chu J, Raney JH, Ganson KT, Wu K, Rupanagunta A, Testa A, Jackson DB, Murray SB, Nagata JM. Adverse childhood experiences and binge-eating disorder in early adolescents. J Eat Disord. 2022 Nov 16;10(1):168. doi: 10.1186/s40337-022-00682-y. PMID: 36384578.

Background: Adverse childhood experiences (ACEs) are common and linked to negative health outcomes. Previous studies have found associations between ACEs and binge-eating disorder (BED), though they have mainly focused on adults and use cross-sectional data. The objective of this study was to examine the associations between ACEs and BED in a large, national cohort of 9-14-year-old early adolescents in the US.

Methods: We analyzed prospective cohort data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 10,145, 2016-2020). Logistic regression analyses were used to determine the associations between self-reported ACEs and BED based on the Kiddie Schedule for Affective Disorders and Schizophrenia at two-year follow-up, adjusting for sex, race/ethnicity, baseline household income, parental education, site, and baseline binge-eating disorder.

Results: In the sample, (49% female, 46% racial/ethnic minority), 82.8% of adolescents reported at least one ACE and 1.2% had a diagnosis of BED at two-year follow-up. The mean number of ACEs was higher in those with a diagnosis of BED compared to those without (2.6 ± 0.14 vs 1.7 ± 0.02). The association between number of ACEs and BED in general had a dose-response relationship. One ACE (adjusted odds ratio [aOR] 3.48, 95% confidence interval [CI] 1.11-10.89), two ACEs (aOR 3.88, 95% CI 1.28-11.74), and three or more ACEs (aOR 8.94, 95% CI 3.01-26.54) were all associated with higher odds of BED at two-year follow-up. When stratified by types of ACEs, history of household mental illness (aOR 2.18, 95% 1.31-3.63), household violence (aOR 2.43, 95% CI 1.42-4.15), and criminal household member (aOR 2.14, 95% CI 1.23-3.73) were most associated with BED at two-year follow-up.

Conclusions: Children and adolescents who have experienced ACEs, particularly household challenges, have higher odds of developing BED. Clinicians may consider screening for ACEs and providing trauma-focused care when evaluating patients for BED.

Five recommendations for using large-scale publicly available data to advance health among American Indian peoples: the Adolescent Brain and Cognitive Development (ABCD) StudySM as an illustrative case

White, E.J., Demuth, M.J., Wiglesworth, A. et al. Five recommendations for using large-scale publicly available data to advance health among American Indian peoples: the Adolescent Brain and Cognitive Development (ABCD) StudySM as an illustrative case. Neuropsychopharmacol. (2022). https://doi.org/10.1038/s41386-022-01498-9

American Indian and Alaska Native (AIAN) populations have suffered a history of exploitation and abuse within the context of mental health research and related fields. This history is rooted in assimilation policies, historical trauma, and cultural loss, and is promulgated through discrimination and disregard for traditional culture and community knowledge. In recognition of this history, it is imperative for researchers to utilize culturally sensitive approaches that consider the context of tribal communities to better address mental health issues for AIAN individuals. The public availability of data from large-scale studies creates both opportunities and challenges when studying mental health within AIAN populations. This manuscript has two goals; first, showcase an example of problematic use of Adolescent Brain Cognitive Development (ABCD) StudySM data to promulgate stereotypes about AIAN individuals and, second, in partnership with collaborators from Cherokee Nation, we provide five recommendations for utilizing data from publicly available datasets to advance health research in AIAN populations. Specifically, we argue for the consideration of (1) the heterogeneity of the communities represented, (2) the importance of focusing on AIAN health and well-being, (3) engagement of relevant communities and AIAN community leaders, (4) consideration of historical and ongoing injustices, and (5) engagement with AIAN regulatory agencies or review boards. These recommendations are founded on principles from broader indigenous research efforts emphasizing community-engaged research and principles of Indigenous Data Sovereignty and Governance.

COVID-19-related financial strain and adolescent mental health

Argabright ST, Tran KT, Visoki E, DiDomenico GE, Moore TM, Barzilay R. COVID-19-related financial strain and adolescent mental health. The Lancet, Online first, 100391, Nov. 15, 2022. DOI:https://doi.org/10.1016/j.lana.2022.100391

Background
The COVID-19 pandemic and associated responses have induced a host of crises worldwide, including an economic recession and a global mental health crisis. The specific effects of recession on youth mental health are understudied. We aimed to examine the mechanisms by which pandemic-related financial strain may affect mental health in a diverse sample of American adolescents.

Methods
We analyzed data from the Adolescent Brain Cognitive Development Study (ABCD Study®), a large, longitudinal study of diverse US adolescents which collected data before and during the pandemic (N = 9,720, mean age 12.9 years, 18.2% Black). Linear mixed-effects models tested associations of financial strain (parent-reported household wage loss and youth-reported financial stress) with depressive symptomatology over time, covarying for multiple confounders including pre-pandemic socioeconomic status and psychopathology, and pandemic-related environmental factors. Longitudinal mediation analyses examined potential mechanisms leading from wage loss to youth mental health.

Findings
Financial strain was highly prevalent, especially among low-income participants, with >70% of the total sample reporting lost wages. Both wage loss and subjective financial stress were associated with depressive symptomatology over time (Estimate = 0.04, P = 0.014; Estimate = 0.17, P < 0.001; respectively). The association between financial stress and depressive symptomatology was robust to the addition of multiple environmental confounders (Estimate = 0.16, P < 0.001). Both family-level (family conflict) and individual-level (financial stress) factors mediated the relationship between wage loss and depressive symptomatology.

Interpretation
The financial effects of COVID-19 (and worldwide responses to it) have taken a significant toll on youth mental health. In families that lost wages, youth-reported financial stress and familial factors mediated the relationship between wage loss and mental health over time. Findings highlight financial stress as a key driver of youth mental health burden and identify familial factors as critical targets for intervention to mitigate mental health risks in periods of economic crises.

Longitudinal impact of COVID-19 pandemic on mental health of children in the ABCD study cohort

Hamatani, S., Hiraoka, D., Makita, K. et al. Longitudinal impact of COVID-19 pandemic on mental health of children in the ABCD study cohort. Sci Rep 12, 19601 (2022). https://doi.org/10.1038/s41598-022-22694-z

A large longitudinal study on the impact of the COVID-19 pandemic on mental health in children is limited. This large-scale longitudinal observational study examines the pandemic’s effects on children’s mental health while considering the effects of parental care styles. The Adolescent Brain Cognitive Development Study is a large-scale, longitudinal multicenter study in the United States. Of the 11,875 children aged 9–12 years in its database, 4702 subjects were selected for this study. The child behavior checklist and parental monitoring questionnaire (PMQ) were used to assess children’s mental health and parental support styles, respectively. Data collected before and during the pandemic were compared. Withdrawn/depressed and attention problems significantly worsened during compared to before the COVID-19 pandemic (p < 0.001, withdrawn/depressed; 53.4 ± 5.7 to 53.7 ± 5.9, attention problems; 53.4 ± 5.4 to 53.6 ± 5.6). However, the T scores are in the normal range both before and during the crisis. Simple slope analysis found withdrawn/depressed problems and aggressive behavior worsened when the PMQ was 1 SD below the mean, and rule-breaking behavior was improved when the PMQ was 1 SD above the mean. While the COVID-19 pandemic exacerbated children’s depressive symptoms and attention issues, the effects may be minor. Additionally, parental involvement serve as a protective factor for the child’s mental health even during the pandemic.

Cortical profiles of numerous psychiatric disorders and normal development share a common pattern

Cao Z, Cupertino RB, Ottino-Gonzalez J, Murphy A, Pancholi D, Juliano A, Chaarani B, Albaugh M, Yuan D, Schwab N, Stafford J, Goudriaan AE, Hutchison K, Li CR, Luijten M, Groefsema M, Momenan R, Schmaal L, Sinha R, van Holst RJ, Veltman DJ, Wiers RW, Porjesz B, Lett T, Banaschewski T, Bokde ALW, Desrivières S, Flor H, Grigis A, Gowland P, Heinz A, Brühl R, Martinot JL, Martinot MP, Artiges E, Nees F, Orfanos DP, Paus T, Poustka L, Hohmann S, Millenet S, Fröhner JH, Robinson L, Smolka MN, Walter H, Winterer J, Schumann G, Whelan R, Bhatt RR, Zhu A, Conrod P, Jahanshad N, Thompson PM, Mackey S, Garavan H; IMAGEN Consortium; ENIGMA Addiction Working Group. Cortical profiles of numerous psychiatric disorders and normal development share a common pattern. Mol Psychiatry. 2022 Nov 15. doi: 10.1038/s41380-022-01855-6. Epub ahead of print. PMID: 36380235.

The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany atlas derived from three large-scale datasets comprising a total of 41,075 neurotypical participants. PCA produced a spatially broad first principal component (PC1) that was reproducible across datasets. Then PC1 derived from healthy adult participants was compared to the pattern of CT differences associated with psychiatric and neurological disorders comprising a total of 14,886 cases and 20,962 controls from seven ENIGMA disease-related working groups, normative maturation and aging comprising a total of 17,697 scans from the ABCD Study® and the IMAGEN developmental study, and 17,075 participants from the ENIGMA Lifespan working group, as well as gene expression maps from the Allen Human Brain Atlas. Results revealed substantial spatial correspondences between PC1 and widespread lower CT observed in numerous psychiatric disorders. Moreover, the PC1 pattern was also correlated with the spatial pattern of normative maturation and aging. The transcriptional analysis identified a set of genes including KCNA2, KCNS1 and KCNS2 with expression patterns closely related to the spatial pattern of PC1. The gene category enrichment analysis indicated that the transcriptional correlations of PC1 were enriched to multiple gene ontology categories and were specifically over-represented starting at late childhood, coinciding with the onset of significant cortical maturation and emergence of psychopathology during the prepubertal-to-pubertal transition. Collectively, the present study reports a reproducible latent pattern of CT that captures interregional profiles of cortical changes in both normative brain maturation and a spectrum of psychiatric disorders. The pubertal timing of the expression of PC1-related genes implicates disrupted neurodevelopment in the pathogenesis of the spectrum of psychiatric diseases emerging during adolescence.

Genetic and Environmental Variation in Continuous Phenotypes in the ABCD Study®

Maes HHM, Lapato DM, Schmitt JE, Luciana M, Banich MT, Bjork JM, Hewitt JK, Madden PA, Heath AC, Barch DM, Thompson WK, Iacono WG, Neale MC. Genetic and Environmental Variation in Continuous Phenotypes in the ABCD Study®. Behav Genet. 2022 Nov 10. doi: 10.1007/s10519-022-10123-w. Epub ahead of print. PMID: 36357558.

Twin studies yield valuable insights into the sources of variation, covariation and causation in human traits. The ABCD Study® (abcdstudy.org) was designed to take advantage of four universities known for their twin research, neuroimaging, population-based sampling, and expertise in genetic epidemiology so that representative twin studies could be performed. In this paper we use the twin data to: (i) provide initial estimates of heritability for the wide range of phenotypes assessed in the ABCD Study using a consistent direct variance estimation approach, assuring that both data and methodology are sound; and (ii) provide an online resource for researchers that can serve as a reference point for future behavior genetic studies of this publicly available dataset. Data were analyzed from 772 pairs of twins aged 9-10 years at study inception, with zygosity determined using genotypic data, recruited and assessed at four twin hub sites. The online tool provides twin correlations and both standardized and unstandardized estimates of additive genetic, and environmental variation for 14,500 continuously distributed phenotypic features, including: structural and functional neuroimaging, neurocognition, personality, psychopathology, substance use propensity, physical, and environmental trait variables. The estimates were obtained using an unconstrained variance approach, so they can be incorporated directly into meta-analyses without upwardly biasing aggregate estimates. The results indicated broad consistency with prior literature where available and provided novel estimates for phenotypes without prior twin studies or those assessed at different ages. Effects of site, self-identified race/ethnicity, age and sex were statistically controlled. Results from genetic modeling of all 53,172 continuous variables, including 38,672 functional MRI variables, will be accessible via the user-friendly open-access web interface we have established, and will be updated as new data are released from the ABCD Study. This paper provides an overview of the initial results from the twin study embedded within the ABCD Study, an introduction to the primary research domains in the ABCD study and twin methodology, and an evaluation of the initial findings with a focus on data quality and suitability for future behavior genetic studies using the ABCD dataset. The broad introductory material is provided in recognition of the multidisciplinary appeal of the ABCD Study. While this paper focuses on univariate analyses, we emphasize the opportunities for multivariate, developmental and causal analyses, as well as those evaluating heterogeneity by key moderators such as sex, demographic factors and genetic background.

Attention deficit hyperactivity disorder symptoms and brain morphology: examining confounding bias

Dall’Aglio L, Kim HH, Lamballais S, Labrecque J, Muetzel RL, Tiemeier H. Attention deficit hyperactivity disorder symptoms and brain morphology: examining confounding bias. Elife. 2022 Nov 9;11:e78002. doi: 10.7554/eLife.78002. Epub ahead of print. PMID: 36350121.

Background: Associations between attention-deficit/hyperactivity disorder (ADHD) and brain morphology have been reported, although with several inconsistencies. These may partly stem from confounding bias, which could distort associations and limit generalizability. We examined how associations between brain morphology and ADHD symptoms change with adjustments for potential confounders typically overlooked in the literature (aim 1), and for IQ and head motion, which are typically corrected for but play ambiguous roles (aim 2).

Methods: Participants were 10-year-old children from the Adolescent Brain Cognitive Development (N=7,722) and Generation R (N=2,531) studies. Cortical area, volume, and thickness were measured with MRI and ADHD symptoms with the Child Behavior Checklist. Surface-based cross-sectional analyses were run.

Results: ADHD symptoms related to widespread cortical regions when solely adjusting for demographic factors. Additional adjustments for socioeconomic and maternal behavioral confounders (aim 1) generally attenuated associations, as cluster sizes halved and effect sizes substantially reduced. Cluster sizes further changed when including IQ and head motion (aim 2), however, we argue that adjustments might have introduced bias.

Conclusions: Careful confounder selection and control can help identify more robust and specific regions of associations for ADHD symptoms, across two cohorts. We provided guidance to minimizing confounding bias in psychiatric neuroimaging.

Psychotic-Like Experiences Associated with Sleep Disturbance and Brain Volumes in Youth: Findings from the Adolescent Brain Cognitive Development Study

Lunsford-Avery JR, Damme KSF, Vargas T, Sweitzer MM, Mittal VA. Psychotic-Like Experiences Associated with Sleep Disturbance and Brain Volumes in Youth: Findings from the Adolescent Brain Cognitive Development Study. JCPP Adv. 2021 Dec;1(4):e12055. doi: 10.1002/jcv2.12055. Epub 2021 Dec 2. PMID: 36339462; PMCID: PMC9635573.

Background: Sleep disturbance is characteristic of schizophrenia and at-risk populations, suggesting a possible etiological role in psychosis. Biological mechanisms underlying associations between sleep and psychosis vulnerability are unclear, although reduced sleep-regulatory brain structure volumes are a proposed contributor. This study is the first to examine relationships between psychotic-like experiences (PLEs; subclinical symptoms reflecting psychosis vulnerability/risk), sleep, and brain volumes in youth.

Methods: Brain volumes of five sleep-related structures were examined in relation to PLEs and difficulties initiating and maintaining sleep (DIMS) in 9260 9-11 year-olds participating in the Adolescent Brain Cognitive Development (ABCD) study. Analytic models examined relationships between DIMS, PLEs, and brain volumes, as well as DIMS as a mediator of brain volume-PLEs relationships. Although sleep regulation structures (i.e., thalamus, basal forebrain, hypothalamus) were of primary interest, other potentially-relevant structures to sleep-related functioning and psychosis (i.e., hippocampus, amygdala) were also examined.

Results: PLEs were associated with increased DIMS as well as reduced volume in some, but not all, brain structures, including the thalamus and basal forebrain in children. DIMS was also associated with reduced left thalamus volume in youth. Increased DIMS partially, statistically mediated the relationship between left thalamic volume and PLEs, although the effect was relatively small.

Conclusions: Results highlight left thalamic volume as a potential neural mechanism underlying sleep disturbances and PLEs in childhood. Future studies should assess causal relationships between sleep, PLEs, and brain structure across adolescent development, interactions with other psychosis risk factors, and the role of sleep interventions in prevention of psychosis and a range of psychiatric conditions across the lifespan.

Addressing Social Determinants of Mental Health in Pediatrics during the COVID-19 Pandemic

Spencer AE, Sikov J, Adams WG, Jellinek M, Murphy JM, Garg A. Addressing Social Determinants of Mental Health in Pediatrics during the COVID-19 Pandemic. Acad Pediatr. 2022 Nov 6:S1876-2859(22)00560-5. doi: 10.1016/j.acap.2022.11.001. Epub ahead of print. PMID: 36351513; PMCID: PMC9637283.

In our article published in June 2019, “The Relationship Between Social Risks and the Mental Health of School-Age Children in Primary Care,” we examined the association between social risks and mental health among children screened in primary care pediatrics at an urban safety-net hospital.1 More social risks on the WE CARE screener (including caregiver education, childcare employment, food security, heat, and housing) were associated with worse overall child mental health measured with the Pediatric Symptom Checklist (PSC-17). Individually, food insecurity and unemployment were associated with worse child mental health after adjusting for sociodemographic characteristics and other social risks.

Since our paper’s publication, the COVID-19 pandemic worsened social risks and health disparities, increasing calls to improve health equity and address adverse social determinants of health (SDOH) as part of healthcare practice.2 The pandemic also accelerated an already troubling downward trend in child mental health, paired with a deepening access crisis to pediatric psychiatric services, aggravated by adverse SDOH and racism.3
In this report, we discuss our study’s findings in context of new events and research since June 2019 with particular attention to the impacts of both the pandemic and racism on SDOH, child mental health, and primary care-based screening efforts.

Prenatal Caffeine Exposure Is Linked to Elevated Sugar Intake and BMI, Altered Reward Sensitivity, and Aberrant Insular Thickness in Adolescents: An ABCD Investigation

Agarwal K, Manza P, Tejeda HA, Courville AB, Volkow ND, Joseph PV. Prenatal Caffeine Exposure Is Linked to Elevated Sugar Intake and BMI, Altered Reward Sensitivity, and Aberrant Insular Thickness in Adolescents: An ABCD Investigation. Nutrients. 2022 Nov 3;14(21):4643. doi: 10.3390/nu14214643. PMID: 36364905.

Prenatal caffeine exposure (PCE) has been positively associated with elevated body mass index (BMI) in children. Why this association occurs is unclear, but it is possible that PCE alters the in utero development of brain structures associated with food preference, leading to more total sugar intake (TSI, grams) later in childhood. To test this hypothesis, we investigated if PCE (daily/weekly/&lt;weekly vs. no exposure) and elevated BMI are associated with increased TSI, neural activation during large reward anticipation (monetary incentive delay task-functional MRI) and structural changes (thickness, mm) in taste processing regions of children (n = 5534; 9-11 years) from the large-scale Adolescent Brain Cognitive Development (ABCD) study. Linear mixed-effect models, after covariate adjustments, identified a positive association (p &lt; 0.05, all |βs| &gt; 0.01) of excessive PCE (vs. no exposure) with elevated BMI (daily/weekly/daily limit; consistent in boys and girls), increased TSI (daily) and insular thickness (daily/weekly), as well as low middle frontal cortex (MFC) activation (daily). Our sub-analysis revealed an association of daily/weekly PCE (vs. no exposure) with increased gram sugar intake from soft drinks. We also identified a positive relationship of excessive PCE with elevated TSI and increased insular thickness (a key gustatory region), while in a Sobel test, reward sensitivity (reduced brain reactivity to reward anticipation in MFC; tracks reward outcomes) mediated (Test statistic = 2.23; p = 0.02) the PCE-linked BMI changes in adolescents. Our findings suggest that excessive PCE might be detrimental to frontal lobe development and altered reward sensitivity to food, thereby increasing risk for elevated TSI and obesity. Our results support recommendations to limit caffeine intake during pregnancy.

Lower gestational age is associated with lower cortical volume and cognitive and educational performance in adolescence

Ma Q, Wang H, Rolls ET, Xiang S, Li J, Li Y, Zhou Q, Cheng W, Li F. Lower gestational age is associated with lower cortical volume and cognitive and educational performance in adolescence. BMC Med. 2022 Nov 3;20(1):424. doi: 10.1186/s12916-022-02627-3. PMID: 36329481.

Background: Gestational age (GA) is associated with later cognition and behavior. However, it is unclear how specific cognitive domains and brain structural development varies with the stepwise change of gestational duration.

Methods: This large-scale longitudinal cohort study analyzed 11,878 early adolescents’ brain volume maps at 9-10 years (baseline) and 5685 at 11-12 years (a 2-year follow-up) from the Adolescent Brain Cognitive Development (ABCD) study. According to gestational age, adolescents were divided into five categorical groups: ≤ 33 weeks, 34-35 weeks, 36 weeks, 37-39 weeks, and ≥ 40 weeks. The NIH Toolbox was used to estimate neurocognitive performance, including crystallized and fluid intelligence, which was measured for 11,878 adolescents at baseline with crystallized intelligence and relevant subscales obtained at 2-year follow-up (with participant numbers ranging from 6185 to 6310 depending on the cognitive domain). An additional large population-based cohort of 618,070 middle adolescents at ninth-grade (15-16 years) from the Danish national register was utilized to validate the association between gestational age and academic achievements. A linear mixed model was used to examine the group differences between gestational age and neurocognitive performance, school achievements, and grey matter volume. A mediation analysis was performed to examine whether brain structural volumes mediated the association between GA and neurocognition, followed with a longitudinal analysis to track the changes.

Results: Significant group differences were found in all neurocognitive scores, school achievements, and twenty-five cortical regional volumes (P < 0.05, Bonferroni corrected). Specifically, lower gestational ages were associated with graded lower cognition and school achievements and with smaller brain volumes of the fronto-parieto-temporal, fusiform, cingulate, insula, postcentral, hippocampal, thalamic, and pallidal regions. These lower brain volumes mediated the association between gestational age and cognitive function (P = 1 × 10-8, β = 0.017, 95% CI: 0.007-0.028). Longitudinal analysis showed that compared to full term adolescents, preterm adolescents still had smaller brain volumes and crystallized intelligence scores at 11-12 years.

Conclusions: These results emphasize the relationships between gestational age at birth and adolescents’ lower brain volume, and lower cognitive and educational performance, measured many years later when 9-10 and 11-12 years old. The study indicates the importance of early screening and close follow-up for neurocognitive and behavioral development for children and adolescents born with gestational ages that are even a little lower than full term.

Digital media use and sleep of adolescents: the effect of rules at home

de Poot S, Harskamp-van Ginkel MW, Vrijkotte TGM. Digitale-mediagebruik en slaap bij jongeren [Digital media use and sleep of adolescents: the effect of rules at home]. Ned Tijdschr Geneeskd. 2022 Nov 2;166:D6618. Dutch. PMID: 36633019. [Article in Dutch]

Objective: To test whether parental rules regarding the amount of digital media use is associated with the sleep of Dutch adolescents, and whether this is indirectly due to lower digital media use.

Design: Cross-sectional study METHOD: Adolescents and their parents of the Amsterdam Born Children and their Development (ABCD) study completed questionnaires in 2019 at the age of 15-16 years (n=1369; 56% girls). Parents and adolescents reported whether there are rules regarding the amount of digital media use. The adolescents also reported their daily amount of digital media use, sleep duration, bedtime and sleep quality according to the Pittsburgh Sleep Quality Index (PSQI). We tested the association between rules and sleep duration, bedtime and sleep quality in adolescents using multivariate regression analysis. Using mediation analysis we tested whether rules were also indirectly associated with sleep outcome measures through the amount of digital media use.

Results: Setting rules regarding digital media use was related to sleep duration; 6.8 minutes (95%CI:0.1;13.5) longer with inconsistently experienced rules and 18.5 minutes (95%CI:9.2;27.8) longer with consistently existing rules. Setting rules was also related to bedtime; 10 minutes (95%CI: -17;-4) earlier with inconsistently experienced rules and 29 minutes (95%CI:-38;-2) earlier with consistently existing rules. Setting rules was not directly associated with sleep quality. Indirectly, rules were associated with longer sleep duration, earlier bedtime and better sleep quality due to lower digital media use per day.

Conclusion: Parental rules regarding the amount of digital media use is associated with better sleep of adolescents. This is partly explained by lower digital media use.

Socioeconomic resources are associated with distributed alterations of the brain’s intrinsic functional architecture in youth

Sripada C, Gard AM, Angstadt M, Taxali A, Greathouse T, McCurry K, Hyde LW, Weigard A, Walczyk P, Heitzeg M. Socioeconomic resources are associated with distributed alterations of the brain’s intrinsic functional architecture in youth. Developmental Cognitive Neuroscience, Volume 58, 2022, 101164, ISSN 1878-9293, https://doi.org/10.1016/j.dcn.2022.101164.

Abstract: Little is known about how exposure to limited socioeconomic resources (SER) in childhood gets “under the skin” to shape brain development, especially using rigorous whole-brain multivariate methods in large, adequately powered samples. The present study examined resting state functional connectivity patterns from 5821 youth in the Adolescent Brain Cognitive Development (ABCD) study, employing multivariate methods across three levels: whole-brain, network-wise, and connection-wise. Across all three levels, SER was associated with widespread alterations across the connectome. However, critically, we found that parental education was the primary driver of neural associations with SER. These parental education associations with the developing connectome exhibited notable concentrations in somatosensory and subcortical regions, and they were partially accounted for by home enrichment activities, child’s cognitive abilities, and child’s grades, indicating interwoven links between parental education, child stimulation, and child cognitive performance. These results add a new data-driven, multivariate perspective on links between household SER and the child’s developing functional connectome.

Poverty, Cortical Structure, and Psychopathologic Characteristics in Adolescence

Kim HH, McLaughlin KA, Chibnik LB, Koenen KC, Tiemeier H. Poverty, Cortical Structure, and Psychopathologic Characteristics in Adolescence. JAMA Netw Open. 2022 Nov 1;5(11):e2244049. doi: 10.1001/jamanetworkopen.2022.44049. PMID: 36445708.

Importance: Childhood poverty has been associated with increased internalizing and externalizing problems in adolescence, a period of peak onset for psychiatric problems. The underlying neural mechanisms remain unclear because longitudinal studies of poverty, brain structure, and changes in psychiatric symptoms are lacking.

Objective: To examine whether structural differences in cortical regions mediate the association between household poverty and change in psychiatric symptoms in early adolescence.

Design, setting, and participants: This longitudinal cohort study used baseline and 1-year follow-up data from the Adolescent Brain Cognitive Development Study. Children aged 9 to 10 years in the US were enrolled between September 1, 2016, and October 15, 2018. Data analysis was performed from August 13, 2021, to September 30, 2022.

Exposures: Household poverty as measured by income-to-needs ratio, which incorporates family income and adjusts for family size as a percentage of the federal poverty level.

Main outcomes and measures: Mediators were children’s cortical surface area, thickness, and volume, obtained using magnetic resonance imaging. Internalizing and externalizing problems at 1-year follow-up were outcomes measured by maternal report using the Child Behavior Checklist. Analyses were adjusted for baseline psychiatric problems and sociodemographic variables, including sex, race and ethnicity, parental educational level, and study site.

Results: Of the 7569 children (mean [SD] age, 9.91 [0.62] years; 3970 boys [52.5%]) included in the analysis, 1042 children (13.8%) lived below the poverty threshold between 2016 and 2018. Poverty was associated with increased externalizing symptoms score at 1-year follow-up (b = 1.57; 95% CI, 1.14-1.99), even after adjustment for baseline externalizing symptoms (b = 0.35; 95% CI, 0.06-0.64). The longitudinal associations of poverty with increases in externalizing problems over time were mediated by reductions in surface area in multiple cortical regions that support executive functioning (middle frontal gyrus), decision-making (lateral orbitofrontal cortex), visual processing (fusiform gyrus), auditory processing (transverse temporal gyrus), and emotion and language processing (superior temporal gyrus).

Conclusions and relevance: The findings of this study suggest that childhood poverty is associated with increases in externalizing problems, but not internalizing problems, over time in early adolescence. This association is mediated by reductions in cortical surface area across numerous brain regions. These findings highlight potential neurobiological mechanisms underlying the link between poverty and the emergence of externalizing problems during early adolescence.

Reward sensitivity and internalizing symptoms during the transition to puberty: An examination of 9-and 10-year-olds in the ABCD Study

McNeilly EA, Saragosa-Harris NM, Mills KL, Dahl RE, Magis-Weinberg L. Reward sensitivity and internalizing symptoms during the transition to puberty: An examination of 9-and 10-year-olds in the ABCD Study. Dev Cogn Neurosci. 2022 Oct 31;58:101172. doi: 10.1016/j.dcn.2022.101172. Epub ahead of print. PMID: 36368089.

Early pubertal timing has been linked to increased risk for internalizing psychopathology in adolescents. Work in older adolescents and adults suggests that heightened reward sensitivity may buffer risk for internalizing symptoms. However, few studies have investigated these associations during the early transition to puberty, a window of vulnerability to mental health risk. In this preregistered study, we investigated the associations among pubertal timing, internalizing symptoms, and reward sensitivity in a large, population-based sample of 11,224 9-10 year-olds from the ABCD Study®. Using split-half analysis, we tested for within-sample replications of hypothesized effects across two age- and sex-matched subsets of the sample. Early pubertal timing was associated with higher internalizing symptoms in female and male participants across samples, with 9-10 year-olds in the mid-pubertal stage at the highest risk for internalizing symptoms. Additionally, early pubertal timing was robustly associated with greater self-reported reward sensitivity in both female and male participants. We observed inconsistent evidence for a moderating role of reward sensitivity across measurement domains (self-report, behavioral, and fMRI data), several of which differed by sex, but none of these interactions replicated across samples. Together, these findings provide unique insights into early indicators of risk for internalizing psychopathology during the transition to puberty in a large, population-based, demographically diverse sample of youth.

Bayesian multisource data integration for explainable brain-behavior analysis

Chen R. Bayesian multisource data integration for explainable brain-behavior analysis. Front Neurosci. 2022 Oct 28;16:1044680. doi: 10.3389/fnins.2022.1044680. PMID: 36389240; PMCID: PMC9650064.

Different data sources can provide complementary information. Moving from a simple approach based on using one data source at a time to a systems approach that integrates multiple data sources provides an opportunity to understand complex brain disorders or cognitive processes. We propose a data fusion method, called Bayesian Multisource Data Integration, to model the interactions among data sources and behavioral variables. The proposed method generates representations from data sources and uses Bayesian network modeling to associate representations with behavioral variables. The generated Bayesian network is transparent and easy to understand. Bayesian inference is used to understand how the perturbation of representation is related to behavioral changes. The proposed method was assessed on the simulated data and data from the Adolescent Brain Cognitive Development study. For the Adolescent Brain Cognitive Development study, we found diffusion tensor imaging and resting-state functional magnetic resonance imaging were synergistic in understanding the fluid intelligence composite and the total score composite in healthy youth (9-11 years of age).

Caregiver monitoring, but not caregiver warmth, is associated with general cognition in two large sub-samples of youth

Keller AS, Mackey AP, Pines A, Fair D, Feczko E, Hoffman MS, Salum GA, Barzilay R, Satterthwaite TD. Caregiver monitoring, but not caregiver warmth, is associated with general cognition in two large sub-samples of youth. Dev Sci. 2022 Oct 28:e13337. doi: 10.1111/desc.13337. Epub ahead of print. PMID: 36305770.

Individual differences in cognitive abilities emerge early during development, and children with poorer cognition are at increased risk for adverse outcomes as they enter adolescence. Caregiving plays an important role in supporting cognitive development, yet it remains unclear how specific types of caregiving behaviors may shape cognition, highlighting the need for large-scale studies. In the present study, we characterized replicable yet specific associations between caregiving behaviors and cognition in two large sub-samples of children ages 9-10 years old from the Adolescent Brain Cognitive Development Study® (ABCD). Across both discovery and replication sub-samples, we found that child reports of caregiver monitoring (supervision or regular knowledge of the child’s whereabouts) were positively associated with general cognition abilities, after covarying for age, sex, household income, neighborhood deprivation, and parental education. This association was specific to the type of caregiving behavior (caregiver monitoring, but not caregiver warmth), and was most strongly associated with a broad domain of general cognition (but not executive function or learning/memory). Additionally, we found that caregiver monitoring partially mediated the association between household income and cognition, furthering our understanding of how socioeconomic disparities may contribute to disadvantages in cognitive development. Together, these findings underscore the influence of differences in caregiving behavior in shaping youth cognition.

Sex differences in regional gray matter density in pre-adolescent binge eating disorder: a voxel-based morphometry study

Murray SB, Diaz-Fong JP, Duval CJ, Balkchyan AA, Nagata JM, Lee DJ, Ganson KT, Toga AW, Siegel SJ, Jann K. Sex differences in regional gray matter density in pre-adolescent binge eating disorder: a voxel-based morphometry study. Psychol Med. 2022 Oct 28:1-13. doi: 10.1017/S0033291722003269. Epub ahead of print. PMID: 36305572.

Background: Binge eating disorder (BED) is a pernicious psychiatric disorder which is linked with broad medical and psychiatric morbidity, and obesity. While BED may be characterized by altered cortical morphometry, no evidence to date examined possible sex-differences in regional gray matter characteristics among those with BED. This is especially important to consider in children, where BED symptoms often emerge coincident with rapid gray matter maturation.

Methods: Pre-adolescent, 9-10-year old boys (N = 38) and girls (N = 33) with BED were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development Study. We investigated sex differences in gray matter density (GMD) via voxel-based morphometry. Control sex differences were also assessed in age and body mass index and developmentally matched control children (boys N = 36; girls N = 38). Among children with BED, we additionally assessed the association between dorsolateral prefrontal (dlPFC) GMD and parent-reported behavioral approach and inhibition tendencies.

Results: Girls with BED uniquely demonstrate diffuse clusters of greater GMD (p < 0.05, Threshold Free Cluster Enhancement corrected) in the (i) left dlPFC (p = 0.003), (ii) bilateral dmPFC (p = 0.004), (iii) bilateral primary motor and somatosensory cortex (p = 0.0003) and (iv) bilateral precuneus (p = 0.007). Brain-behavioral associations suggest a unique negative correlation between GMD in the left dlPFC and behavioral approach tendencies among girls with BED.

Conclusions: Early-onset BED may be characterized by regional sex differences in terms of its underlying gray matter morphometry.

State-Level Recreational Cannabis Legalization Is Not Differentially Associated with Cannabis Risk Perception Among Children: A Multilevel Regression Analysis

Gilman JM, Iyer MT, Pottinger EG, Klugman EM, Hughes D, Potter K, Tervo-Clemmens B, Roffman JL, Evins AE. State-Level Recreational Cannabis Legalization Is Not Differentially Associated with Cannabis Risk Perception Among Children: A Multilevel Regression Analysis. Cannabis Cannabinoid Res. 2022 Oct 26. doi: 10.1089/can.2022.0162. Epub ahead of print. PMID: 36301559.

Introduction: As more states pass recreational cannabis laws (RCLs) for adults, there is concern that increasing (and state-sanctioned) cannabis acceptance will result in a reduced perception of risk of harm from cannabis among children. We aimed to discover whether children in states with RCLs had decreased perception of risk from cannabis compared with children in states with illicit cannabis. Methods: We analyzed data from the multisite multistate Adolescent Brain and Cognitive Development Study to determine how the perception of cannabis harm among children (age at baseline: 9-10; N=10,395) changes over time in states with and without RCLs. Using multilevel modeling, we assessed survey responses from children longitudinally across 3 years, adjusting for state-, family-, and participant-level clustering and child-level factors, including demographics (sex, race, and socioeconomic status), religiosity, and trait impulsivity. Results: There was no significant main effect of state RCLs on perceived risk of cannabis use, and no differences in change over time by state RCLs, even after controlling for demographic factors and other risk (e.g., impulsivity) and protective (e.g., religiosity) factors. Conclusions: This analysis indicates that state-level RCLs are not associated with differential perception of cannabis risk among children, even after controlling for demographics, trait impulsivity, and religiosity. Future studies could assess how perception of risk from cannabis changes as children and adolescents continue to mature in states with and without RCLs.

A multicohort geometric deep learning study of age dependent cortical and subcortical morphologic interactions for fluid intelligence prediction

Wu Y, Besson P, Azcona EA, Bandt SK, Parrish TB, Breiter HC, Katsaggelos AK. A multicohort geometric deep learning study of age dependent cortical and subcortical morphologic interactions for fluid intelligence prediction. Sci Rep. 2022 Oct 22;12(1):17760. doi: 10.1038/s41598-022-22313-x. PMID: 36273036; PMCID: PMC9588039.

The relationship of human brain structure to cognitive function is complex, and how this relationship differs between childhood and adulthood is poorly understood. One strong hypothesis suggests the cognitive function of Fluid Intelligence (Gf) is dependent on prefrontal cortex and parietal cortex. In this work, we developed a novel graph convolutional neural networks (gCNNs) for the analysis of localized anatomic shape and prediction of Gf. Morphologic information of the cortical ribbons and subcortical structures was extracted from T1-weighted MRIs within two independent cohorts, the Adolescent Brain Cognitive Development Study (ABCD; age: 9.93 ± 0.62 years) of children and the Human Connectome Project (HCP; age: 28.81 ± 3.70 years). Prediction combining cortical and subcortical surfaces together yielded the highest accuracy of Gf for both ABCD (R = 0.314) and HCP datasets (R = 0.454), outperforming the state-of-the-art prediction of Gf from any other brain measures in the literature. Across both datasets, the morphology of the amygdala, hippocampus, and nucleus accumbens, along with temporal, parietal and cingulate cortex consistently drove the prediction of Gf, suggesting a significant reframing of the relationship between brain morphology and Gf to include systems involved with reward/aversion processing, judgment and decision-making, motivation, and emotion.

Strengthening associations between psychotic like experiences and suicidal ideation and behavior across middle childhood and early adolescence

Karcher NR, O’Hare K, Jay SY, Grattan R. Strengthening associations between psychotic like experiences and suicidal ideation and behavior across middle childhood and early adolescence. Psychol Med. 2022 Oct 21:1-9. doi: 10.1017/S0033291722003166. Epub ahead of print. PMID: 36268881.

Background: Understanding risk factors related to suicidal ideation (SI) and suicidal behaviors (SB) in youth is important for informing prevention and intervention efforts. While it appears that psychotic-like experiences (PLEs) are strongly associated with both SI and SB at different points across the lifespan, the longitudinal nature of this relationship in middle childhood and early adolescence is understudied.

Methods: The study used the unique longitudinal Adolescent Brain Cognitive Development Study data. Mixed effects linear models examined associations between PLEs and SI and SB over time using three time points of data from ages 9-13.

Results: First, analyses indicated that endorsement of SI and SB increased as youth grew older for those with increased distressing PLEs. Analyses found evidence of bidirectional relationships between PLEs with SI and SB, with evidence that PLEs at baseline were associated with worsening SI and SB over time, including a transition from SI to SB (β = 0.032, FDRp = 0.002). Exploratory analyses showed consistent evidence for strengthened associations over time for higher delusional ideation with both SI and SB (βs > 0.04, FDRps < 0.001), and for perceptual distortions with SB (βs = 0.046, FDRp < 0.001). When accounting for general psychopathology, for SB, the strengthened associations over time was significantly stronger for PLEs (β = 0.053, FDRp < 0.001) compared to general psychopathology (β = 0.022, FDRp = 0.01).

Conclusions: The present study indicates both SI and SB show strengthened associations with PLEs over time, and that baseline PLEs may predict worsening of suicidality over time. The findings are important clarifications about the nature of the associations between youth-reported PLEs and suicidality over time.

Longitudinal assessment of brain structure and behaviour in youth with rapid weight gain: Potential contributing causes and consequences

Adise S, Marshall AT, Hahn S, Zhao S, Kan E, Rhee KE, Herting MM, Sowell ER. Longitudinal assessment of brain structure and behaviour in youth with rapid weight gain: Potential contributing causes and consequences. Pediatr Obes. 2022 Oct 17:e12985. doi: 10.1111/ijpo.12985. Epub ahead of print. PMID: 36253967./

Objective: Independent of weight status, rapid weight gain has been associated with underlying brain structure variation in regions associated with food intake and impulsivity among pre-adolescents. Yet, we lack clarity on how developmental maturation coincides with rapid weight gain and weight stability.

Methods: We identified brain predictors of 2-year rapid weight gain and its longitudinal effects on brain structure and impulsivity in the Adolescent Brain Cognitive DevelopmentSM Study®. Youth were categorized as Healthy Weight/Weight Stable (WSHW , n = 527) or Weight Gainers (WG, n = 221, >38lbs); 63% of the WG group were healthy weight at 9-to-10-years-old.

Results: A fivefold cross-validated logistic elastic-net regression revealed that rapid weight gain was associated with structural variation amongst 39 brain features at 9-to-10-years-old in regions involved with executive functioning, appetitive control and reward sensitivity. Two years later, WG youth showed differences in change over time in several of these regions and performed worse on measures of impulsivity.

Conclusions: These findings suggest that brain structure in pre-adolescence may predispose some to rapid weight gain and that weight gain itself may alter maturational brain change in regions important for food intake and impulsivity. Behavioural interventions that target inhibitory control may improve trajectories of brain maturation and facilitate healthier behaviours.

Parental religiosity is associated with changes in youth functional network organization and cognitive performance in early adolescence

Brooks, S.J., Tian, L., Parks, S.M. et al. Parental religiosity is associated with changes in youth functional network organization and cognitive performance in early adolescence. Sci Rep 12, 17305 (2022). https://doi.org/10.1038/s41598-022-22299-6

Parental religious beliefs and practices (religiosity) may have profound effects on youth, especially in neurodevelopmentally complex periods such as adolescence. In n = 5566 children (median age = 120.0 months; 52.1% females; 71.2% with religious affiliation) from the Adolescent Brain Cognitive Development study, relationships between parental religiosity and non-religious beliefs on family values (data on youth beliefs were not available), topological properties of youth resting-state brain networks, and executive function, inhibitory control, and cognitive flexibility were investigated. Lower caregiver education and family income were associated with stronger parental beliefs (p < 0.01). Strength of both belief types was correlated with lower efficiency, community structure, and robustness of frontoparietal control, temporoparietal, and dorsal attention networks (p < 0.05), and lower Matrix Reasoning scores. Stronger religious beliefs were negatively associated (directly and indirectly) with multiscale properties of salience and default-mode networks, and lower Flanker and Dimensional Card Sort scores, but positively associated with properties of the precuneus. Overall, these effects were small (Cohen’s d ~ 0.2 to ~ 0.4). Overlapping neuromodulatory and cognitive effects of parental beliefs suggest that early adolescents may perceive religious beliefs partly as context-independent rules on expected behavior. However, religious beliefs may also differentially affect cognitive flexibility, attention, and inhibitory control and their neural substrates.

Association between parental age, brain structure, and behavioral and cognitive problems in children

Du, J., Rolls, E.T., Gong, W. et al. Association between parental age, brain structure, and behavioral and cognitive problems in children. Mol Psychiatry 27, 967–975 (2022). https://doi.org/10.1038/s41380-021-01325-5

Objective
To investigate the relation between parental age, and behavioral, cognitive and brain differences in the children.

Method
Data with children aged 9–11 of 8709 mothers with parental age 15–45 years were analyzed from the Adolescent Brain Cognitive Development (ABCD) study. A general linear model was used to test the associations of the parental age with brain structure, and behavioral and cognitive problems scores.

Results
Behavioral and cognitive problems were greater in the children of the younger mothers, and were associated with lower volumes of cortical regions in the children. There was a linear correlation between the behavioral and cognitive problems scores, and the lower brain volumes (r > 0.6), which was evident when parental age was included as a stratification factor. The regions with lower volume included the anterior cingulate cortex, medial and lateral orbitofrontal cortex and amygdala, parahippocampal gyrus and hippocampus, and temporal lobe (FDR corrected p < 0.01). The lower cortical volumes and areas in the children significantly mediated the association between the parental age and the behavioral and cognitive problems in the children (all p < 10−4). The effects were large, such as the 71.4% higher depressive problems score, and 27.5% higher rule-breaking score, in the children of mothers aged 15–19 than the mothers aged 34–35.

Conclusions
Lower parental age is associated with behavioral problems and reduced cognitive performance in the children, and these differences are related to lower volumes and areas of some cortical regions which mediate the effects in the children. The findings are relevant to psychiatric understanding and assessment.

Attention-Deficit/Hyperactivity Disorder: Restricted Phenotypes Prevalence, Comorbidity, and Polygenic Risk Sensitivity in the ABCD Baseline Cohort

Cordova MM, Antovich DM, Ryabinin P, Neighbor C, Mooney MA, Dieckmann NF, Miranda-Dominguez O, Nagel BJ, Fair DA, Nigg JT. Attention-Deficit/Hyperactivity Disorder: Restricted Phenotypes Prevalence, Comorbidity, and Polygenic Risk Sensitivity in the ABCD Baseline Cohort. J Am Acad Child Adolesc Psychiatry. 2022 Oct;61(10):1273-1284. doi: 10.1016/j.jaac.2022.03.030. Epub 2022 Apr 12. PMID: 35427730.

Objective: To evaluate the prevalence and major comorbidities of ADHD using different operational definitions in a newly available national dataset and to test the utility of operational definitions against genetic and cognitive correlates.

Method: The US Adolescent Brain Cognitive Development (ABCD) Study enrolled 11,878 children aged 9-10 years at baseline. ADHD prevalence, comorbidity, and association with polygenic risk score and laboratory-assessed executive functions were calculated at 4 thresholds of ADHD phenotype restrictiveness. Bias from missingness, sampling, and nesting were addressed statistically.

Results: Prevalence of current ADHD for 9- to 10-year old children was 3.53% (95% CI 3.14%-3.92%) when Computerized Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS-COMP) score and parent and teacher ratings were required to converge. Of ADHD cases so defined, 70% had a comorbid psychiatric disorder. After control for overlapping comorbidity and ruling out for psychosis or low IQ, 30.9% (95% CI 25.7%-36.7%) had a comorbid disruptive behavior disorder, 27.4% (95% CI 22.3%-33.1%) had an anxiety or fear disorder, and 2.1% (95% CI 1.2%-3.8%) had a mood disorder. Children in the top decile of polygenic load incurred a 63% increased chance of having ADHD vs the bottom half of polygenic load (p < .01)-an effect detected only with a stringent phenotype definition. Dimensional latent variables for irritability, externalizing, and ADHD yielded convergent results for cognitive correlates.

Conclusion: This fresh estimate of national prevalence of ADHD in the United States suggests that the DSM-5 definition requiring multiple informants yields a prevalence of about 3.5%. Results may inform further ADHD studies in the ABCD sample.

Impact of prenatal cannabis exposure on functional connectivity of the salience network in children

Faraj MM, Evanski J, Zundel CG, Peters C, Brummelte S, Lundahl L, Marusak HA. Impact of prenatal cannabis exposure on functional connectivity of the salience network in children. J Neurosci Res. 2022 Oct 13. doi: 10.1002/jnr.25136. Epub ahead of print. PMID: 36226844.

Cannabis use among pregnant people has increased over the past decade. This is of concern as prenatal cannabis exposure (PCE) is associated with cognitive, motor, and social deficits among offspring. Here, we examined resting-state functional connectivity (rsFC) of the salience network (SN)-a core neurocognitive network that integrates emotional and sensory information-in children with (vs. without) PCE. Using neuroimaging and developmental history data collected from 10,719 children (M ± SD = 9.92 ± 0.62 years; 47.9% female) from the Adolescent Brain Cognitive Development study, we assessed the impact of parent-reported PCE (before or after knowledge of pregnancy) on rsFC within and between the SN and five other core neurocognitive networks. We also evaluated whether SN rsFC mediated the association between PCE and child psychopathology. Results showed that PCE before (but not after) knowledge of pregnancy was associated with lower SN-ventral attention network (VAN) rsFC. Furthermore, psychotic-like experiences mediated the association between PCE and SN-VAN rsFC, and reversal of the model was also significant, such that SN-VAN rsFC mediated the association between PCE and psychotic-like symptoms. However, these mediation effects were no longer significant after the inclusion of covariates. Taken together, these findings suggest that developmental alterations in SN-VAN interactions may explain the previously reported association between PCE and elevated risk of child psychopathology.

Family History of Depression and Neural Reward Sensitivity: Findings from the ABCD Study

Freeman C, Olino T, Barbeau EB, Weinberg A, Chai X (In Press, 2022). Family History of Depression and Neural Reward Sensitivity: Findings from the ABCD Study. Biological Psychiatry, Archival Report. Published:October 12, 2022, DOI:https://doi.org/10.1016/j.bpsc.2022.09.015.

Background
Previous studies have found that offspring of depressed parents exhibit reduced striatal reward response to anticipating and receiving rewards, suggesting this may constitute a neurobiological risk marker for depression. The present study aimed to assess whether maternal and paternal depression history have independent effects on offspring reward processing and whether greater family history density of depression is associated with increased blunting of striatal reward responses.

Methods
Data from the baseline visit of the Adolescent Brain Cognitive Development Study were used. After exclusion criteria, 7233 9- and 10-year-old children (49% female) were included in analyses. Neural responses to reward anticipation and receipt in the Monetary Incentive Delay Task were examined in six striatal regions of interest. Using mixed-effect models, we evaluated the effect of maternal or paternal depression history on striatal reward response. We also evaluated the effect of family history density on reward response.

Results
Across all six striatal ROIs, neither maternal nor paternal depression significantly predicted blunted response to reward anticipation or feedback. Contrary to hypotheses, paternal depression history was associated with increased response in the left caudate during anticipation and maternal depression history was associated with increased response in the left putamen during feedback. Family history density was not associated with striatal reward response.

Conclusion
Our findings suggest that family history of depression is not strongly associated with blunted striatal reward response in 9- and 10-year-old children. Factors contributing to heterogeneity across studies need to be examined in future research to reconcile these results with past findings.

Task-based co-activation patterns reliably predict resting state canonical network engagement during development

Ye F, Kohler R, Serio B, Lichenstein S, Yip SW. Task-based co-activation patterns reliably predict resting state canonical network engagement during development. Dev Cogn Neurosci. 2022 Oct 8;58:101160. doi: 10.1016/j.dcn.2022.101160. Epub ahead of print. PMID: 36270101; PMCID: PMC9583448.

Neurodevelopmental research has traditionally focused on development of individual structures, yet multiple lines of evidence indicate parallel development of large-scale systems, including canonical neural networks (i.e., default mode, frontoparietal). However, the relationship between region- vs. network-level development remains poorly understood. The current study tests the ability of a recently developed multi-task coactivation matrix approach to predict canonical resting state network engagement at baseline and at two-year follow-up in a large and cohort of young adolescents. Pre-processed tabulated neuroimaging data were obtained from the Adolescent Brain and Cognitive Development (ABCD) study, assessing youth at baseline (N = 6073, age = 10.0 ± 0.6 years, 3056 female) and at two-year follow-up (N = 3539, age = 11.9 ± 0.6 years, 1726 female). Individual multi-task co-activation matrices were constructed from the beta weights of task contrasts from the stop signal task, the monetary incentive delay task, and emotional N-back task. Activation-based predictive modeling, a cross-validated machine learning approach, was adopted to predict resting-state canonical network engagement from multi-task co-activation matrices at baseline. Note that the tabulated data used different parcellations of the task fMRI data (“ASEG” and Desikan) and the resting-state fMRI data (Gordon). Despite this, the model successfully predicted connectivity within the default mode network (DMN, rho = 0.179 ± 0.002, p < 0.001) across participants and identified a subset of co-activations within parietal and occipital macroscale brain regions as key contributors to model performance, suggesting an underlying common brain functional architecture across cognitive domains. Notably, predictive features for resting-state connectivity within the DMN identified at baseline also predicted DMN connectivity at two-year follow-up (rho = 0.258). These results indicate that multi-task co-activation matrices are functionally meaningful and can be used to predict resting-state connectivity. Interestingly, given that predictive features within the co-activation matrices identified at baseline can be extended to predictions at a future time point, our results suggest that task-based neural features and models are valid predictors of resting state network level connectivity across the course of development. Future work is encouraged to verify these findings with more consistent parcellations between task-based and resting-state fMRI, and with longer developmental trajectories.

Association of Video Gaming With Cognitive Performance Among Children

Chaarani B, Ortigara J, Yuan D, Loso H, Potter A, Garavan HP. Association of Video Gaming With Cognitive Performance Among Children. JAMA Netw Open. 2022 Oct 3;5(10):e2235721. doi: 10.1001/jamanetworkopen.2022.35721. PMID: 36279138.

Importance: Although most research has linked video gaming to subsequent increases in aggressive behavior in children after accounting for prior aggression, findings have been divided with respect to video gaming’s association with cognitive skills.

Objective: To examine the association between video gaming and cognition in children using data from the Adolescent Brain Cognitive Development (ABCD) study.

Design, setting, and participants: In this case-control study, cognitive performance and blood oxygen level-dependent (BOLD) signal were compared in video gamers (VGs) and non-video gamers (NVGs) during response inhibition and working memory using task-based functional magnetic resonance imaging (fMRI) in a large data set of 9- and 10-year-old children from the ABCD study, with good control of demographic, behavioral, and psychiatric confounding effects. A sample from the baseline assessment of the ABCD 2.0.1 release in 2019 was largely recruited across 21 sites in the US through public, private, and charter elementary schools using a population neuroscience approach to recruitment, aiming to mirror demographic variation in the US population. Children with valid neuroimaging and behavioral data were included. Some exclusions included common MRI contraindications, history of major neurologic disorders, and history of traumatic brain injury.

Exposures: Participants completed a self-reported screen time survey including an item asking children to report the time specifically spent on video gaming. All fMRI tasks were performed by all participants.

Main outcomes and measures: Video gaming time, cognitive performance, and BOLD signal assessed with n-back and stop signal tasks on fMRI. Collected data were analyzed between October 2019 and October 2020.

Results: A total of 2217 children (mean [SD] age, 9.91 [0.62] years; 1399 [63.1%] female) participated in this study. The final sample used in the stop signal task analyses consisted of 1128 NVGs (0 gaming hours per week) and 679 VGs who played at least 21 hours per week. The final sample used in the n-back analyses consisted of 1278 NVGs who had never played video games (0 hours per week of gaming) and 800 VGs who played at least 21 hours per week. The VGs performed better on both fMRI tasks compared with the NVGs. Nonparametric analyses of fMRI data demonstrated a greater BOLD signal in VGs in the precuneus during inhibitory control. During working memory, a smaller BOLD signal was observed in VGs in parts of the occipital cortex and calcarine sulcus and a larger BOLD signal in the cingulate, middle, and frontal gyri and the precuneus.

Conclusions and relevance: In this study, compared with NVGs, VGs were found to exhibit better cognitive performance involving response inhibition and working memory as well as altered BOLD signal in key regions of the cortex responsible for visual, attention, and memory processing. The findings are consistent with videogaming improving cognitive abilities that involve response inhibition and working memory and altering their underlying cortical pathways.

Effects of sleep duration on neurocognitive development in early adolescents in the USA: a propensity score matched, longitudinal, observational study

Yang FN, Xie W, Wang Z. Effects of sleep duration on neurocognitive development in early adolescents in the USA: a propensity score matched, longitudinal, observational study. The Lancet Child & Adolescent Health (2022), Volume 6, Issue 10, October 2022, Pages 705-712, DOI:https://doi.org/10.1016/S2352-4642(22)00188-2.

Background
Although the American Academy of Sleep Medicine suggests at least 9 h of sleep per day for 6–12-year-olds, children in recent generations often report sleeping less than this amount. Because early adolescence is a crucial period for neurocognitive development, we aimed to investigate how insufficient sleep affects children’s mental health, cognition, brain function, and brain structure over 2 years.

Methods
In this propensity score matched, longitudinal, observational cohort study, we obtained data from a population-based sample of 9–10-year-olds from 21 US study sites in the ongoing Adolescent Brain Cognitive Development (ABCD) study. Participants were categorised as having sufficient sleep or insufficient sleep on the basis of a cutoff of 9 h sleep per day. Using propensity score matching, we matched these two groups of participants on 11 key covariates, including sex, socioeconomic status, and puberty status. Participants were excluded from our analysis if they did not pass a baseline resting-state functional MRI quality check or had missing data for the covariates involved in propensity score matching. Outcome measures retrieved from the ABCD study were behavioural problems, mental health, cognition, and structural and resting-state functional brain measures, assessed at baseline and at 2-year follow-up. We examined group differences on these outcomes over those 2 years among all eligible participants. We then did mediation analyses of the neural correlates of behavioural changes induced by insufficient sleep.

Findings

Between Sept 1, 2016, and Oct 15, 2018, 11 878 individuals had baseline data collected for the ABCD study, of whom 8323 were eligible and included in this study (4142 participants in the sufficient sleep group and 4181 in the insufficient sleep group). Follow-up data were collected from July 30, 2018, to Jan 15, 2020. We identified 3021 matched sufficient sleep–insufficient sleep pairs at baseline and 749 matched pairs at 2-year follow-up, and observed similar differences between the groups in behaviour and neural measures at both timepoints; the effect sizes of between-group differences in behavioural measures at these two timepoints were significantly correlated with each other (r=0·85, 95% CI 0·73–0·92; p<0·0001). A similar pattern was observed in resting-state functional connectivity (r=0·54, 0·45–0·61; p<0·0001) and in structural measures (eg, in grey matter volume r=0·61, 0·51–0·69; p<0·0001). We found that cortico–basal ganglia functional connections mediate the effects of insufficient sleep on depression, thought problems, and crystallised intelligence, and that structural properties of the anterior temporal lobe mediate the effect of insufficient sleep on crystallised intelligence.

Interpretation

These results provide population-level evidence for the long-lasting effect of insufficient sleep on neurocognitive development in early adolescence. These findings highlight the value of early sleep intervention to improve early adolescents’ long-term developmental outcomes.

Multiple Instance Neuroimage Transformer

Singla A, Zhao Q, Do DK, Zhou Y, Pohl KM, Adeli E. Multiple Instance Neuroimage Transformer. Predict Intell Med. 2022 Sep;13564:36-48. doi: 10.1007/978-3-031-16919-9_4. Epub 2022 Sep 16. PMID: 36331280; PMCID: PMC9629332.

For the first time, we propose using a multiple instance learning based convolution-free transformer model, called Multiple Instance Neuroimage Transformer (MINiT), for the classification of T1-weighted (T1w) MRIs. We first present several variants of transformer models adopted for neuroimages. These models extract non-overlapping 3D blocks from the input volume and perform multi-headed self-attention on a sequence of their linear projections. MINiT, on the other hand, treats each of the non-overlapping 3D blocks of the input MRI as its own instance, splitting it further into non-overlapping 3D patches, on which multi-headed self-attention is computed. As a proof-of-concept, we evaluate the efficacy of our model by training it to identify sex from T1w-MRIs of two public datasets: Adolescent Brain Cognitive Development (ABCD) and the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA). The learned attention maps highlight voxels contributing to identifying sex differences in brain morphometry. The code is available at https://github.com/singlaayush/MINIT.

COVID-19 Pandemic Stress and COMT VAL158MET on Youth Externalizing Behaviours: A Longitudinal Study from the Adolescent Brain Cognitive Development (ABCD) European Subsample

Kant T, Koyama E, Zai C, Beitchman J, Kennedy JL. COVID-19 PANDEMIC STRESS AND COMT VAL158MET ON YOUTH EXTERNALIZING BEHAVIOURS: A LONGITUDINAL STUDY FROM THE ADOLESCENT BRAIN COGNITIVE DEVELOPMENT (ABCD) EUROPEAN SUBSAMPLE. Eur Neuropsychopharmacol. 2022 Oct;63:e152–3. doi: 10.1016/j.euroneuro.2022.07.280. Epub 2022 Sep 23. PMCID: PMC9502142.

Background: Youth externalizing problems is one of the leading risk factors for violence and death in youth. The interaction between genetics and increased stress has been associated with an increased risk for externalizing behaviors. COVID-19 pandemic is a major current environmental stressor, with increasing both inter and intra violence and aggression. Previous studies demonstrating an influence of catechol-o-methyltransferase (COMT) Val158Met on youth externalizing behaviors suggest that youth with higher genetic risk may be more susceptible to exhibiting increased externalizing behaviors due to the pandemic stress. This study examines the possible influence of Val158Met and stress from the pandemic on youth externalizing behaviors in a longitudinal sample.

Methods: Participants were 4098 children (2185M:1913F) of European ancestry, confirmed genetically using ancestry PCA, and recruited longitudinally as part of the Adolescent Brain Cognitive Development (ABCD) study. Val158Met(rs4680) genotypes were obtained from the Smokescreen® Genotyping Array.

Externalizing Problems were analyzed using the externalizing behavior scores from Child Behavior Checklist collected before COVID (until 2020 February) and during COVID (after March 2020). Stress scores were analyzed using the collected questionnaires from the families during the pandemic. Data analyses were performed using PLINK and R. Linear fixed effects model – repeated measures were used, with collection time, genotype, and COVID-19 stress scores as fixed factors, and site ID and subject ID as random factors.

Results: The interaction between genotype and collection time was significant (p=0.017): Val carriers scored higher on externalizing behaviors at both time points, however, Met/Met carriers showed a significant increase in their scores during the pandemic while Val carriers scored similarly in both times. When COVID-19 stress scores were entered into the model, the gene x collection time interaction was marginally significant (p=0.071), with youth with higher stress scores reporting higher externalizing behaviors regardless of their genotype.

Discussion: To our knowledge, this is the first study to demonstrate the effects of the stress from the COVID-19 pandemic with Val158Met genotype on youth externalizing behaviors during the pandemic. Results propose that youth with Met/Met genotype are more susceptible to exhibiting increased externalizing behaviors during the pandemic. This emphasizes the importance of studying the effects of COVID-19 on children’s behaviors with increased genetic risk and may serve as a base for developing novel personalized prevention and treatment techniques for youth.

White matter microstructure shows sex differences in late childhood: Evidence from 6797 children

Lawrence KE, Abaryan Z, Laltoo E, Hernandez LM, Gandal MJ, McCracken JT, Thompson PM. White matter microstructure shows sex differences in late childhood: Evidence from 6797 children. Hum Brain Mapp. 2022 Sep 29. doi: 10.1002/hbm.26079. Epub ahead of print. PMID: 36177528.

Sex differences in white matter microstructure have been robustly demonstrated in the adult brain using both conventional and advanced diffusion-weighted magnetic resonance imaging approaches. However, sex differences in white matter microstructure prior to adulthood remain poorly understood; previous developmental work focused on conventional microstructure metrics and yielded mixed results. Here, we rigorously characterized sex differences in white matter microstructure among over 6000 children from the Adolescent Brain Cognitive Development study who were between 9 and 10 years old. Microstructure was quantified using both the conventional model-diffusion tensor imaging (DTI)-and an advanced model, restriction spectrum imaging (RSI). DTI metrics included fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). RSI metrics included normalized isotropic, directional, and total intracellular diffusion (N0, ND, NT). We found significant and replicable sex differences in DTI or RSI microstructure metrics in every white matter region examined across the brain. Sex differences in FA were regionally specific. Across white matter regions, boys exhibited greater MD, AD, and RD than girls, on average. Girls displayed increased N0, ND, and NT compared to boys, on average, suggesting greater cell and neurite density in girls. Together, these robust and replicable findings provide an important foundation for understanding sex differences in health and disease.

Effects of Parental Internalizing and Externalizing Behavior Problems on Children’s Limbic Brain Structures—An MRI Study

Albar Z & Sattar A. Effects of Parental Internalizing and Externalizing Behavior Problems on Children’s Limbic Brain Structures—An MRI Study. Brain Sci. Sept. 29, 2022, 12(10), 1319; https://doi.org/10.3390/brainsci12101319

Parental behavior problems have long-term effects on children’s limbic brain structures and functions. Parental behavior problems-related brain changes in children may lead to mental disorders and behavior dysfunction later in life. However, our understanding of the relationship between parental behavior and children’s brain structures is less obvious when children and adolescents are studied in a general population without mental disorders. The majority of studies on the relationship between parental behavior and adolescent brain structure have been focused on severe forms of the following parental behavior problems: (1) internalizing behavior associated with mood and anxiety disorders, and (2) externalizing behavior associated with substance use and violence. A few studies examined the effect of normative variations or subtle differences in parental behavior. Therefore, we utilized a large study—Adolescent Brain Cognitive Development (ABCD)—to determine relationships between normative variation in parental internalizing and externalizing behavior and limbic brain structures in children and adolescents without mental disorders. Quantile (median) regression models were used to compute associations between parental behavior and children’s limbic structures. We found that parental internalizing and externalizing behaviors are uniquely associated with children’s limbic structures after adjustment for biological confounders and parental socioeconomic status. Our findings indicate that normative parental behavior may have a significant early influence on limbic structures of normally developing children and adolescents. Accelerated or delayed limbic structure maturation may account for children’s and adolescents’ behavioral inadequacies and a risk of developing specific mood disorders or substance abuse problems later in life.

Exploring the Relationships Between Autozygosity, Educational Attainment, and Cognitive Ability in a Contemporary, Trans-Ancestral American Sample

Colbert SM, Keller MC, Agrawal A, Johnson EC. Exploring the Relationships Between Autozygosity, Educational Attainment, and Cognitive Ability in a Contemporary, Trans-Ancestral American Sample. Behav Genet. 2022 Sep 28. doi: 10.1007/s10519-022-10113-y. Epub ahead of print. PMID: 36169746.

Previous studies have found significant associations between estimated autozygosity – the proportion of an individual’s genome contained in homozygous segments due to distant inbreeding – and multiple traits, including educational attainment (EA) and cognitive ability. In one study, estimated autozygosity showed a stronger association with parental EA than the subject’s own EA. This was likely driven by parental EA’s association with mobility: more educated parents tended to migrate further from their hometown, and because of the strong correlation between ancestry and geography in the Netherlands, these individuals chose partners farther from their ancestry and therefore more different from them genetically. We examined the associations between estimated autozygosity, cognitive ability, and parental EA in a contemporary sub-sample of adolescents from the Adolescent Brain Cognitive Development Study℠ (ABCD Study®) (analytic N = 6,504). We found a negative association between autozygosity and child cognitive ability consistent with previous studies, while the associations between autozygosity and parental EA were in the expected direction of effect (with greater levels of autozygosity being associated with lower EA) but the effect sizes were significantly weaker than those estimated in previous work. We also found a lower mean level of autozygosity in the ABCD sample compared to previous autozygosity studies, which may reflect overall decreasing levels of autozygosity over generations. Variation in spousal similarities in ancestral background in the ABCD study compared to other studies may explain the pattern of associations between estimated autozygosity, EA, and cognitive ability in the current study.

Concordance in child-parent reporting of social victimization experiences in the Adolescent Brain Cognitive Development (ABCD) study

Tang JT, Saadi A, Dunn EC, Choi K. Concordance in child-parent reporting of social victimization experiences in the Adolescent Brain Cognitive Development (ABCD) study. Acad Pediatr. 2022 Sep 28:S1876-2859(22)00503-4. doi: 10.1016/j.acap.2022.09.018. Epub ahead of print. PMID: 36182088.

Objective: To investigate child-parent concordance in reporting social victimization experiences and whether concordance was associated with child behavioral symptoms.

Methods: This was an observational study with data from the Adolescent Brain Cognitive Development (ABCD) study. The analytic sample was 11235 9- or 10-year-old children from the United States. Exposure variables were demographic and protective factors (child perceptions of parental relationships, school protective factors, neighborhood safety). The outcome was parent-child concordance on six domains of child social victimization: conventional crime, peer victimization, witnessing violence, internet victimization, school victimization, and gun violence. Child behavior symptoms were measured using the Child Behavior Checklist.

Results: Exposure to social victimization was low (9% of the sample). Concordance ranged from 18-50%. The highest levels of concordance were observed for conventional crime (k=0.48, P<.001) and witnessing violence (k=0.48, P<.001). Parents’ perceptions of greater neighborhood safety was associated with lower odds of concordant conventional crime (OR= 0.92, 95% CI=0.86-0.99) and witnessing violence (OR=0.92, 95% CI-0.84-0.99). Concordance was associated with more internalizing/externalizing behaviors.

Conclusions: Parents under-report social victimization in relation to children. Concordance in reporting social victimization may be an indicator of the severity of experiences, underscoring the need to consider child reports when screening for adversity.

Peer victimization (bullying) on mental health, behavioral problems, cognition, and academic performance in preadolescent children in the ABCD Study

Menken MS, Isaiah A, Liang H, Rivera PR, Cloak CC, Reeves G, Lever NA, Chang L. Peer victimization (bullying) on mental health, behavioral problems, cognition, and academic performance in preadolescent children in the ABCD Study. Front Psychol. 2022 Sep 26;13:925727. doi: 10.3389/fpsyg.2022.925727. PMID: 36225678; PMCID: PMC9549775.

Objective: Peer victimization is a substantial early life stressor linked to psychiatric symptoms and poor academic performance. However, the sex-specific cognitive or behavioral outcomes of bullying have not been well-described in preadolescent children.

Methods: Using the baseline dataset of the Adolescent Brain Cognitive Development (ABCD) Study 2.0.1 data repository (N = 11,875), we evaluated associations between parent-reported bullying victimization, suicidality (suicidal ideation, intent, and/or behavior), and non-suicidal self-injury (NSSI), as well as internalizing and externalizing behavioral problems, cognition, and academic performance.

Results: Of the 11,015 9-10-year-old children included in the analyses (5,263 girls), 15.3% experienced bullying victimization, as reported by the primary caregiver. Of these, boys were more likely to be bullied than girls (odds ratio [OR], 1.2 [95% CI, 1.1-1.3]; p = 0.004). Children who were bullied were more likely to display NSSI or passive suicidality (OR, 2.4 [95% CI, 2.0-2.9]; p < 0.001) and active suicidality (OR, 3.4 [95% CI, 2.7-4.2]; p < 0.001). Bullied children also had lower cognitive scores, greater behavioral problems, and poorer grades (p < 0.001). Across all participants, boys had poorer grades and greater behavioral problems than girls; however, bullied boys had greater behavioral problems than girls in several areas (p < 0.001). Compared to their non-bullied peers, bullied children with greater non-suicidal self-injury or suicidality also had greater behavioral problems and poorer grades (p < 0.001).

Conclusion: These findings highlight the sex-specific effects of bullying, and the negative associations of bullying victimization with cognitive performance, behavioral problems, and academic performance. Future longitudinal studies will identify the natural history and neural correlates of these deficits during adolescence.

Working memory and reaction time variability mediate the relationship between polygenic risk and ADHD traits in a general population sample

Moses M, Tiego J, Demontis D, Bragi Walters G, Stefansson H, Stefansson K, Børglum AD, Arnatkeviciute A, Bellgrove MA. Working memory and reaction time variability mediate the relationship between polygenic risk and ADHD traits in a general population sample. Mol Psychiatry. 2022 Sep 23. doi: 10.1038/s41380-022-01775-5. Epub ahead of print. PMID: 36151456.

Endophenotypes are heritable and quantifiable traits indexing genetic liability for a disorder. Here, we examined three potential endophenotypes, working memory function, response inhibition, and reaction time variability, for attention-deficit hyperactivity disorder (ADHD) measured as a dimensional latent trait in a large general population sample derived from the Adolescent Brain Cognitive DevelopmentSM Study. The genetic risk for ADHD was estimated using polygenic risk scores (PRS) whereas ADHD traits were quantified as a dimensional continuum using Bartlett factor score estimates, derived from Attention Problems items from the Child Behaviour Checklist and Effortful Control items from the Early Adolescent Temperament Questionnaire-Revised. The three candidate cognitive endophenotypes were quantified using task-based performance measures. Higher ADHD PRSs were associated with higher ADHD traits, as well as poorer working memory performance and increased reaction time variability. Lower working memory performance, poorer response inhibition, and increased reaction time variability were associated with more pronounced ADHD traits. Working memory and reaction time variability partially statistically mediated the relationship between ADHD PRS and ADHD traits, explaining 14% and 16% of the association, respectively. The mediation effect was specific to the genetic risk for ADHD and did not generalise to genetic risk for four other major psychiatric disorders. Together, these findings provide robust evidence from a large general population sample that working memory and reaction time variability can be considered endophenotypes for ADHD that mediate the relationship between ADHD PRS and ADHD traits.

Developmental Milestones of Infancy and Associations with Later Childhood Neurodevelopmental Outcomes in the Adolescent Brain Cognitive Development (ABCD) Study

Zhuo H, Xiao J, Tseng W-L, Liew Z. Developmental Milestones of Infancy and Associations with Later Childhood Neurodevelopmental Outcomes in the Adolescent Brain Cognitive Development (ABCD) Study. Children, Sept. 20, 2022, 9(10), 1424; https://doi.org/10.3390/children9101424

The age at attaining infancy developmental milestones has been associated with later neurodevelopmental outcomes, but evidence from large and diverse samples is lacking. We investigated this by analyzing data of 5360 singleton children aged 9–10 from 17 states in the US enrolled in the Adolescent Brain Cognitive Development (ABCD) study during 2016–2020. Delays in four milestones (first roll over, unaided sitting, unaided walking, and speaking first words) were defined using the 90th percentile of age at attainment reported by children’s biological mothers. Childhood neurocognitive function was measured by research assistants using the NIH toolbox, and children reported their behavioral problems using the Brief Problem Monitor. Linear mixed-effects models were employed to investigate the association between delays in single or multiple milestones and childhood neurobehavioral outcomes. Delays in first roll over, unaided sitting, or walking were associated with poorer childhood neurocognitive function, while delay in speaking first words was associated with both poorer neurocognitive function and behavioral problems. Children who had delays in both motor and language milestones had the worst neurocognitive function and behavioral outcomes. Our results suggest that delays in motor and language milestone attainment during infancy are predictive of childhood neurobehavioral outcomes.

Association between mild traumatic brain injury, brain structure, and mental health outcomes in the Adolescent Brain Cognitive Development Study

Lopez DA, Christensen ZP, Foxe JJ, Ziemer LR, Nicklas PR, Freedman EG. Association between mild traumatic brain injury, brain structure, and mental health outcomes in the Adolescent Brain Cognitive Development Study. NeuroImage. Volume 263, November 2022, 119626. https://doi.org/10.1016/j.neuroimage.2022.119626

Background
Children that experience a mild traumatic brain injury (mTBI) are at an increased risk of neural alterations that can deteriorate mental health. We test the hypothesis that mTBI is associated with psychopathology and that structural brain metrics (e.g., volume, area) meaningfully mediate the relation in an adolescent population.

Methods
We analyzed behavioral and brain MRI data from 11,876 children who participated in the Adolescent Brain Cognitive Development (ABCD) Study. Mixed-effects models were used to examine the longitudinal association between mTBI and mental health outcomes. Bayesian methods were used to investigate brain regions that are intermediate between mTBI and symptoms of poor mental health.

Results
There were 199 children with mTBI and 527 with possible mTBI across the three ABCD Study visits. There was a 7% (IRR = 1.07, 95% CI: 1.01, 1.13) and 15% (IRR = 1.16, 95% CI: 1.05, 1.26) increased risk of emotional or behavioral problems in children that experienced possible mTBI or mTBI, respectively. Possible mTBI was associated with a 17% (IRR: 1.17, 95% CI: 0.99, 1.40) increased risk of experiencing distress following a psychotic-like experience. We did not find any brain regions that meaningfully mediated the relationship between mTBI and mental health outcomes. Analysis of volumetric measures found that approximately 2% to 5% of the total effect of mTBI on mental health outcomes operated through total cortical volume. Image intensity measure analyses determined that approximately 2% to 5% of the total effect was mediated through the left-hemisphere of the dorsolateral prefrontal cortex.

Conclusion
Results indicate an increased risk of emotional and behavioral problems in children that experienced possible mTBI or mTBI. Mediation analyses did not elucidate the mechanisms underlying the association between mTBI and mental health outcomes.

Explaining the Association Between Fetal Growth and Childhood ADHD Symptoms: Cross-cohort Replication

Dooley N, Healy C, Brannigan R, Cotter D, Clarke M, Cannon M. Explaining the Association Between Fetal Growth and Childhood ADHD Symptoms: Cross-cohort Replication. Res Child Adolesc Psychopathol. 2022 Sep 17. doi: 10.1007/s10802-022-00971-9. Epub ahead of print. PMID: 36114937.

The association between restricted fetal growth and symptoms of attention deficit/hyperactivity disorder (ADHD) in childhood is well-replicated and robust. However, fetal growth is determined by many prenatal factors and associations with mental health may be confounded by familial and social context. In this study, we sought to quantify the relative contributions of prenatal factors and familial confounds to the association between fetal growth and ADHD symptoms. Two independent cohorts were analyzed, the Adolescent Brain Cognitive Development study (ABCD; United States) and the Growing Up in Ireland (GUI) study. ADHD symptoms were measured by the Child Behavior Checklist (ABCD) and the Strengths & Difficulties questionnaire (GUI) at age 9-10. Using sequential regression models, we assessed the change-in-association between fetal growth and ADHD symptoms after controlling for sex, familial factors (socioeconomic/demographic factors & family psychiatric history) and prenatal factors (pregnancy complications & maternal substance-use during pregnancy). Converging findings from cohorts suggested that over a quarter of the association between fetal growth and ADHD symptoms is attributable to familial confounds. The degree to which the association was explained by prenatal factors differed by cohort-pregnancy complications explained a larger proportion of the effect in ABCD (7.9%) than GUI (2.7%), and maternal substance-use explained a larger proportion of the effect in GUI (22.7%) compared to ABCD (4.8%). Different explanations of the fetal growth-ADHD association across cohorts suggests cohort-specific, and potentially nationally-specific, risk factors for fetal growth and related neurodevelopmental outcomes. The evidence suggests early prevention of ADHD in Ireland should focus on minimizing maternal smoking during pregnancy. In the US, prevention and treatment of pregnancy complications are highlighted as viable targets for intervention.

Comparison of individualized behavioral predictions across anatomical, diffusion and functional connectivity MRI

Ooi LQR, Chen J, Shaoshi Z, Kong R, Tam A, Li J, Dhamala E, Zhou JH, Holmes AJ, Yeo BTT. Comparison of individualized behavioral predictions across anatomical, diffusion and functional connectivity MRI. Neuroimage. 2022 Sep 15:119636. doi: 10.1016/j.neuroimage.2022.119636. Epub ahead of print. PMID: 36116616.

A fundamental goal across the neurosciences is the characterization of relationships linking brain anatomy, functioning, and behavior. Although various MRI modalities have been developed to probe these relationships, direct comparisons of their ability to predict behavior have been lacking. Here, we compared the ability of anatomical T1, diffusion and functional MRI (fMRI) to predict behavior at an individual level. Cortical thickness, area and volume were extracted from anatomical T1 images. Diffusion Tensor Imaging (DTI) and approximate Neurite Orientation Dispersion and Density Imaging (NODDI) models were fitted to the diffusion images. The resulting metrics were projected to the Tract-Based Spatial Statistics (TBSS) skeleton. We also ran probabilistic tractography for the diffusion images, from which we extracted the stream count, average stream length, and the average of each DTI and NODDI metric across tracts connecting each pair of brain regions. Functional connectivity (FC) was extracted from both task and resting-state fMRI. Individualized prediction of a wide range of behavioral measures were performed using kernel ridge regression, linear ridge regression and elastic net regression. Consistency of the results were investigated with the Human Connectome Project (HCP) and Adolescent Brain Cognitive Development (ABCD) datasets. In both datasets, FC-based models gave the best prediction performance, regardless of regression model or behavioral measure. This was especially true for the cognitive component. Furthermore, all modalities were able to predict cognition better than other behavioral components. Combining all modalities improved prediction of cognition, but not other behavioral components. Finally, across all behaviors, combining resting and task FC yielded prediction performance similar to combining all modalities. Overall, our study suggests that in the case of healthy children and young adults, behaviorally-relevant information in T1 and diffusion features might reflect a subset of the variance captured by FC.

Generalization of Cortical MOSTest Genome-Wide Associations Within and Across Samples

Loughnan RJ, Shadrin AA, Frei O, van der Meer D, Zhao W, Palmer CE, Thompson WK, Makowski C, Jernigan TL, Andreassen OA, Fan CC, Dale AM. Generalization of Cortical MOSTest Genome-Wide Associations Within and Across Samples. Neuroimage. 2022 Sep 14:119632. doi: 10.1016/j.neuroimage.2022.119632. Epub ahead of print. PMID: 36115590.

Genome-Wide Association studies have typically been limited to univariate analysis in which a single outcome measure is tested against millions of variants. Recent work demonstrates that a Multivariate Omnibus Statistic Test (MOSTest) is well powered to discover genomic effects distributed across multiple phenotypes. Applied to cortical brain MRI morphology measures, MOSTest has resulted in a drastic improvement in power to discover loci when compared to established approaches (min-P). One question that arises is how well these discovered loci replicate in independent data. Here we perform 10 times cross validation within 34,973 individuals from UK Biobank for imaging measures of cortical area, thickness and sulcal depth (>1,000 dimensionality for each). By deploying a replication method that aggregates discovered effects distributed across multiple phenotypes, termed PolyVertex Score (MOSTest-PVS), we demonstrate a higher replication yield and comparable replication rate of discovered loci for MOSTest (# replicated loci: 242-496, replication rate: 96-97%) in independent data when compared with the established min-P approach (# replicated loci: 26-55, replication rate: 91-93%). An out-of-sample replication of discovered loci was conducted with a sample of 4,069 individuals from the Adolescent Brain Cognitive Developmentࣨ (ABCD) study, who are on average 50 years younger than UK Biobank individuals. We observe a higher replication yield and comparable replication rate of MOSTest-PVS compared to min-P. This finding underscores the importance of using well-powered multivariate techniques for both discovery and replication of high dimensional phenotypes in Genome-Wide Association studies.

Genetic risk, parental history, and suicide attempts in a diverse sample of US adolescents

Barzilay R, Visoki E, Schultz LM, Warrier V, Daskalakis NP, Almasy L. Genetic risk, parental history, and suicide attempts in a diverse sample of US adolescents. Front Psychiatry. 2022 Sep 14;13:941772. doi: 10.3389/fpsyt.2022.941772. PMID: 36186872; PMCID: PMC9515424.

Background: Adolescent suicide is a major health problem in the US marked by a recent increase in risk of suicidal behavior among Black/African American youth. While genetic factors partly account for familial transmission of suicidal behavior, it is not clear whether polygenic risk scores of suicide attempt can contribute to suicide risk classification.

Objectives: To evaluate the contribution of a polygenic risk score for suicide attempt (PRS-SA) in explaining variance in suicide attempt by early adolescence.

Methods: We studied N = 5,214 non-related youth of African and European genetic ancestry from the Adolescent Brain Cognitive Development (ABCD) Study (ages 8.9-13.8 years) who were evaluated between 2016 and 2021. Regression models tested associations between PRS-SA and parental history of suicide attempt/death with youth-reported suicide attempt. Covariates included age and sex.

Results: Over three waves of assessments, 182 youth (3.5%) reported a past suicide attempt, with Black youth reporting significantly more suicide attempts than their White counterparts (6.1 vs. 2.8%, p < 0.001). PRS-SA was associated with suicide attempt [odds ratio (OR) = 1.3, 95% confidence interval (CI) 1.1-1.5, p = 0.001]. Parental history of suicide attempt/death was also associated with youth suicide attempt (OR = 3.1, 95% CI, 2.0-4.7, p < 0.001). PRS-SA remained significantly associated with suicide attempt even when accounting for parental history (OR = 1.29, 95% CI = 1.1-1.5, p = 0.002). In European ancestry youth (n = 4,128), inclusion of PRS-SA in models containing parental history explained more variance in suicide attempt compared to models that included only parental history (ΔR 2 = 0.7%, p = 0.009).

Conclusions: Findings suggest that PRS-SA may be useful for youth suicide risk classification in addition to established risk factors.

Evidence from “big data” for the default-mode hypothesis of ADHD: a mega-analysis of multiple large samples

Norman LJ, Sudre G, Price J, Shastri GG, Shaw P. Evidence from “big data” for the default-mode hypothesis of ADHD: a mega-analysis of multiple large samples. Neuropsychopharmacology. 2022 Sep 13. doi: 10.1038/s41386-022-01408-z. Epub ahead of print. PMID: 36100657.

We sought to identify resting-state characteristics related to attention deficit/hyperactivity disorder, both as a categorical diagnosis and as a trait feature, using large-scale samples which were processed according to a standardized pipeline. In categorical analyses, we considered 1301 subjects with diagnosed ADHD, contrasted against 1301 unaffected controls (total N = 2602; 1710 males (65.72%); mean age = 10.86 years, sd = 2.05). Cases and controls were 1:1 nearest neighbor matched on in-scanner motion and key demographic variables and drawn from multiple large cohorts. Associations between ADHD-traits and resting-state connectivity were also assessed in a large multi-cohort sample (N = 10,113). ADHD diagnosis was associated with less anticorrelation between the default mode and salience/ventral attention (B = 0.009, t = 3.45, p-FDR = 0.004, d = 0.14, 95% CI = 0.004, 0.014), somatomotor (B = 0.008, t = 3.49, p-FDR = 0.004, d = 0.14, 95% CI = 0.004, 0.013), and dorsal attention networks (B = 0.01, t = 4.28, p-FDR < 0.001, d = 0.17, 95% CI = 0.006, 0.015). These results were robust to sensitivity analyses considering comorbid internalizing problems, externalizing problems and psychostimulant medication. Similar findings were observed when examining ADHD traits, with the largest effect size observed for connectivity between the default mode network and the dorsal attention network (B = 0.0006, t = 5.57, p-FDR < 0.001, partial-r = 0.06, 95% CI = 0.0004, 0.0008). We report significant ADHD-related differences in interactions between the default mode network and task-positive networks, in line with default mode interference models of ADHD. Effect sizes (Cohen’s d and partial-r, estimated from the mega-analytic models) were small, indicating subtle group differences. The overlap between the affected brain networks in the clinical and general population samples supports the notion of brain phenotypes operating along an ADHD continuum.

Estimating Parental Demand for Children’s Screen Time in a Model of Family Labor Supply

Oh, S.E., Vukina, T. Estimating Parental Demand for Children’s Screen Time in a Model of Family Labor Supply. Int Adv Econ Res (2022). https://doi.org/10.1007/s11294-022-09854-7

In a novel approach to model the demand for the children’s screen time as the result of a parent’s optimal labor-leisure choice, the study used a simple model of parental utility maximization subject to the money and time budget constraints to derive Marshallian parental demand functions for two types of child upbringing activities: time-intensive (violin lesson) and time-saving (video games). After the Slutsky decomposition, parental demand for children’s screen time was shown to be similar to a Giffen good. Using the National Longitudinal Survey of Youth 1979 and Adolescent Brain Cognitive Development data, the wage equation was first estimated based on Heckman’s two-step correction procedure. Then, the total effect of an increase in wage rate on the parental demand for screen time was empirically decomposed into the substitution effect and the income effect. The study findings indicate that the substitution effect is positive, the income effect is negative, and the negative income effect dominates the substitution effect. We add to the existing literature by showing that the empirical findings in the public health and psychology literature can be reconciled with the theoretical predictions of the standard economic labor-leisure trade-off paradigm.

Association of Mental Health Burden With Prenatal Cannabis Exposure From Childhood to Early Adolescence: Longitudinal Findings From the Adolescent Brain Cognitive Development (ABCD) Study

Baranger DAA, Paul SE, Colbert SMC, et al. Association of Mental Health Burden With Prenatal Cannabis Exposure From Childhood to Early Adolescence: Longitudinal Findings From the Adolescent Brain Cognitive Development (ABCD) Study. JAMA Pediatr. Published online September 12, 2022. doi:10.1001/jamapediatrics.2022.3191

Dramatic increases in cannabis use during pregnancy are alarming because of evidence that prenatal exposure may be associated with a host of adverse outcomes. We previously found that prenatal cannabis exposure (PCE) following maternal knowledge of pregnancy is associated with increased psychopathology during middle childhood using baseline data from the Adolescent Brain Cognitive Development (ABCD) study. Here, leveraging longitudinal ABCD study data (data release 4.0), we examined whether associations with psychopathology persist into early adolescence.

Youth screen use in the ABCD® study

Bagot KS, Tomko RL, Marshall AT, Hermann J, Cummins K, Ksinan A, Kakalis M, Breslin F, Lisdahl KM, Mason M, Redhead JN, Squeglia LM, Thompson WK, Wade T, Tapert SF, Fuemmeler BF, Baker FC. Youth screen use in the ABCD® study. Developmental Cognitive Neuroscience, Volume 57, October 2022, 101150, https://doi.org/10.1016/j.dcn.2022.101150

Adolescent screen usage is ubiquitous and influences development and behavior. Longitudinal screen usage data coupled with psychometrically valid constructs of problematic behaviors can provide insights into these relationships. We describe methods by which the screen usage questionnaire was developed in the Adolescent Brain Cognitive Development (ABCD) Study, demonstrate longitudinal changes in screen usage via child report and describe data harmonization baseline-year 2. We further include psychometric analyses of adapted social media and video game addiction scales completed by youth. Nearly 12,000 children ages 9–10 years at baseline and their parents were included in the analyses. The social media addiction questionnaire (SMAQ) showed similar factor structure and item loadings across sex and race/ethnicities, but that item intercepts varied across both sex and race/ethnicity. The videogame addiction questionnaire (VGAQ) demonstrated the same configural, metric and scalar invariance across racial and ethnic groups, however differed across sex. Video gaming and online social activity increased over ages 9/10–11/12 (p’s < 0.001). Compared with boys, girls engaged in greater social media use (p < .001) and demonstrated higher ratings on the SMAQ (p < .001). Compared with girls, boys played more video games (p < .001) and demonstrated higher ratings on the VGAQ (p < .001). Time spent playing video games increased more steeply for boys than girls from age 9/10–11/12 years (p < .001). Black youth demonstrated significantly higher SMAQ and VGAQ scores compared to all other racial/ethnic groups. These data show the importance of considering different screen modalities beyond total screen use and point towards clear demographic differences in use patterns. With these comprehensive data, ABCD is poised to address critical questions about screen usage changes across adolescence.

Distinguish bipolar and major depressive disorder in adolescents based on multimodal neuroimaging: Results from the Adolescent Brain Cognitive Development study®

Liu Y, Chen K, Luo Y, Wu J, Xiang Q, Peng L, Zhang J, Zhao W, Li M, Zhou X. Distinguish bipolar and major depressive disorder in adolescents based on multimodal neuroimaging: Results from the Adolescent Brain Cognitive Development study®. Digit Health. 2022 Sep 5;8:20552076221123705. doi: 10.1177/20552076221123705. PMID: 36090673; PMCID: PMC9452797.

Background: Major depressive disorder and bipolar disorder in adolescents are prevalent and are associated with cognitive impairment, executive dysfunction, and increased mortality. Early intervention in the initial stages of major depressive disorder and bipolar disorder can significantly improve personal health.

Methods: We collected 309 samples from the Adolescent Brain Cognitive Development study, including 116 adolescents with bipolar disorder, 64 adolescents with major depressive disorder, and 129 healthy adolescents, and employed a support vector machine to develop classification models for identification. We developed a multimodal model, which combined functional connectivity of resting-state functional magnetic resonance imaging and four anatomical measures of structural magnetic resonance imaging (cortical thickness, area, volume, and sulcal depth). We measured the performances of both multimodal and single modality classifiers.

Results: The multimodal classifiers showed outstanding performance compared with all five single modalities, and they are 100% for major depressive disorder versus healthy controls, 100% for bipolar disorder versus healthy control, 98.5% (95% CI: 95.4-100%) for major depressive disorder versus bipolar disorder, 100% for major depressive disorder versus depressed bipolar disorder and the leave-one-site-out analysis results are 77.4%, 63.3%, 79.4%, and 81.7%, separately.

Conclusions: The study shows that multimodal classifiers show high classification performances. Moreover, cuneus may be a potential biomarker to differentiate major depressive disorder, bipolar disorder, and healthy adolescents. Overall, this study can form multimodal diagnostic prediction workflows for clinically feasible to make more precise diagnose at the early stage and potentially reduce loss of personal pain and public society.

Associations Between Genetic Risk for Adult Suicide Attempt and Suicidal Behaviors in Young Children in the US

Lee PH, Doyle AE, Silberstein M, Jung JY, Liu R, Perlis RH, Roffman J, Smoller JW, Fava M, Kessler RC. Associations Between Genetic Risk for Adult Suicide Attempt and Suicidal Behaviors in Young Children in the US. JAMA Psychiatry. 2022 Aug 31. doi: 10.1001/jamapsychiatry.2022.2379. Epub ahead of print. PMID: 36044238.

Importance: Suicide rates have been increasing among youth in the US. While the heritability of suicide risk is well established, there is limited understanding of how genetic risk is associated with suicidal thoughts and behaviors in young children.

Objective: To examine whether genetic susceptibility to suicide attempts (SAs) is associated with suicidal thoughts and behaviors in children.

Design, setting, and participants: This case-control study examined data from the Adolescent Brain Cognitive Development (ABCD) study, a population-based longitudinal study of 11 878 US children enrolled at age 9 and 10 years from September 2016 to November 2018. Youth reports of suicidal ideation (SI) and SAs were obtained from the Kiddie Schedule for Affective Disorder and Schizophrenia at baseline and 2 subsequent years. After conservative quality control of genotype data, this analysis focused on 4344 unrelated individuals of European ancestry. Data analysis was conducted from November 2020 to February 2022.

Main outcomes and measures: Children’s lifetime experiences of SI and SAs were assessed each year from ages 9 to 10 years to ages 11 to 12 years. Polygenic risk scores (PRSs) for SAs were calculated for ABCD study participants based on the largest genome-wide association study of SA cases and controls of European ancestry (total sample n = 518 612).

Results: Of 4344 children of European ancestry (2045 [47.08%] female; mean [SD] age, 9.93 [0.62] years), significant associations were found between children’s SA PRSs and their lifetime SAs with the most robust association in the follow-up year 2 (odds ratio, 1.43 [95% CI, 1.18-1.75]; corrected P = 1.85 × 10-3; Nagelkerke pseudo R2 = 1.51%). These associations remained significant after accounting for children’s sociodemographic backgrounds, psychopathology symptoms, parental histories of suicide and mental health, and PRSs for major depression and attention-deficit/hyperactivity disorder (likelihood ratio test P < .05). Children’s depressive mood and aggressive behavior were the most significant partial mediators of SA genetic risk on SAs (mediation analysis P < 1 × 10-16). Children’s behavioral problems, such as attention problems, rule-breaking behavior, and social problems, also partially mediated the association of SA PRSs with SAs (mediation analysis false discover rate < 0.05).

Conclusions and relevance: This study’s findings indicate that there may be genetic factors associated with SA risk across the life span and suggest behaviors and conditions through which the risk could be mediated in childhood. Further research is warranted to examine whether incorporating genetic data could improve the identification of children at risk for suicide.

Examining reaction time variability on the stop-signal task in the ABCD study

Epstein JN, Karalunas SL, Tamm L, Dudley JA, Lynch JD, Altaye M, Simon JO, Maloney TC, Atluri G. Examining reaction time variability on the stop-signal task in the ABCD study. J Int Neuropsychol Soc. 2022 Aug 31:1-11. doi: 10.1017/S1355617722000431. Epub ahead of print. PMID: 36043323.

Objective: Reaction time variability (RTV) has been estimated using Gaussian, ex-Gaussian, and diffusion model (DM) indices. Rarely have studies examined interrelationships among these performance indices in childhood, and the use of reaction time (RT) computational models has been slow to take hold in the developmental psychopathology literature. Here, we extend prior work in adults by examining the interrelationships among different model parameters in the ABCD sample and demonstrate how computational models of RT can clarify mechanisms of time-on-task effects and sex differences in RTs.

Method: This study utilized trial-level data from the stop signal task from 8916 children (9-10 years old) to examine Gaussian, ex-Gaussian, and DM indicators of RTV. In addition to describing RTV patterns, we examined interrelations among these indicators, temporal patterns, and sex differences.

Results: There was no one-to-one correspondence between DM and ex-Gaussian parameters. Nonetheless, drift rate was most strongly associated with standard deviation of RT and tau, while nondecisional processes were most strongly associated with RT, mu, and sigma. Performance worsened across time with changes driven primarily by decreasing drift rate. Boys were faster and less variable than girls, likely attributable to girls’ wide boundary separation.

Conclusions: Intercorrelations among model parameters are similar in children as has been observed in adults. Computational approaches play a crucial role in understanding performance changes over time and can also clarify mechanisms of group differences. For example, standard RT models may incorrectly suggest slowed processing speed in girls that is actually attributable to other factors.

Fairness-related performance and explainability effects in deep learning models for brain image analysis

Stanley EAM, Wilms M, Mouches P, Forkert ND. Fairness-related performance and explainability effects in deep learning models for brain image analysis. J Med Imaging (Bellingham). 2022 Nov;9(6):061102. doi: 10.1117/1.JMI.9.6.061102. Epub 2022 Aug 26. PMID: 36046104; PMCID: PMC9412191.

Purpose: Explainability and fairness are two key factors for the effective and ethical clinical implementation of deep learning-based machine learning models in healthcare settings. However, there has been limited work on investigating how unfair performance manifests in explainable artificial intelligence (XAI) methods, and how XAI can be used to investigate potential reasons for unfairness. Thus, the aim of this work was to analyze the effects of previously established sociodemographic-related confounders on classifier performance and explainability methods.

Approach
: A convolutional neural network (CNN) was trained to predict biological sex from T1-weighted brain MRI datasets of 4547 9- to 10-year-old adolescents from the Adolescent Brain Cognitive Development study. Performance disparities of the trained CNN between White and Black subjects were analyzed and saliency maps were generated for each subgroup at the intersection of sex and race.

Results
: The classification model demonstrated a significant difference in the percentage of correctly classified White male (90.3%±1.7%) and Black male (81.1%±4.5%) children. Conversely, slightly higher performance was found for Black female (89.3%±4.8%) compared with White female (86.5%±2.0%) children. Saliency maps showed subgroup-specific differences, corresponding to brain regions previously associated with pubertal development. In line with this finding, average pubertal development scores of subjects used in this study were significantly different between Black and White females (p<0.001) and males (p<0.001).

Conclusions
: We demonstrate that a CNN with significantly different sex classification performance between Black and White adolescents can identify different important brain regions when comparing subgroup saliency maps. Importance scores vary substantially between subgroups within brain structures associated with pubertal development, a race-associated confounder for predicting sex. We illustrate that unfair models can produce different XAI results between subgroups and that these results may explain potential reasons for biased performance.

Sex-specific genetic association between psychiatric disorders and cognition, behavior and brain imaging in children and adults

Gui Y, Zhou X, Wang Z, Zhang Y, Wang Z, Zhou G, Zhao Y, Liu M, Lu H, Zhao H. Sex-specific genetic association between psychiatric disorders and cognition, behavior and brain imaging in children and adults. Transl Psychiatry. 2022 Aug 26;12(1):347. doi: 10.1038/s41398-022-02041-6. PMID: 36028495.

Although there are pronounced sex differences for psychiatric disorders, relatively little has been published on the heterogeneity of sex-specific genetic effects for these traits until very recently for adults. Much less is known about children because most psychiatric disorders will not manifest until later in life and existing studies for children on psychiatric traits such as cognitive functions are underpowered. We used results from publicly available genome-wide association studies for six psychiatric disorders and individual-level data from the Adolescent Brain Cognitive Development (ABCD) study and the UK Biobank (UKB) study to evaluate the associations between the predicted polygenic risk scores (PRS) of these six disorders and observed cognitive functions, behavioral and brain imaging traits. We further investigated the mediation effects of the brain structure and function, which showed heterogeneity between males and females on the correlation between genetic risk of schizophrenia and fluid intelligence. There was significant heterogeneity in genetic associations between the cognitive traits and psychiatric disorders between sexes. Specifically, the PRSs of schizophrenia of boys showed stronger correlation with eight of the ten cognitive functions in the ABCD data set; whereas the PRSs of autism of females showed a stronger correlation with fluid intelligence in the UKB data set. Besides cognitive traits, we also found significant sexual heterogeneity in genetic associations between psychiatric disorders and behavior and brain imaging. These results demonstrate the underlying early etiology of psychiatric disease and reveal a shared and unique genetic basis between the disorders and cognition traits involved in brain functions between the sexes.

Adolescent Mental Health and Family Economic Hardships: The Roles of Adverse Childhood Experiences and Family Conflict

Barnhart S, Garcia AR, Karcher NR. Adolescent Mental Health and Family Economic Hardships: The Roles of Adverse Childhood Experiences and Family Conflict. J Youth Adolesc. 2022 Aug 23. doi: 10.1007/s10964-022-01671-9. Epub ahead of print. PMID: 35997913.

Rising and economically disproportionate rates of adverse mental health outcomes among children and youth warrant research investigating the complex pathways stemming from socioeconomic status. While adverse childhood experiences (ACEs) have been considered a possible mechanism linking socioeconomic status (SES) and child and youth psychopathology in previous studies, less is understood about how family environments might condition these pathways. Using data from a longitudinal, multiple-wave study, the present study addresses this gap by examining the direct relationships between family economic status and youth internalizing and externalizing symptoms, if ACEs mediate these relationships, and if conflictual family environments moderate these direct and indirect relationships. The data were obtained from 5510 youth participants [mean age at baseline = 9.52 (SD = 0.50), 47.7% female, 2.1% Asian, 10.3% Black, 17.6% Hispanic, 9.8% Multiracial/Multiethnic, 60.2% White] and their caretakers from the baseline, 1-year, and 2-year follow up waves. Conditional process analysis assessed the direct, indirect, and moderated relationships in separate, equivalent models based on youth- versus caregiver-raters of ACEs and youth psychopathology to capture potential differences based on the rater. The results of both the youth- and caregiver-rated models indicated that lower family economic status directly predicted higher levels of externalizing symptoms, and ACEs indirectly accounted for higher levels of internalizing and externalizing symptoms. Additionally, family conflict moderated some, but not all, of these relationships. The study’s findings highlight that lower family economic status and ACEs, directly and indirectly, contribute to early adolescent psychopathology, and conflictual family environments can further intensify these relationships. Implementing empirically supported policies and interventions that target ACEs and family environments may disrupt deleterious pathways between SES and youth psychopathology.

Obesity is associated with decreased gray matter volume in children: a longitudinal study

Jiang F, Li G, Ji W, Zhang Y, Wu F, Hu Y, Zhang W, Manza P, Tomasi D, Volkow ND, Gao X, Wang GJ, Zhang Y. Obesity is associated with decreased gray matter volume in children: a longitudinal study. Cereb Cortex. 2022 Aug 20:bhac300. doi: 10.1093/cercor/bhac300. Epub ahead of print. PMID: 35989308.

Childhood obesity has become a global health problem. Previous studies showed that childhood obesity is associated with brain structural differences relative to controls. However, few studies have been performed with longitudinal evaluations of brain structural developmental trajectories in childhood obesity. We employed voxel-based morphometry (VBM) analysis to assess gray matter (GM) volume at baseline and 2-year follow-up in 258 obese children (OB) and 265 normal weight children (NW), recruited as part of the National Institutes of Health Adolescent Brain and Cognitive Development study. Significant group × time effects on GM volume were observed in the prefrontal lobe, thalamus, right precentral gyrus, caudate, and parahippocampal gyrus/amygdala. OB compared with NW had greater reductions in GM volume in these regions over the 2-year period. Body mass index (BMI) was negatively correlated with GM volume in prefrontal lobe and with matrix reasoning ability at baseline and 2-year follow-up. In OB, Picture Test was positively correlated with GM volume in the left orbital region of the inferior frontal gyrus (OFCinf_L) at baseline and was negatively correlated with reductions in OFCinf_L volume (2-year follow-up vs. baseline). These findings indicate that childhood obesity is associated with GM volume reduction in regions involved with reward evaluation, executive function, and cognitive performance.

The ABCD stop signal data: Response to Bissett et al. Dev Cogn Neurosci

Garavan H, Chaarani B, Hahn S, Allgaier N, Juliano A, Yuan DK, Orr C, Watts R, Wager TD, Ruiz de Leon O, Hagler DJ Jr, Potter A. The ABCD stop signal data: Response to Bissett et al. Dev Cogn Neurosci. 2022 Aug 11;57:101144. doi: 10.1016/j.dcn.2022.101144. Epub ahead of print. PMID: 35987133.

This paper responds to a recent critique by Bissett et al. of the fMRI Stop task used in the Adolescent Brain Cognitive Development℠ Study (ABCD Study®). The critique focuses primarily on a task design feature related to race model assumptions (i.e., that the Go and Stop processes are fully independent). In response, we note that the race model is quite robust against violations of its assumptions. Most importantly, while Bissett raises conceptual concerns with the task we focus here on analyzes of the task data and conclude that the concerns appear to have minimal impact on the neuroimaging data (the validity of which do not rely on race model assumptions) and have far less of an impact on the performance data than the critique suggests. We note that Bissett did not apply any performance-based exclusions to the data they analyzed, a number of the trial coding errors they flagged were already identified and corrected in ABCD annual data releases, a number of their secondary concerns reflect sensible design decisions and, indeed, their own computational modeling of the ABCD Stop task suggests the problems they identify have just a modest impact on the rank ordering of individual differences in subject performance.

Adolescent-specific memory effects: evidence from working memory, immediate and long-term recognition memory performance in 8-30 yr olds

Skalaban LJ, Cohen AO, Conley MI, Lin Q, Schwartz GN, Ruiz-Huidobro NAM, Cannonier T, Martinez SA, Casey BJ. Adolescent-specific memory effects: evidence from working memory, immediate and long-term recognition memory performance in 8-30 yr olds. Learn Mem. 2022 Aug 11;29(8):223-233. doi: 10.1101/lm.053539.121. PMID: 35953104.

Working memory and recognition memory develop across adolescence, but the relationship between them is not fully understood. We investigated associations between n-back task performance and subsequent recognition memory in a community sample (8-30 yr, n = 150) using tasks from the Adolescent Brain Cognitive Development Study (ABCD Study) to cross-sectionally assess memory in an age range that will be sampled longitudinally. We added a 24-h delay condition to assess long-term recognition. Overall working memory, immediate and long-term recognition performance peaked in adolescence. Age effects in recognition memory varied by items (old targets, old distractors, and new items) and delay (0 and 24 h). For immediate recognition, accuracy was higher for targets and new items than for distractors, with accuracy for targets peaking in adulthood and accuracy for new items peaking during adolescence. For long-term recognition, adolescents’ accuracy was higher for targets than distractors, while adults showed similarly high accuracy for targets and distractors and children showed low accuracy for both. This pattern appeared to be specific to recognition of items from the high working memory load condition. The results suggest that working memory may facilitate long-term recognition of task-relevant over irrelevant items and may benefit the detection of new information during adolescence.

Longitudinal Assessments of Neurocognitive Performance and Brain Structure Associated With Initiation of Tobacco Use in Children

Dai HD, Doucet GE, Wang Y, Puga T, Samson K, Xiao P, Khan AS. Longitudinal Assessments of Neurocognitive Performance and Brain Structure Associated With Initiation of Tobacco Use in Children, 2016 to 2021. JAMA Netw Open. 2022;5(8):e2225991. doi:10.1001/jamanetworkopen.2022.25991

Importance  The landscape of tobacco use is changing. However, information about the association between early-age tobacco use and cognitive performances is limited, especially for emerging tobacco products such as electronic cigarettes (e-cigarettes).

Objective  To assess the association between early-age initiation of tobacco use and cognitive performances measured by the National Institutes of Health (NIH) Toolbox Cognitive Battery and to examine whether initiation is associated with differences in brain morphometry.

Design, Setting, and Participants  This observational cohort study examined the longitudinal associations of initiation of tobacco use with neurocognition using multivariate linear mixed models. Children aged 9 to 10 years from 21 US sites were enrolled in wave 1 (October 1, 2016, to October 31, 2018 [n = 11 729]) and the 2-year follow-up (August 1, 2018, to January 31, 2021 [n = 10 081]) of the Adolescent Brain Cognitive Development (ABCD) Study.

Exposures  Ever use (vs none) of any tobacco products at wave 1, including e-cigarettes, cigarettes, cigars, smokeless tobacco, hookah, pipes, and nicotine replacement.

Main Outcomes and Measures  Neurocognition measured by the NIH Toolbox Cognition Battery and morphometric measures of brain structure and region of interest analysis for the cortex from structural magnetic resonance imaging.

Results  Among 11 729 participants at wave 1 (mean [SE] age, 9.9 [0.6] years; 47.9% girls and 52.1% boys; 20.3% Hispanic; 14.9% non-Hispanic Black; and 52.1% non-Hispanic White), 116 children reported ever use of tobacco products. Controlling for confounders, tobacco ever users vs nonusers exhibited lower scores in the Picture Vocabulary Tests at wave 1 (b [SE] = −2.9 [0.6]; P < .001) and 2-year follow-up (b [SE] = −3.0 [0.7]; P < .001). The crystalized cognition composite score was lower among tobacco ever users than nonusers both at wave 1 (b [SE] = −2.4 [0.5]; P < .001) and 2-year follow-up (b [SE] = −2.7 [0.8]; P = .005). In structural magnetic resonance imaging, the whole-brain measures in cortical area and volume were significantly lower among tobacco users than nonusers, including cortical area (b [SE] = −5014.8 [1739.8] mm2P = .004) at wave 1 and cortical volume at wave 1 (b [SE] = −174 621.0 [5857.7] mm3P = .003) and follow-up (b [SE] = −21 790.8 [7043.9] mm3P = .002). Further region of interest analysis revealed smaller cortical area and volume in multiple regions across frontal, parietal, and temporal lobes at both waves.

Conclusions and Relevance  In this cohort study, initiating tobacco use in late childhood was associated with inferior cognitive performance and reduced brain structure with sustained effects at 2-year follow-up. These findings suggest that youths vulnerable to e-cigarettes and tobacco products should be treated as a priority population in tobacco prevention.

Integrative analysis of genomic and exposomic influences on youth mental health

Choi KW, Wilson M, Ge T, Kandola A, Patel CJ, Lee SH, Smoller JW. Integrative analysis of genomic and exposomic influences on youth mental health. J Child Psychol Psychiatry. 2022 Aug 10. doi: 10.1111/jcpp.13664. Epub ahead of print. PMID: 35946823.

Background: Understanding complex influences on mental health problems in young people is needed to inform early prevention strategies. Both genetic and environmental factors are known to influence youth mental health, but a more comprehensive picture of their interplay, including wide-ranging environmental exposures – that is, the exposome – is needed. We perform an integrative analysis of genomic and exposomic data in relation to internalizing and externalizing symptoms in a cohort of 4,314 unrelated youth from the Adolescent Brain and Cognitive Development (ABCD) Study.

Methods: Using novel GREML-based approaches, we model the variance in internalizing and externalizing symptoms explained by additive and interactive influences from the genome (G) and modeled exposome (E) consisting of up to 133 variables at the family, peer, school, neighborhood, life event, and broader environmental levels, including genome-by-exposome (G × E) and exposome-by-exposome (E × E) effects.

Results: A best-fitting integrative model with G, E, and G × E components explained 35% and 63% of variance in youth internalizing and externalizing symptoms, respectively. Youth in the top quintile of model-predicted risk accounted for the majority of individuals with clinically elevated symptoms at follow-up (60% for internalizing; 72% for externalizing). Of note, different domains of environmental exposures were most impactful for internalizing (life events) and externalizing (contextual including family, school, and peer-level factors) symptoms. In addition, variance explained by G × E contributions was substantially larger for externalizing (33%) than internalizing (13%) symptoms.

Conclusions: Advanced statistical genetic methods in a longitudinal cohort of youth can be leveraged to address fundamental questions about the role of ‘nature and nurture’ in developmental psychopathology.

Impact of Childhood Trauma Exposure, Genetic Variation in Endocannabinoid Signaling, and Anxiety on Frontolimbic Pathways in Children

Marusak HA, Evanski J, Desai S, Rabinak CA. Impact of Childhood Trauma Exposure, Genetic Variation in Endocannabinoid Signaling, and Anxiety on Frontolimbic Pathways in Children. Cannabis Cannabinoid Res. 2022 Aug 9. doi: 10.1089/can.2022.0144. Epub ahead of print. PMID: 35944262.

Introduction: The endocannabinoid (eCB) system plays a key role in modulating brain development, including myelination processes. Recent studies link a common variant (C385A, rs324420) in the fatty acid amide hydrolase (FAAH) gene to higher circulating eCB levels, lower anxiety, and altered frontolimbic development. Frontolimbic pathways, which demonstrate a protracted maturational course across childhood and adolescence, are associated with anxiety, and are vulnerable to environmental stressors such as trauma exposure. Here, we examined the impact of trauma exposure, FAAH genotype, and anxiety on frontolimbic white matter microstructure in children. Materials and Methods: We leveraged baseline data from the Adolescent Brain Cognitive Development (ABCD) study (n=9969; mean±standard deviation age=9.92±0.62 years; 47.1% female). Saliva samples were used for genotyping, and caregivers reported on their child’s anxiety symptoms and trauma exposure. Fractional anisotropy (FA), a nonspecific measure of white matter integrity, was estimated for frontolimbic tracts. Results: Thirty-six percent of youth experienced one or more potentially traumatic events according to DSM-5 Criterion A (64% controls), and 45% were FAAH A-allele carriers (55% noncarriers). Relative to controls, trauma-exposed youth demonstrated higher anxiety and higher FA of the left uncinate. The FAAH A-allele (vs. CC) was associated with lower FA in the left fornix and left parahippocampal cingulum, and there was an indirect effect of FAAH genotype on anxiety through FA of the left fornix. Moreover, genotype moderated the association between FA of the left cingulum and anxiety. Conclusions: Our findings demonstrate distinct effects of trauma exposure and the FAAH C385A variant on frontolimbic pathways and subsequent anxiety risk in preadolescent children. This line of work may provide important insights into neurodevelopmental mechanisms leading to anxiety risk, and potential targets for intervention.

Location matters: Regional variation in association of community burden of COVID-19 with caregiver and youth worry

Marshall AT, Hackman DA, Kan E, Abad S, Baker FC, Baskin-Sommers A, Dowling GJ, Gonzalez MR, Guillaume M, Kiss O, McCabe CJ, McCandliss BD, Pelham WE 3rd, Tapert SF, Van Rinsveld A, Sowell ER. Location matters: Regional variation in association of community burden of COVID-19 with caregiver and youth worry. Health Place. 2022 Aug 9;77:102885. doi: 10.1016/j.healthplace.2022.102885. Epub ahead of print. PMID: 35963164; PMCID: PMC9359938.

Our study characterized associations between three indicators of COVID-19’s community-level impact in 20 geographically diverse metropolitan regions and how worried youth and their caregivers in the Adolescent Brain Cognitive Development℠ Study have been about COVID-19. County-level COVID-19 case/death rates and monthly unemployment rates were geocoded to participants’ addresses. Caregivers’ (vs. youths’) COVID-19-related worry was more strongly associated with COVID-19’s community impact, independent of sociodemographics and pre-pandemic anxiety levels, with these associations varying by location. Public-health agencies and healthcare providers should avoid adopting uniform “one-size-fits-all” approaches to addressing COVID-19-related emotional distress and must consider specific communities’ needs, challenges, and strengths.

A prospective investigation of youth alcohol experimentation and reward responsivity in the ABCD study

May AC, Jacobus J, Simmons AN, Tapert SF. A prospective investigation of youth alcohol experimentation and reward responsivity in the ABCD study. Front Psychiatry. 2022 Aug 8;13:886848. doi: 10.3389/fpsyt.2022.886848. PMID: 36003980; PMCID: PMC9393480.

Rationale: Greater risk-taking behaviors, such as alcohol experimentation, are associated with different patterns of brain functioning in regions implicated in reward (nucleus accumbens, NA) and cognitive control (inferior frontal gyrus, IFG). These neural features have been observed in youth with greater risk-taking tendencies prior to substance use initiation, suggesting NA-IFG disruption may serve as an early marker for subsequent substance use disorders. Prospective studies are needed to determine if NA-IFG neural disruption predicts future substance use in school-age children, including those with minimal use of alcohol (e.g., sipping). The present large-sample prospective study sought to use machine learning to: (1) examine alcohol sipping at ages 9, 10 as a potential behavioral indicator of concurrent underlying altered neural responsivity to reward, and (2) determine if alcohol sipping and NA-IFG activation at ages 9, 10 can be used to predict which youth reported increased alcohol use at ages 11, 12. Additionally, low-level alcohol use and brain functioning at ages 9, 10 were examined as predictors of substance use and brain functioning at ages 11, 12.

Design and methods: This project used data from the baseline (Time 1) and two-year follow-up (Time 2) assessments of the Adolescent Brain Cognitive Development (ABCD) Study (Release 3.0). Support Vector Machine (SVM) learning determined if: (1) NA-IFG neural activity could correctly identify youth who reported alcohol sipping at Time 1 (n = 7409, mean age = 119.34 months, SD = 7.53; 50.27% female), and (2) NA-IFG and alcohol sipping frequency at Time 1 could correctly identify youth who reported drinking alcohol at Time 2 (n = 4000, mean age = 143.25 months, SD = 7.63; 47.53% female). Linear regression was also used to examine the relationship between alcohol sipping and NA-IFG activity at Time 1 and substance use and NA-IFG activity at Time 2. Data were also examined to characterize the environmental context in which youth first tried sips of alcohol (e.g., with or without parental permission, as part of a religious experience).

Results: Approximately 24% of the sample reported having tried sips of alcohol by ages 9, 10. On average, youth reported trying sips of alcohol 4.87 times (SD = 23.19) with age of first sip occurring at 7.36 years old (SD = 1.91). The first SVM model classified youth according to alcohol sipping status at Time 1 no better than chance with an accuracy of 0.35 (balanced accuracy = 0.52, sensitivity = 0.24, specificity = 0.80). The second SVM model classified youth according to alcohol drinking status at Time 2 with an accuracy of 0.76 (balanced accuracy = 0.56, sensitivity = 0.21, specificity = 0.91). Linear regression demonstrated that frequency of alcohol sipping at Time 1 predicted frequency of alcohol use at Time 2 (p < 0.001, adjusted R 2 = 0.075). Alcohol sipping at Time 1 was not linearly associated with NA or IFG activity at Time 2 (all ps > 0.05), and NA activity at Time 1 and Time 2 were not related (all ps > 0.05). Activity in the three subsections of the IFG at Time 1 predicted activity in those same regions at Time 2 (all ps < 0.02).

Conclusions and implications: Early sips of alcohol appear to predict alcohol use in early adolescence. Findings do not provide strong evidence for minimal early alcohol use (sipping) as a behavioral marker of underlying alterations in NA-IFG neural responsivity to reward. Improving our understanding of the neural and behavioral factors that indicate a greater propensity for future substance use is crucial for identifying at-risk youth and potential targets for preventative efforts.

Atypical Functional Network Properties and Associated Dimensions of Youth Psychopathology During Rest and Task Performance

Reimann GE, Stier AJ, Moore TM, et al. (In Press, 2022). Atypical Functional Network Properties and Associated Dimensions of Youth Psychopathology During Rest and Task Performance. Biological Psychiatry, Published: August 06, 2022, DOI:https://doi.org/10.1016/j.bpsgos.2022.07.007

Background
When brain networks deviate from typical development, this is thought to contribute to varying forms of psychopathology. However, research has been limited by the reliance on discrete diagnostic categories that overlook the potential for psychological comorbidity and the dimensional nature of symptoms.

Methods
The present study examined the topology of functional networks in association with four bifactor-defined psychopathology dimensions—general psychopathology, internalizing symptoms, conduct problems, and attention-deficit/hyperactivity disorder (ADHD) symptoms—via the Child Behavioral Checklist in a sample of 3,568 children from the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). Local and global graph theory metrics were calculated at rest and during tasks of reward processing, inhibition, and working memory.

Results
Greater ADHD symptoms were associated with reduced modularity across rest and tasks, as well as reduced local efficiency in motor networks at rest. Results survive sensitivity analyses for medication and socioeconomic status. Greater conduct problem symptoms were associated with reduced modularity on working memory and reward processing tasks; however, these results did not persist after sensitivity analyses. General psychopathology and internalizing symptoms showed no significant network associations.

Conclusions
Our findings suggest reduced efficiency in topology in those with greater ADHD symptoms across four critical cognitive states, with conduct problems also showing network deficits, although less consistently. This may suggest modularity deficits are a neurobiological marker of externalizing behavior in youth. Such specificity has not been demonstrated before using graph theory metrics and has the potential to redefine our understanding of network deficits in children with psychopathology symptoms.

Big or Little Data for Magnetic Resonance Imaging Research in Psychiatry?

Talati A, van Dijk MT, Weissman MM. Big or Little Data for Magnetic Resonance Imaging Research in Psychiatry? Biol Psychiatry. 2022 Aug 4:S0006-3223(22)01322-1. doi: 10.1016/j.biopsych.2022.06.007. Epub ahead of print. PMID: 35934545.

In recent years, there has been an impetus for larger magnetic resonance imaging (MRI) studies of brain function and disease to obtain more robust findings. A recent article by Marek et al. in Nature concluded that brain-wide association studies—studies “testing associations between individual variability in brain structure and function and cognitive or psychiatric symptoms”are currently underpowered and that casts of thousands are needed to obtain reproducible results. The study received considerable attention in the scientific community and an article in The New York Times Magazine. The implications touched the work of many psychiatric researchers who see MRI as a tool to finally understand brain function and mechanisms of neuropsychiatric disorders.
Prediction of fluid intelligence from T1-w MRI images: A precise two-step deep learning framework

Li M, Jiang M, Zhang G, Liu Y, Zhou X. Prediction of fluid intelligence from T1-w MRI images: A precise two-step deep learning framework. PLoS One. 2022 Aug 2;17(8):e0268707. doi: 10.1371/journal.pone.0268707. PMID: 35917308.

The Adolescent Brain Cognitive Development (ABCD) Neurocognitive Prediction Challenge (ABCD-NP-Challenge) is a community-driven competition that challenges competitors to develop algorithms to predict fluid intelligence scores from T1-w MRI images. In this work, a two-step deep learning pipeline is proposed to improve the prediction accuracy of fluid intelligence scores. In terms of the first step, the main contributions of this study include the following: (1) the concepts of the residual network (ResNet) and the squeeze-and-excitation network (SENet) are utilized to improve the original 3D U-Net; (2) in the segmentation process, the pixels in symmetrical brain regions are assigned the same label; (3) to remove redundant background information from the segmented regions of interest (ROIs), a minimum bounding cube (MBC) is used to enclose the ROIs. This new segmentation structure can greatly improve the segmentation performance of the ROIs in the brain as compared with the classical convolutional neural network (CNN), which yields a Dice coefficient of 0.8920. In the second stage, MBCs are used to train neural network regression models for enhanced nonlinearity. The fluid intelligence score prediction results of the proposed method are found to be superior to those of current state-of-the-art approaches, and the proposed method achieves a mean square error (MSE) of 82.56 on a test data set, which reflects a very competitive performance.

Using Explainable Artificial Intelligence to Discover Interactions in an Ecological Model for Obesity

Allen B, Lane M, Steeves EA, Raynor H. Using Explainable Artificial Intelligence to Discover Interactions in an Ecological Model for Obesity. Int J Environ Res Public Health. 2022 Aug 2;19(15):9447. doi: 10.3390/ijerph19159447. PMID: 35954804.

Ecological theories suggest that environmental, social, and individual factors interact to cause obesity. Yet, many analytic techniques, such as multilevel modeling, require manual specification of interacting factors, making them inept in their ability to search for interactions. This paper shows evidence that an explainable artificial intelligence approach, commonly employed in genomics research, can address this problem. The method entails using random intersection trees to decode interactions learned by random forest models. Here, this approach is used to extract interactions between features of a multi-level environment from random forest models of waist-to-height ratios using 11,112 participants from the Adolescent Brain Cognitive Development study. This study shows that methods used to discover interactions between genes can also discover interacting features of the environment that impact obesity. This new approach to modeling ecosystems may help shine a spotlight on combinations of environmental features that are important to obesity, as well as other health outcomes.

Prevalence of disordered eating and associations with sex, pubertal maturation, and weight in children in the US

Murray SB, Blashill AJ, Calzo JP. Prevalence of disordered eating and associations with sex, pubertal maturation, and weight in children in the US. JAMA Pediatrics (2022). Published online August 1, 2022. doi:10.1001/jamapediatrics.2022.2490, DOI: 10.1001/jamapediatrics.2022.2490.

Eating disorders often begin in adolescence, affecting more than 28 million people in the US,1 although the prevalence of disordered eating behaviors (DEBs) is even greater.1,2 Data on DEBs among children younger than age 12 years are scant. Ascertaining the prevalence of DEBs in children is critical because rapid maturational and weight-related changes in puberty are independently associated with DEBs,3 and some youth may experience different rates of growth and weight gain vs their peers. We sought to characterize DEB prevalence in US children aged 9 to 10 years and the associations of DEBs with sex, pubertal maturation, and weight.

Assessment of Parent Income and Education, Neighborhood Disadvantage, and Child Brain Structure

Rakesh D, Zalesky A, Whittle S. Assessment of Parent Income and Education, Neighborhood Disadvantage, and Child Brain Structure. JAMA Netw Open. 2022 Aug 1;5(8):e2226208. doi: 10.1001/jamanetworkopen.2022.26208. PMID: 35980639.

Importance: Although different aspects of socioeconomic status (SES) may represent distinct risk factors for poor mental health in children, knowledge of their differential and synergistic associations with the brain is limited.

Objective: To examine the independent associations between distinct SES factors and child brain structure.

Design, setting, and participants: We used baseline data from participants aged 9 to 10 years in the Adolescent Brain Cognitive Development (ABCD) study. These data were collected from 21 US sites between September 2017 and August 2018. Study participants were recruited from schools to create a participant sample that closely reflects the US population.

Exposures: Neighborhood disadvantage was measured using the area deprivation index. We also used data on total parent or caregiver educational attainment (in years) and household income-to-needs ratio.

Main outcomes and measures: T1-weighted magnetic resonance imaging was used to assess measures of cortical thickness, surface area, and subcortical volume.

Results: Data from 8862 ABCD participants aged 9 to 10 years were analyzed. The mean (SD) age was 119.1 (7.5) months; there were 4243 girls (47.9%) and 4619 boys (52.1%). Data on race or ethnicity were available for 8857 of 8862 participants: 173 (2.0%) were Asian, 1099 (12.4%) were Black or African American, 1688 (19.1%) were Hispanic, 4967 (56.1%) were White, and 930 (10.5%) reported multiple races or ethnicities. Using 10-fold, within-sample split-half replication, we found that neighborhood disadvantage was associated with lower cortical thickness in the following brain regions (η2 = 0.004-0.009): cuneus (B [SE] = -0.099 [0.013]; P < .001), lateral occipital (B [SE] = -0.088 [0.011]; P < .001), lateral orbitofrontal (B [SE] = -0.072 [0.012]; P < .001), lingual (B [SE] = -0.104 [0.012]; P < .001), paracentral (B [SE] = -0.086 [0.012]; P < .001), pericalcarine (B [SE] = -0.077 [0.012]; P < .001), postcentral (B [SE] = -0.069 [0.012]; P < .001), precentral (B [SE] = -0.059 [0.011]; P < .001), rostral middle frontal (B [SE] = -0.076 [0.011]; P < .001), and superior parietal (B [SE] = -0.060 [0.011]; P < .001). Exploratory analyses showed that the associations of low educational attainment or neighborhood disadvantage and low cortical thickness were attenuated in the presence of a high income-to-needs ratio (η2 = 0.003-0.007).

Conclusions and relevance: The findings of this cross-sectional study suggest that different SES indicators have distinct associations with children’s brain structure. A high income-to-needs ratio may play a protective role in the context of neighborhood disadvantage and low parent or caregiver educational attainment. This study highlights the importance of considering the joint associations of different SES indicators in future work.

‘Harmless’ adversarial network harmonization approach for removing site effects and improving reproducibility in neuroimaging studies

Yan W, Fu Z, Sui J, Calhoun VD. ‘Harmless’ adversarial network harmonization approach for removing site effects and improving reproducibility in neuroimaging studies. Annu Int Conf IEEE Eng Med Biol Soc. 2022 Jul;2022:1859-1862. doi: 10.1109/EMBC48229.2022.9871061. PMID: 36086519.

Multi-site collaboration, which gathers together samples from multiple sites, is a powerful way to overcome the small-sample problem in the neuroimaging field and has the potential to discover more robust and reproducible biomarkers. However, confounds among the datasets caused by various site-specific factors may dramatically reduce the cross-site reproducibility performance. To properly remove confounds while improving cross-site task performances, we propose a maximum classifier discrepancy generative adversarial network (MCD-GAN) that combines the advantages of generative models and maximum discrepancy theory. The mechanisms of MCD-GAN and how it harmonizes the dataset are visualized using simulated data. The performance of MCD-GAN was also compared with state-of-the-art methods (e.g., ComBat, cycle-GAN) within Adolescent Brain Cognitive Development (ABCD) dataset. Result demonstrates that the proposed MCD-GAN can effectively improve the cross-site gender classification performance by harmonizing site effects. Our proposed framework is also suitable for various classification/prediction tasks and is promising to facilitate the cross-site reproducibility of neuroimaging studies. Clinical Relevance- This work provides an efficient method for removing sites effects and improving reproducibility in large-cohort neuroimaging studies.

Functional Connectivity Stability: A Signature of Neurocognitive Development and Psychiatric Problems in Children

Fu Z, Salman MS, Liu J, Calhoun VD. Functional Connectivity Stability: A Signature of Neurocognitive Development and Psychiatric Problems in Children. Annu Int Conf IEEE Eng Med Biol Soc. 2022 Jul;2022:251-254. doi: 10.1109/EMBC48229.2022.9871390. PMID: 36085708.

Brain functional connectivity has been shown to provide a type of fingerprint for adult subjects. However, most studies tend to focus on the connectivity strength rather than its stability across scans. In this study, we performed for the first time a large-scale analysis of within-individual stability of functional connectivity (FC) using 9071 children from the Adolescent Brain Cognitive Development database. Functional network connectivity (FNC) was extracted via a fully automated independent component analysis framework. We found that children’s FNC is robust and stable with high similarity across scans and serves as a fingerprint that can identify an individual child from a large group. The robustness of this finding is supported by replicating the identification in the two-year follow-up session and between longitudinal sessions. More interestingly, we discovered that the within-individual FNC stability was predictive of cognitive performance and psychiatric problems in children, with higher FNC stability correlating with better cognitive performance and fewer dimensional psychopathology. The overall results indicate that the FNC of children also shows reliable within-individual stability, acting as a fingerprint for distinguishing participants, regardless of significant growth and development in the children’s brain. FC stability can be a valuable imaging marker to predict early cognitive and psychiatric behaviors in children. Clinical Relevance—The stability of functional connectivity can be used to identify children from a large group and to draw inferences on early-age cognitive and psychiatric behaviors.

Deep Learning Prediction and Visualization of Gender Related Brain Changes from Longitudinal Structural MRI Data in the ABCD Study

Bi Y, Abrol A, Fu Z, Calhoun V. Deep Learning Prediction and Visualization of Gender Related Brain Changes from Longitudinal Structural MRI Data in the ABCD Study. Annu Int Conf IEEE Eng Med Biol Soc. 2022 Jul;2022:3814-3817. doi: 10.1109/EMBC48229.2022.9871150. PMID: 36086576.

Deep learning algorithms for predicting from neuroimaging data have shown considerable promise. Deep learning models that take advantage of the data’s 3D structure have been proven to outperform ordinary machine learning on a number of learning tasks[1]. The majority of past research in this area, however, has focused on data from adults. Within the Adolescent Brain and Cognitive Development (ABCD) dataset, a major longitudinal development research, we examine the use of structural MRI data to predict gender and to identify gender related changes in brain structure. The results demonstrate that gender prediction accuracy is extremely high (>94%), and that this accuracy increases with age. Brain regions identified as the most discriminative in the task under study include predominantly frontal regions in addition to temporal lobe. When evaluating gender predictive changes specific to a two year increase in age, a broader set of visual, cingulate, and insular regions are revealed. Overall, our findings show a robust pattern of gender related structural brain changes, even over a small age range. This suggests the potential for evaluating the relationship of these changes to various behavioral and environmental factors to further study how the brain develops during adolescence. Clinical relevance- These results are not focused on clinical relevance currently, but in the future may be useful to characterize interactions between gender and potentially clinically relevant measures in adolescents.

Parental Arrest and Child Behavior: Differential Role of Executive Functioning among Racial Subgroups

Johnson EI, Planalp EM, Poehlmann-Tynan J. Parental Arrest and Child Behavior: Differential Role of Executive Functioning among Racial Subgroups. J Child Fam Stud. 2022 Jul;31(7):1933-1946. doi: 10.1007/s10826-022-02251-y. Epub 2022 Feb 7. PMID: 36187359; PMCID: PMC9518726.

This study examines relations among parental arrest, child executive functioning (EF), and problem behaviors among youth who participated in the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) study (N = 11,875). Participants ranged in age from 9 to 10 (M = 9.91) years, and approximately half were girls (47.9%). Results of regression analyses that controlled for sociodemographic risk factors indicated that children who experienced parental arrest exhibited more internalizing and externalizing behaviors than comparison youth, particularly when their mother vs. father had been arrested. Results of analyses that were disaggregated by child race further revealed that EF appeared to play a differential role among White (n = 5851) and Black (n = 1451) children. Among White children, EF was associated with fewer internalizing and externalizing behaviors regardless of whether or not a parent had been arrested. Among Black children, low levels of EF were associated with more internalizing behaviors in the context of parental arrest vs. no arrest, but high levels of EF did not appear to confer benefits. EF was not significantly related to externalizing behaviors among Black children. Taken together, results suggest that parental arrests have adverse implications for child well-being that warrant continued theoretical and empirical attention. Findings also suggest that, although EF may be broadly beneficial among White children, there appear to be constraints on the extent to which high EF benefits Black children, a finding that is discussed through the lens of racial stratification and that has important implications for future theory, research, and practice.

Socioeconomic disadvantage and episodic memory ability in the ABCD sample: Contributions of hippocampal subregion and subfield volumes

Botdorf M, Dunstan J, Sorcher L, Dougherty LR, Riggins T. Socioeconomic disadvantage and episodic memory ability in the ABCD sample: Contributions of hippocampal subregion and subfield volumes. Developmental Cognitive Neuroscience, Volume 57, October 2022, 101138, https://doi.org/10.1016/j.dcn.2022.101138.

Socioeconomic disadvantage is associated with volumetric differences in stress-sensitive neural structures, including the hippocampus, and deficits in episodic memory. Rodent studies provide evidence that memory deficits arise via stress-related structural differences in hippocampal subdivisions; however, human studies have only provided limited evidence to support this notion. We used a sample of 10,695 9–13-year-old participants from two timepoints of the Adolescent Brain and Cognitive Development (ABCD) Study to assess whether socioeconomic disadvantage relates to episodic memory performance through hippocampal volumes. We explored associations among socioeconomic disadvantage, measured via the Area Deprivation Index (ADI), concurrent subregion (anterior, posterior) and subfield volumes (CA1, CA3, CA4/DG, subiculum), and episodic memory, assessed via the NIH Toolbox Picture Sequence Memory Test at baseline and 2-year follow-up (Time 2). Results showed that higher baseline ADI related to smaller concurrent anterior, CA1, CA4/DG, and subiculum volumes and poorer Time 2 memory performance controlling for baseline memory. Moreover, anterior, CA1, and subiculum volumes mediated the longitudinal association between the ADI and memory. Results suggest that greater socioeconomic disadvantage relates to smaller hippocampal subregion and subfield volumes and less age-related improvement in memory. These findings shed light on the neural mechanisms linking socioeconomic disadvantage and cognitive ability in childhood.

Longitudinally stable, brain-based predictive models mediate the relationships between childhood cognition and socio-demographic, psychological and genetic factors

Pat N, Wang Y, Anney R, Riglin L, Thapar A, Stringaris A. Longitudinally stable, brain-based predictive models mediate the relationships between childhood cognition and socio-demographic, psychological and genetic factors. Hum Brain Mapp. 2022 Jul 28. doi: 10.1002/hbm.26027. Epub ahead of print. PMID: 35903877.

Cognitive abilities are one of the major transdiagnostic domains in the National Institute of Mental Health’s Research Domain Criteria (RDoC). Following RDoC’s integrative approach, we aimed to develop brain-based predictive models for cognitive abilities that (a) are developmentally stable over years during adolescence and (b) account for the relationships between cognitive abilities and socio-demographic, psychological and genetic factors. For this, we leveraged the unique power of the large-scale, longitudinal data from the Adolescent Brain Cognitive Development (ABCD) study (n ~ 11 k) and combined MRI data across modalities (task-fMRI from three tasks: resting-state fMRI, structural MRI and DTI) using machine-learning. Our brain-based, predictive models for cognitive abilities were stable across 2 years during young adolescence and generalisable to different sites, partially predicting childhood cognition at around 20% of the variance. Moreover, our use of ‘opportunistic stacking’ allowed the model to handle missing values, reducing the exclusion from around 80% to around 5% of the data. We found fronto-parietal networks during a working-memory task to drive childhood-cognition prediction. The brain-based, predictive models significantly, albeit partially, accounted for variance in childhood cognition due to (1) key socio-demographic and psychological factors (proportion mediated = 18.65% [17.29%-20.12%]) and (2) genetic variation, as reflected by the polygenic score of cognition (proportion mediated = 15.6% [11%-20.7%]). Thus, our brain-based predictive models for cognitive abilities facilitate the development of a robust, transdiagnostic research tool for cognition at the neural level in keeping with the RDoC’s integrative framework.

Contemporary screen time modalities and disruptive behavior disorders in children: a prospective cohort study

Nagata JM, Chu J, Ganson KT, Murray SB, Iyer P, Gabriel KP, Garber AK, Bibbins-Domingo K, Baker FC. Contemporary screen time modalities and disruptive behavior disorders in children: a prospective cohort study. J Child Psychol Psychiatry. 2022 Jul 26. doi: 10.1111/jcpp.13673. Epub ahead of print. PMID: 35881083.

Background: Cross-sectional studies have demonstrated associations between screen time and disruptive behavior disorders (conduct disorder and oppositional defiant disorder); however, prospective associations remain unknown. This study’s objective was to determine the prospective associations of contemporary screen time modalities with conduct and oppositional defiant disorder in a national cohort of 9-11-year-old children.

Methods: We analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11,875). Modified Poisson regression analyses were conducted to estimate the associations between baseline child-reported screen time (total and by modality) and parent-reported conduct or oppositional defiant disorder based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5) at 1-year follow-up, adjusting for potential confounders.

Results: Participants reported an average of 4 hr of total screen time per day at baseline. Each hour of total screen time per day was prospectively associated with a 7% higher prevalence of conduct disorder (95% CI 1.03-1.11) and a 5% higher prevalence of oppositional defiant disorder (95% CI 1.03-1.08) at 1-year follow-up. Each hour of social media per day was associated with a 62% higher prevalence of conduct disorder (95% CI 1.39-1.87). Each hour of video chat (prevalence ratio [PR] 1.21, 95% CI 1.06-1.37), texting (PR 1.19, 95% CI 1.07-1.33), television/movies (PR 1.17, 95% CI 1.10-1.25), and video games (PR 1.14, 95% CI 1.07-1.21) per day was associated with a higher prevalence of the oppositional defiant disorder. When examining thresholds, exposure to >4 hr of total screen time per day was associated with a higher prevalence of conduct disorder (69%) and oppositional defiant disorder (46%).

Conclusions: Higher screen time was prospectively associated with a higher prevalence of new-onset disruptive behavior disorders. The strongest association was between social media and conduct disorder, indicating that future research and interventions may focus on social media platforms to prevent conduct disorder.

Prevalence of Mental Health Problems in Transgender Children Aged 9 to 10 Years in the US, 2018

Russell DH, Hoq M, Coghill D, Pang KC (2022). Prevalence of Mental Health Problems in Transgender Children Aged 9 to 10 Years in the US, 2018. Research Letter, Research Letter, Diversity, Equity, and Inclusion. JAMA Netw Open. 2022;5(7):e2223389. doi:10.1001/jamanetworkopen.2022.23389

Discussion

Previous research using clinical samples of transgender children aged 5 to 11 years reported lower rates of depression and anxiety than we observed in this cohort study. Apart from methodological differences in assessing mental health, a possible reason for this disparity is that transgender children attending specialist gender clinics are likely to have support from their families (a key protective factor for the mental health of transgender young people); in comparison, many transgender children in the general population lack parental support for their gender.

Previous studies using clinical and convenience samples of transgender adolescents had higher rates of depression and anxiety compared with our sample. This is consistent with earlier clinic-based observations that transgender children have lower rates of anxiety and depression compared with transgender adolescents, which may be explained by observations from the general population that depression and anxiety more frequently develop during adolescence.

The small number of transgender participants is a limitation of our study, as is the exclusion of many children who did not understand the question on gender identity. Nevertheless, this is, to our knowledge, the first study to report rates of DSM-5–related problems using a representative population sample of transgender children. Our findings suggest that by 9 to 10 years of age transgender children already show increased susceptibility to mental health problems compared with their cisgender peers, which has important public health implications. Whether this is due to stigma, minority stress, discrimination, or gender dysphoria is unclear, but providing appropriate mental health supports to this vulnerable group is paramount.

Effect of exposure to maternal diabetes during pregnancy on offspring’s brain cortical thickness and neurocognitive functioning

Ahmed S, Cano MA, Sánchez M, Hu N, Ibañez G. Effect of exposure to maternal diabetes during pregnancy on offspring’s brain cortical thickness and neurocognitive functioning. Child Neuropsychology, Published online: 22 Jul 2022.

Little is known about the long-term effects of maternal diabetes during pregnancy (DP), either gestational diabetes or preexisting diabetes (type 1 or type 2), on offspring’s brain morphometry and neurocognitive functioning (NCF). This study examined the effect of prenatal exposure to maternal DP on the brain structure and NCF in children between 9 and 10 years of age. This study used cross-sectional neuroimaging and NCF data from the baseline wave of the Adolescent Brain and Cognitive Development® study. Exposure to maternal DP was assigned from the developmental history questionnaire. Differences in the brain cortical thickness (CTh) and five cognitive abilities (executive function, working and episodic memory, processing speed, and language abilities) were examined in diabetes-exposed and diabetes-unexposed children. Linear mixed effect models and generalized linear models were used to adjust for the effect of confounding variables. A total of 9,967 children (718 diabetes-exposed and 9249 unexposed) were included in the analysis. Diabetes-exposed children had lower whole-brain CTh [mean: exposed vs unexposed = 2.725 mm vs 2.732 mm; difference (95%CI): −0.007 mm (−0.013, −0.001)] compared to unexposed children after adjusting for confounding variables. Diabetes-exposed children had lower CTh in most part of the occipital lobe of both hemispheres, right postcentral gyrus, and left superior parietal cortex. Diabetes-exposed children also had lower scores in processing speed task [mean difference (95%CI): −1.7 (−2.8, −0.6)] and total cognition [mean difference (95%CI): −0.6 (−1.2, −0.02)]. Diabetes-exposed children have reduced CTh and NCF during preadolescence, which might have implications for psychomotor development during later life. Prospective studies are needed to confirm our findings.

Disparities in sleep duration among American children: effects of race and ethnicity, income, age, and sex

Giddens NT, Juneau P, Manza P, Volkow ND (2022). Disparities in sleep duration among American children: effects of race and ethnicity, income, age, and sex. PNAS, July 18, 2022. https://doi.org/10.1073/pnas.2120009119

Significance
Sleep deprivation is detrimental to a child’s health. Access to actigraphy measures enabled us to assess racial/ethnic and income group differences in sleep in a large data set from the Adolescent Brain Cognitive Development study (4,207 children ages 9 to 13). This method relies on the closed algorithm of the commercial Fitbit device. Our analyses revealed that black children and low-income children slept significantly less than children from other groups. These findings indicate that disparities in sleep time among children are driven in part by socioeconomic factors.

Abstract

Children in the United States sleep less than the recommended amount and sleep deficiencies may be worse among disadvantaged children. Prior studies that compared sleep time in children of different race/ethnic groups mostly relied on questionnaires or were limited to small sample sizes. Our study takes advantage of the Adolescent Brain Cognitive Development study to compare total sleep time using a week of actigraphy data among American children (n = 4,207, 9 to 13 y old) of different racial/ethnic and income groups. We also assessed the effects of neighborhood deprivation, experience of discrimination, parent’s age at child’s birth, body mass index (BMI), and time the child fell asleep on sleep times. Daily total sleep time for the sample was 7.45 h and race/ethnicity, income, sex, age, BMI, were all significant predictors of total sleep time. Black children slept less than White children (∼34 min; Cohen’s d = 0.95), children from lower income families slept less than those from higher incomes (∼16 min; Cohen’s d = 0.44), boys slept less than girls (∼7 min; Cohen’s d = 0.18), and older children slept less than younger ones (∼32 min; Cohen’s d = 0.91); mostly due to later sleep times. Children with higher BMI also had shorter sleep times. Neither area deprivation index, experience of discrimination, or parent’s age at child’s birth significantly contributed to sleep time. Our findings indicate that children in the United States sleep significantly less than the recommended amount for healthy development and identifies significant racial and income disparities. Interventions to improve sleep hygiene in children will help improve health and ameliorate racial disparities in health outcomes.

Genetic Association of Attention-Deficit/Hyperactivity Disorder and Major Depression With Suicidal Ideation and Attempts in Children: The Adolescent Brain Cognitive Development Study

Lee PH, Doyle AE, Li X, Silberstein M, Jung JY, Gollub RL, Nierenberg AA, Liu RT, Kessler RC, Perlis RH, Fava M. Genetic Association of Attention-Deficit/Hyperactivity Disorder and Major Depression With Suicidal Ideation and Attempts in Children: The Adolescent Brain Cognitive Development Study. Biol Psychiatry. 2022 Aug 1;92(3):236-245. doi: 10.1016/j.biopsych.2021.11.026. Epub 2021 Dec 22.

Background: Suicide is among the leading causes of death in children and adolescents. There are well-known risk factors of suicide, including childhood abuse, family conflicts, social adversity, and psychopathology. While suicide risk is also known to be heritable, few studies have investigated genetic risk in younger individuals.

Methods: Using polygenic risk score analysis, we examined whether genetic susceptibility to major psychiatric disorders is associated with suicidal behaviors among 11,878 children enrolled in the ABCD (Adolescent Brain Cognitive Development) Study. Suicidal ideation and suicide attempt data were assessed using the youth report of the Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5. After performing robust quality control of genotype data, unrelated individuals of European descent were included in analyses (n = 4344).

Results: Among 8 psychiatric disorders we examined, depression polygenic risk scores were associated with lifetime suicide attempts both in the baseline (odds ratio = 1.55, 95% CI = 1.10-2.18, p = 1.27 × 10-2) and in the follow-up year (odds ratio = 1.38, 95% CI = 1.08-1.77, p = 1.05 × 10-2), after adjusting for children’s age, sex, socioeconomic backgrounds, family history of suicide, and psychopathology. In contrast, attention-deficit/hyperactivity disorder polygenic risk scores were associated with lifetime suicidal ideation (odds ratio = 1.15, 95% CI = 1.05-1.26, p = 3.71 × 10-3), suggesting a distinct contribution of the genetic risk underlying attention-deficit/hyperactivity disorder and depression on suicidal behaviors of children.

Conclusions: The largest genetic sample of suicide risk data in U.S. children suggests a significant genetic basis of suicide risk related to attention-deficit/hyperactivity disorder and depression. Further research is warranted to examine whether incorporation of genomic risk may facilitate more targeted screening and intervention efforts.

Application of the RDoC Framework to Predict Alcohol Use and Suicidal Thoughts and Behaviors among Early Adolescents in the Adolescent Brain and Cognitive Development (ABCD) Study

Aguinaldo LD, Coronado C, Gomes DA, Courtney KE, Jacobus J. Application of the RDoC Framework to Predict Alcohol Use and Suicidal Thoughts and Behaviors among Early Adolescents in the Adolescent Brain and Cognitive Development (ABCD) StudyBrain Sciences. 2022; 12(7):935. https://doi.org/10.3390/brainsci12070935

Alcohol use confers risk for suicidal thoughts and behaviors (ideation, attempt) in early adolescents. The Research Domain Criteria provides a framework for examination of multidimensional and modifiable risk factors. We examined distinct latent profiles based on patterns of positive valence (reward responsivity) and cognitive systems (neurocognition) from the ABCD Study (age 9–10, N = 10,414) at baseline enrollment. Longitudinal associations were determined between baseline positive valence and cognitive profiles and group classification (alcohol use, suicidal thoughts and behaviors, or their co-occurrence) two-years after initial assessment (ages 11–12). Three unique profiles of positive valence, cognition, alcohol use, and suicidal thoughts and behaviors were identified. Two baseline profiles predicted alcohol use and suicidal thoughts and behaviors, two-years after initial assessment. Low positive valence with high cognition (but low impulsivity) predicted alcohol use (OR = 1.414, p< 0.001), while high positive valence with low cognition (but high impulsivity) predicted suicidal thoughts and behaviors (OR = 1.25, p = 0.038), compared to average positive valence and cognition. Unique profiles of positive valence and cognitive systems among 9–12-year-olds may be predictive of alcohol use and suicidal thoughts and behaviors over a two-year period. Findings underscore the potential for trajectory research on positive valence and cognitive profiles to enhance prevention for early-adolescents.

Associations Between Adverse Childhood Experiences, Adolescent Screen Time and Physical Activity During the COVID-19 Pandemic

Raney J, Testa A, Jackson DB, Ganson KT, Nagata J. Associations Between Adverse Childhood Experiences, Adolescent Screen Time and Physical Activity During the COVID-19 Pandemic. Acad Pediatr. 2022 Jul 16:S1876-2859(22)00352-7. doi: 10.1016/j.acap.2022.07.007. Epub ahead of print. PMID: 35853601; PMCID: PMC9288265.

Objective: To determine the associations between Adverse Childhood Experiences (ACEs), adolescent screen time, and physical activity during the early COVID-19 pandemic.

Methods: Data (2016-2020) from the Adolescent Brain Cognitive Development (ABCD) study were analyzed. Linear regression analyses estimated associations between ACE score and screen time and physical activity in May 2020, adjusting for potential confounders.

Results: Of the 6,749 adolescent respondents primarily aged 12-13, 81.6% reported a history of one ACE or more. In adjusted models, a higher ACE score was significantly associated with greater hours per day of screen time, with youth with ≥4 ACEs associated with 2.3 more hours of screen time per day compared to youth with 0 ACEs. In addition, the adjusted models found that a higher ACE score was associated with lower physical activity; youth with ≥4 ACEs averaged 0.8 fewer hours per week of physical activity and 0.5 fewer days per week of 60 minutes of physical activity compared to youth with 0 ACEs. Gender and race were also significantly associated with changes in screen time and physical activity.

Conclusions: ACEs are associated with higher adolescent sedentary behaviors, particularly greater screen time, during the early COVID-19 pandemic (May 2020). Clinicians caring for youth exposed to trauma in the post-pandemic environment should explore screen time and physical activity behaviors.

Proportional intracranial volume correction differentially biases behavioral predictions across neuroanatomical features, sexes, and development

Dhamala E, Ooi LQR, Chen J, Kong R, Anderson KM, Chin R, Yeo BTT, Holmes AJ. Proportional intracranial volume correction differentially biases behavioral predictions across neuroanatomical features, sexes, and development. Neuroimage. 2022 Jul 14:119485. doi: 10.1016/j.neuroimage.2022.119485. Epub ahead of print. PMID: 35843514.

Individual differences in brain anatomy can be used to predict variations in cognitive ability. Most studies to date have focused on broad population-level trends, but the extent to which the observed predictive features are shared across sexes and age groups remains to be established. While it is standard practice to account for intracranial volume (ICV) using proportion correction in both regional and whole-brain morphometric analyses, in the context of brain-behavior predictions the possible differential impact of ICV correction on anatomical features and subgroups within the population has yet to be systematically investigated. In this work, we evaluate the effect of proportional ICV correction on sex-independent and sex-specific predictive models of individual cognitive abilities across multiple anatomical properties (surface area, gray matter volume, and cortical thickness) in healthy young adults (Human Connectome Project; n=1013, 548 females) and typically developing children (Adolescent Brain Cognitive Development study; n=1823, 979 females). We demonstrate that ICV correction generally reduces predictive accuracies derived from surface area and gray matter volume, while increasing predictive accuracies based on cortical thickness in both adults and children. Furthermore, the extent to which predictive models generalize across sexes and age groups depends on ICV correction: models based on surface area and gray matter volume are more generalizable without ICV correction, while models based on cortical thickness are more generalizable with ICV correction. Finally, the observed neuroanatomical features predictive of cognitive abilities are unique across age groups regardless of ICV correction, but whether they are shared or unique across sexes (within age groups) depends on ICV correction. These findings highlight the importance of considering individual differences in ICV, and show that proportional ICV correction does not remove the effects of cranial volume from anatomical measurements and can introduce ICV bias where previously there was none. ICV correction choices affect not just the strength of the relationships captured, but also the conclusions drawn regarding the neuroanatomical features that underlie those relationships.

COVID information and masking behaviors in U.S. adolescents: Findings from the Adolescent Brain Cognitive Development (ABCD) Study

Nagata JM, Ganson KT, Liu J, Patel KP Tai JC, Murray SB, Bibbins-Domingo K. (2022). COVID information and masking behaviors in U.S. adolescents: Findings from the Adolescent Brain Cognitive Development (ABCD) Study. Preventive Medicine Reports. Volume 28, August 2022, 101900. https://doi.org/10.1016/j.pmedr.2022.101900

Adolescents are particularly vulnerable to health misinformation and are at risk for suboptimal adherence to protective health behaviors in the COVID-19 pandemic. Guided by factors consistent with the theories of planned behavior and rumor transmission, this study sought to analyze the impact of multiple information sources, including social media, television media, internet and parental counseling, on masking behaviors in adolescents. Responses from the December 2020 COVID-19 survey, representing 4,106 U.S. adolescents ages 12–14 from the Adolescent Brain Cognitive Development Study (ABCD) were analyzed. The majority of parents (61.1%) reported counseling their children on the importance of wearing masks all the time in the past week. A minority of adolescents reported more than one hour of daily exposure to COVID-19 related information on social media (9.1%), the internet (4.3%) and television (10.2%). In unadjusted and adjusted models, greater frequency of parental counseling and exposure to COVID-19 television or social media were associated with ‘always masking’ behaviors. Our findings provide support for the importance of parent counseling and suggest that socialmedia and television may overall support rather than dissuade protective COVID-19 health behaviors in adolescents.

Nucleus Accumbens Response to Reward among Children with a Family History of Alcohol Use Problems: Convergent Findings from the ABCD Study® and Michigan Longitudinal Study

Martz ME, Hardee JE, Cope LM, McCurry KL, Soules M, Zucker RA, Heitzeg MM. Nucleus Accumbens Response to Reward among Children with a Family History of Alcohol Use Problems: Convergent Findings from the ABCD Study® and Michigan Longitudinal Study. Brain Sciences. 2022; 12(7):913. https://doi.org/10.3390/brainsci12070913

Having a family history of alcohol use problems (FH+) conveys risk for alcohol use in offspring. Reward-related brain functioning may play a role in this vulnerability. The present study investigated brain function in the nucleus accumbens (NAcc) associated with the anticipation of reward in youth with two biological parents with alcohol use problems (FH+2), one biological parent with alcohol use problems (FH+1), and no biological parents with alcohol use problems (FH-). Participants were from the large, national Adolescent Brain Cognitive Development (ABCD) Study (mean age: 9.93; 48% female; FH+2 n = 223, FH+1 n = 1447, FH- n = 9690) and the Michigan Longitudinal Study (MLS), consisting of community-recruited families with high rates of alcohol use disorder (mean age: 10.54; 39.3% female; FH+2 n = 40, FH+1 n = 51, FH- n = 40). Reward anticipation was measured by the monetary incentive delay task. Regression models were used to assess associations between FH status and the anticipation of large rewards in right and left NAcc regions of interest. In both studies, FH+2 youth showed blunted anticipatory reward responding in the right NAcc compared to FH+1 youth. In the MLS, FH+2 youth also had blunted anticipatory reward responding in the right NAcc compared to the FH- group. Convergent results across two separate samples provide insights into a unique vulnerability of FH+2 youth and suggest that binary FH+ versus FH- categorizations may obscure important differences within FH+ youth.

Social Epidemiology of Early Adolescent Cyberbullying in the United States

Nagata JM, Trompeter N, Singh G, Ganson KT, Testa A, Jackson DB, Assari S, Murray SB, Bibbins-Domingo K, Baker FC. Social Epidemiology of Early Adolescent Cyberbullying in the United States. Acad Pediatr. 2022 Jul 12:S1876-2859(22)00347-3. doi: 10.1016/j.acap.2022.07.003. Epub ahead of print. PMID: 35840085.

Objective: To determine the prevalence and sociodemographic correlates of cyberbullying victimization and perpetration among a racially/ethnically and socioeconomically diverse population-based sample of 11-12-year-old early adolescents.

Methods: We analyzed cross-sectional data from the Adolescent Brain Cognitive Development (ABCD) Study (Year 2; N=9,429). Multiple logistic regression analyses were used to estimate associations between sociodemographic factors (sex, race/ethnicity, sexual orientation, country of birth, household income, parental education) and adolescent-reported cyberbullying victimization and perpetration.

Results: In the overall sample, lifetime prevalence of cyberbullying victimization was 9.6%, with 65.8% occurring in the past 12 months, while lifetime prevalence of cyberbullying perpetration was 1.1%, with 59.8% occurring the past 12 months. Boys reported higher odds of cyberbullying perpetration (AOR 1.71, 95% CI 1.01-2.92) but lower odds of cyberbullying victimization (AOR 0.80, 95% CI 0.68-0.94) than girls. Sexual minorities reported 2.83 higher odds of cyberbullying victimization (95% CI 1.69-4.75) than non-sexual minorities. Lower household income was associated with 1.64 (95% CI 1.34-2.00) higher odds of cyberbullying victimization than higher household income, however household income was not associated with cyberbullying perpetration. Total screen time, particularly on the internet and social media, was associated with both cyberbullying victimization and perpetration.

Conclusions: Nearly one in ten early adolescents reported cyberbullying victimization. Pediatricians, parents, teachers, and online platforms can provide education to support victims and prevent perpetration for early adolescents at the highest risk of cyberbullying.

Brain structural covariation linked to screen media activity and externalizing behaviors in children

Zhao Y, Paulus M, Bagot KS, Constable RT, Yaggi HK, Redeker NS, Potenza MN. Brain structural covariation linked to screen media activity and externalizing behaviors in children. Journal of Behavioral Addictions. Online publication date 30 Jun 2022, https://doi.org/10.1556/2006.2022.00044

Background and Aims
Screen media activity (SMA) may impact neurodevelopment in youth. Cross-sectionally, SMA has been linked to brain structural patterns including cortical thinning in children. However, it remains unclear whether specific brain structural co-variation patterns are related to SMA and other clinically relevant measures such as psychopathology, cognition and sleep in children.

Methods
Adolescent Brain Cognitive Development (ABCD) participants with useable baseline structural imaging (N = 10,691; 5,107 girls) were analyzed. We first used the Joint and Individual Variation Explained (JIVE) approach to identify cortical and subcortical covariation pattern(s) among a set of 221 brain features (i.e., surface area, thickness, or cortical and subcortical gray matter (GM) volumes). Then, the identified structural covariation pattern was used as a predictor in linear mixed-effect models to investigate its associations with SMA, psychopathology, and cognitive and sleep measures.

Results
A thalamus-prefrontal cortex (PFC)-brainstem structural co-variation pattern (circuit) was identified. The pattern suggests brainstem and bilateral thalamus proper GM volumes covary more strongly with GM volume and/or surface area in bilateral superior frontal gyral, rostral middle frontal, inferior parietal, and inferior temporal regions. This covariation pattern highly resembled one previously linked to alcohol use initiation prior to adulthood and was consistent in girls and boys. Subsequent regression analyses showed that this co-variation pattern associated with SMA (β = 0.107, P = 0.002) and externalizing psychopathology (β = 0.117, P = 0.002), respectively.

Discussion and Conclusions
Findings linking SMA-related structural covariation to externalizing psychopathology in youth resonate with prior studies of alcohol-use initiation and suggest a potential neurodevelopmental mechanism underlying addiction vulnerability.

Individual-, peer-, and parent-level substance use-related factors among 9- and 10-year-olds from the ABCD Study: Prevalence rates and sociodemographic differences

Martz ME, Heitzeg MM, Lisdahl KM, Cloak CC, Feldstein Ewing SW, Gonzalez R, Haist F, LeBlanc KH, Madden PA, Megan Ross J, Sher KJ, Tapert SF, Thompson WK, Wade NE. Individual-, peer-, and parent-level substance use-related factors among 9- and 10-year-olds from the ABCD Study: Prevalence rates and sociodemographic differences. Drug and Alcohol Dependence Reports
Volume 3, June 2022, 100037. https://doi.org/10.1016/j.dadr.2022.100037

Background
Although a relatively large body of research has identified multiple factors associated with adolescent substance use, less is known about earlier substance-related factors during preadolescence, including curiosity to use substances. The present study examined individual-, peer-, and parent-level domains pertaining to substance use and how these domains vary by sociodemographic subgroups and substance type.

Methods
Participants were 11,864 9- and 10-year-olds from the baseline sample of the Adolescent Brain Cognitive Development (ABCD) Study. Youth-reported measures were curiosity to use substances and perceived peer substance use. Parent-reported measures were availability of and rules about substances. Generalized logistic mixed models (GLMM) were used to compare these measures across alcohol, nicotine, and marijuana and across sociodemographic subgroupings (sex, race/ethnicity, household income, and family history of alcohol problems). GLMM was then used to examine predictors of curiosity to use by substance type.

Results
The most striking descriptive differences were found between race/ethnicity and income categories (e.g., positive associations between greater income and greater availability of alcohol). In multivariable analyses, greater curiosity to use alcohol was associated with being male, higher household income, perceived peer alcohol use, and easy alcohol availability; greater curiosity to use nicotine was associated with being male, perceived peer cigarette use, easy availability of cigarettes, and no parental rules about cigarette use.

Conclusions
This study identified substance use-related individual-, peer-, and parent-level factors among a diverse, national sample. Findings highlight the importance of considering sociodemographic and substance-specific variability and may help identify risk and protective factors preceding adolescent substance use.

Social epidemiology of early adolescent problematic screen use in the United States

Nagata JM, Singh G, Sajjad OM, Ganson KT, Testa A, Jackson DB, Assari S, Murray SB, Bibbins-Domingo K, Baker FC. Social epidemiology of early adolescent problematic screen use in the United States. Pediatr Res. 2022 Jun 29. doi: 10.1038/s41390-022-02176-8. Epub ahead of print. PMID: 35768491.

Objective: To determine sociodemographic correlates of problematic screen use (social media, video games, mobile phones) among a racially/ethnically and socioeconomically diverse population-based sample of 10-14-year-old early adolescents.

Study design: We analyzed cross-sectional data from the Adolescent Brain Cognitive Development Study (Year 2, 2018-2020; N = 8753). Multiple linear regression analyses were used to estimate associations between sociodemographic factors (age, sex, race/ethnicity, primary language, household income, parental education) and adolescent-reported problematic video game (Video Game Addiction Questionnaire), social media (Social Media Addiction Questionnaire), and mobile phone use (Mobile Phone Involvement Questionnaire).

Results: Boys reported higher problematic video game use while girls reported higher problematic social media and mobile phone use. Native American, black, and Latinx adolescents reported higher scores across all problematic screen measures compared to non-Latinx white adolescents. Having unmarried/unpartnered parents was associated with higher problematic social media use. Although higher household income was generally protective against problematic video game use, these associations were weaker for black than white adolescents (p for interaction <0.05).

Conclusions: Given the sociodemographic differences in problematic screen use, digital literacy education strategies can focus on at-risk populations, encourage targeted counseling by pediatricians, and adapt family media use plans for diverse backgrounds.

Impact: While sociodemographic differences in screen time are documented, we examined sociodemographic differences in problematic screen use in a large, diverse sample of early adolescents in the US. Boys reported higher problematic video game use while girls reported higher problematic social media and mobile phone use. Native American, black, and Latinx adolescents reported higher scores across all problematic screen measures compared to non-Latinx white adolescents. Although higher household income was generally protective against problematic video game use, these associations were weaker for black than white adolescents. Beyond time spent on screens, pediatricians, parents, and educators should be aware of sociodemographic differences in problematic screen use.

Family Well-Being During the COVID-19 Pandemic: The Risks of Financial Insecurity and Coping

Gonzalez MR, Brown SA, Pelham WE 3rd, Bodison SC, McCabe C, Baker FC, Baskin-Sommers A, Dick AS, Dowling GJ, Gebreselassie S, Guillaume M, Marshall AT, Sheth C, Sowell ER, Van Rinsveld A, Tapert SF. Family Well-Being During the COVID-19 Pandemic: The Risks of Financial Insecurity and Coping. J Res Adolesc. 2022 Jun 24. doi: 10.1111/jora.12776. Epub ahead of print. PMID: 35748113.

During the COVID-19 pandemic, families have experienced unprecedented financial and social disruptions. We studied the impact of preexisting psychosocial factors and pandemic-related financial and social disruptions in relation to family well-being among N = 4091 adolescents and parents during early summer 2020, participating in the Adolescent Brain Cognitive DevelopmentSM Study. Poorer family well-being was linked to prepandemic psychosocial and financial adversity and was associated with pandemic-related material hardship and social disruptions to routines. Parental alcohol use increased risk for worsening of family relationships, while a greater endorsement of coping strategies was mainly associated with overall better family well-being. Financial and mental health support may be critical for family well-being during and after a widespread crisis, such as the COVID-19 pandemic.

The Associations between Religion, Impulsivity, and Externalizing Behaviors in the Adolescent Brain Cognitive Development (ABCD) Study

Fahey KM, Nakai SC, Edwards JA, Dermody SS. The Associations between Religion, Impulsivity, and Externalizing Behaviors in the Adolescent Brain Cognitive Development (ABCD) Study. The International Journal for the Psychology of Religion, Published online: 20 Jun 2022, https://doi.org/10.1080/10508619.2022.2078590

In studies of adolescents and adults, religiosity has been identified as a protective factor for impulsivity-related behaviors and externalizing problems. No known studies to date have examined the relationship between religiosity and such outcomes in children. Thus, the current study examined in children whether (1) religion is associated with decreased impulsivity and externalizing symptoms, and if (2) religiosity is a protective factor in the association between impulsivity and externalizing symptoms. Data were from Wave 1 of the Adolescent Brain Cognitive Development (ABCD) study (children aged 9–10, N = 11,875). Two self-report measures and the Cash Choice Task assessed impulsivity; the Child Behavior Checklist assessed externalizing symptoms; and child religiosity was assessed in parent interviews. Structural equation models examined religiosity (affiliation, service attendance, importance) as a moderator between impulsivity and externalizing symptoms. Greater religious attendance was significantly associated with decreased impulsivity. Christian affiliation was associated with increased impulsivity as compared to other religions. Contrary to our hypotheses, religiosity did not moderate associations between impulsivity and externalizing symptoms. Findings suggest that impulsivity and externalizing behaviors are related to some domains of religiosity in children; however, the magnitude of the effect sizes was small, suggesting religiosity is not a particularly salient predictor of externalizing problems in children. Given these findings differ from those seen in studies of adolescents and adults, future studies should consider longitudinal designs to better understand how these relationships form across the lifespan.

Association between adverse childhood experiences and diet, exercise, and sleep in pre-adolescents

Lewis-de Los Angeles WW. Association between adverse childhood experiences and diet, exercise, and sleep in pre-adolescents. Acad Pediatr. 2022 Jun 18:S1876-2859(22)00300-X. doi: 10.1016/j.acap.2022.06.007. Epub ahead of print. PMID: 35728730.

Objective: To understand the relationship between adverse childhood experiences (ACEs) and diet, sleep, and exercise in pre-adolescents.

Methods: Baseline and one year follow-up data from the adolescent brain and cognitive development (ABCD) study were analyzed (age 10-11, n = 11,875). ACEs were measured by parent report at baseline. Three levels of ACEs were created: none, exposure to one ACE, and exposure to two or more ACEs. Health-promoting behaviors were assessed at 1-year. Diet quality was measured from parent report; sleep problems were measured by parent report, with higher scores indicating worse sleep; and amount of exercise was measured by youth report. Linear regression analyses were used to assess the relationship between ACEs and each health-promoting behavior, adjusting for family income and sex.

Results: Compared to children with no adversity, ACEs were associated with worse diet – one ACE (β=-0.30 (95% CI -0.49 to -0.12), p=0.002) and two or more ACEs (β=-0.56 (-0.78 to -0.34), p<0.001). Similarly, ACEs were associated with poor sleep – one ACE (β=1.51 (1.00 to 2.03), p<0.001) and two or more ACEs (β=2.96 (2.38 to 3.53), p<0.001). Finally, amount of exercise was not different in children with ACEs – two or more ACEs (β=-0.24, 95% CI: -0.51 to 0.04, p = 0.08).

Conclusions: ACEs in pre-adolescents show a dose-response relationship with unhealthy diet and sleep disruption. These findings suggest potential behaviors to target to mitigate the negative impact of childhood adversity on adult health.

Associations of polygenic risk for attention-deficit/hyperactivity disorder with general and specific dimensions of childhood psychological problems and facets of impulsivity

Lahey BB, Tong L, Pierce B, Hedeker D, Berman MG, Cardenas-Iniguez C, Moore TM, Applegate B, Tiemeier H, Kaczkurkin AN. Associations of polygenic risk for attention-deficit/hyperactivity disorder with general and specific dimensions of childhood psychological problems and facets of impulsivity. J Psychiatr Res. 2022 Jun 14;152:187-193. doi: 10.1016/j.jpsychires.2022.06.019. Epub ahead of print. PMID: 35752070.

A polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) has been found to be associated with ADHD in multiple studies, but also with many other dimensions of problems. Little is known, however, about the processes underlying these transdiagnostic associations. Using data from the baseline and 1-year follow-up assessments of 9- to 10-year-old children in the Adolescent Brain Cognitive Development™ (ABCD©) Study, associations were assessed between an ADHD PRS and both general and specific factors of psychological problems defined in bifactor modeling. Additionally, prospective mediated paths were tested from the ADHD PRS to dimensions of problems in the follow-up assessment through baseline measures of executive functioning (EF) and two facets of impulsivity: lower perseverance and greater impulsiveness in the presence of surgent positive emotions. Previous findings of modest but significant direct associations of the ADHD PRS with the general factor of psychological problems were replicated in both assessments in 4,483 children of European ancestry. In addition, significant statistical mediation was found from the ADHD PRS to the general factor, specific ADHD, and conduct problems in the follow-up assessment through each of the two facets of impulsivity. In contrast, EF did not statistically mediate associations between the ADHD PRS and psychological problems. These results suggest that polygenic risk transdiagnostically influences both psychological problems and facets of impulsivity, perhaps partly through indirect pathways via facets of impulsivity.

Explainable machine learning approach to predict and explain the relationship between task-based fMRI and individual differences in cognition

Pat N, Wang Y, Bartonicek A, Candia J, Stringaris A. Explainable machine learning approach to predict and explain the relationship between task-based fMRI and individual differences in cognition. Cereb Cortex. 2022 Jun 13:bhac235. doi: 10.1093/cercor/bhac235. Epub ahead of print. PMID: 35697648.

Despite decades of costly research, we still cannot accurately predict individual differences in cognition from task-based functional magnetic resonance imaging (fMRI). Moreover, aiming for methods with higher prediction is not sufficient. To understand brain-cognition relationships, we need to explain how these methods draw brain information to make the prediction. Here we applied an explainable machine-learning (ML) framework to predict cognition from task-based fMRI during the n-back working-memory task, using data from the Adolescent Brain Cognitive Development (n = 3,989). We compared 9 predictive algorithms in their ability to predict 12 cognitive abilities. We found better out-of-sample prediction from ML algorithms over the mass-univariate and ordinary least squares (OLS) multiple regression. Among ML algorithms, Elastic Net, a linear and additive algorithm, performed either similar to or better than nonlinear and interactive algorithms. We explained how these algorithms drew information, using SHapley Additive explanation, eNetXplorer, Accumulated Local Effects, and Friedman’s H-statistic. These explainers demonstrated benefits of ML over the OLS multiple regression. For example, ML provided some consistency in variable importance with a previous study and consistency with the mass-univariate approach in the directionality of brain-cognition relationships at different regions. Accordingly, our explainable-ML framework predicted cognition from task-based fMRI with boosted prediction and explainability over standard methodologies.

Estimating the Association Between Exposome and Psychosis as Well as General Psychopathology: Results From the ABCD Study

Pries LK, Moore TM, Visoki E, Sotelo I, Barzilay R, Guloksuz S. Estimating the Association Between Exposome and Psychosis as Well as General Psychopathology: Results From the ABCD Study. Biol Psychiatry Glob Open Sci. 2022 Jun 1;2(3):283-291. doi: 10.1016/j.bpsgos.2022.05.005. PMID: 36325038; PMCID: PMC9616253.

Background: The exposome comprises all nongenetic factors an individual is exposed to across their lifespan. Research suggests that exposomic vulnerability for schizophrenia is associated not only with psychosis but also, to a degree, with general psychopathology. Here, we investigated to what degree exposome factors are associated with psychosis and general psychopathology.

Methods: Data were retrieved from the 1-year follow-up assessment of a large U.S. adolescent sample (n = 11,235), the Adolescent Brain Cognitive Development (ABCD) Study. Iterative factor analyses of environmental exposures (n = 798) allowed calculation of 6 exposome factors: household adversity, neighborhood environment, day-to-day experiences, state-level environment, family values, pregnancy/birth complications. Bifactor modeling of clinical symptoms (n = 93) allowed calculation of a general psychopathology factor (p-factor) and 6 subdomains, including a psychosis subdomain. We applied linear regression analyses to estimate the association of exposome factors with the p-factor and psychosis subdomain, respectively.

Results: Individual analyses showed that 5 exposome factors were significantly associated with the p-factor after multiple-comparison correction. In the mutually adjusted model, all exposome factors were significantly associated with the p-factor. Psychosis was particularly associated with 3 exposome factors, with the mutually adjusted model yielding the following results: household adversity (β = 0.04, 95% CI, 0.01 to 0.07), day-to-day experiences (β = 0.10, 95% CI, 0.08 to 0.12), and pregnancy/birth complications (β = 0.03, 95% CI, 0.01 to 0.05).

Conclusions: Our findings demonstrate that multifaceted environmental background is associated with mental disorders. Psychosis was particularly associated with prenatal, perinatal, and childhood (household and school) adversities, although these exposome domains were also associated with psychopathology. The exposome approach can help understand neurodevelopmental psychopathology.

Associations between organized sport participation and mental health difficulties: Data from over 11,000 US children and adolescents

Hoffmann MD, Barnes JD, Tremblay MS, Guerrero MD. Associations between organized sport participation and mental health difficulties: Data from over 11,000 US children and adolescents. PLoS One. 2022 Jun 1;17(6):e0268583. doi: 10.1371/journal.pone.0268583. PMID: 35648742.

The purpose of this study was to explore the association between participation in organized sport and a broad array of mental health difficulties among US children and adolescents. The data (cross-sectional) were from Data Release 3.0 (one-year follow-up visits on the full cohort) of the Adolescent Brain Cognitive Development (ABCD) study-a broadly representative sample of 11,235 US children and adolescents aged 9 to 13 years. Parents/guardians provided self-reports of their child’s mental health difficulties using the Child Behavior Checklist. To assess participation in organized sport, children and adolescents were categorized into one of four groups: 1) participation in team sport, 2) participation in individual sport, 3) participation in team and individual sport, and 4) non-sport participation. Participation in team sport compared to non-sport participation was associated with 10% lower anxious/depressed scores, 19% lower withdrawn/depressed scores, 17% lower social problems scores, 17% lower thought problems scores, and 12% lower attention problems scores. Participation in team sport compared to non-sport participation was also associated with 20% lower rule-breaking behavior scores for females (compared to males). Conversely, participation in individual sport compared to non-sport participation was associated with 16% higher anxious/depressed scores, 14% higher withdrawn/depressed scores, 12% higher social problems scores, and 14% higher attention problems scores. Participation in both team and individual sport compared to non-sport participation was associated with 17% lower rule-breaking behavior scores for females (compared to males). Results indicate that team sport participation was associated with fewer mental health difficulties, whereas individual sport participation was associated with greater mental health difficulties. The findings complement previous research suggesting that team sport participation may be a vehicle to support child and adolescent mental health. Additional research is needed to determine to what extent, and under what circumstances, participation in individual sport may be problematic for younger cohorts.

Association of Cyberbullying Experiences and Perpetration With Suicidality in Early Adolescence

Arnon S, Brunstein Klomek A, Visoki E, Moore TM, Argabright ST, DiDomenico GE, Benton TD, Barzilay R. Association of Cyberbullying Experiences and Perpetration With Suicidality in Early Adolescence. JAMA Netw Open. 2022 Jun 1;5(6):e2218746. doi: 10.1001/jamanetworkopen.2022.18746. PMID: 35759263.

Importance: Adolescent suicidality (ie, suicidal ideation or attempts) is a major public health concern. Cyberbullying experiences and perpetration have become increasingly prevalent and are associated with mental health burden, but their roles as independent suicidality risk factors remain unclear. Data are needed to clarify their contribution to teen suicidality to inform suicide prevention efforts.

Objective: To examine whether cyberbullying experiences and perpetration are distinct stressors divergent from other forms of peer aggression experiences in their association with suicidality in early adolescence.

Design, setting, and participants: This cross-sectional analysis used data collected between July 2018 and January 2021 from the Adolescent Brain Cognitive Development (ABCD) study, a large, diverse sample of US children aged 10 to 13 years.

Exposures: Youth reports of cyberbullying experiences or perpetration.

Main outcomes and measures: The main outcome was youth-reported suicidality (past or present, as reported in the ABCD 2-year follow-up assessment). Covariates included demographics, established environmental risk and protective factors for youth suicidality, psychopathology, and experiences or perpetration of offline peer aggression.

Results: A total of 10 414 ABCD participants were included in this study. Participants had a mean (SD) age of 12.0 (0.7) years and 4962 (47.6%) were female; 796 (7.6%) endorsed suicidality. A total of 930 (8.9%) reported experiencing cyberbullying and 96 (0.9%) reported perpetrating cyberbullying. Of the perpetrators, 66 (69.0%) also endorsed experiencing cyberbullying. Controlling for demographics, experiencing cyberbullying was associated with suicidality (odds ratio [OR], 4.2 [95% CI, 3.5-5.1]; P < .001), whereas perpetrating cyberbullying was not (OR, 1.3 [95% CI, 0.8-2.3]; P = .30). Experiencing cyberbullying remained associated with suicidality when accounting for negative life events, family conflict, parental monitoring, school environment, and racial and ethnic discrimination (OR, 2.5 [95% CI, 2.0-3.0]; P < .001) and when further covarying for internalizing and externalizing psychopathology (OR, 1.8 [95% CI, 1.4-2.4]; P < .001). Both being a target and being a perpetrator of offline peer aggression were associated with suicidality (OR, 1.5 [95% CI, 1.1-2.0] for both), controlling for all covariates described earlier. Cyberbullying experiences remained associated with suicidality (OR, 1.7 [95% CI, 1.3-2.2]; P < .001, controlling for all covariates) when included with offline peer aggression experiences and perpetration.

Conclusions and relevance: In this cross-sectional study, experiencing-but not perpetrating-cyberbullying was associated with suicidality in early adolescence. This association was significant over and above other suicidality risk factors, including offline peer aggression experiences or perpetration. These findings can inform adolescent suicide prevention strategies, and they suggest that clinicians and educational staff working with this population should routinely evaluate for adolescents’ experience with cyberbullying.

 

The Mediating Role of Family Acceptance and Conflict on Suicidality among Sexual and Gender Minority Youth

Klein DA, Ahmed AE, Murphy MA, Pearlman AT, Johnson N, Gray JC, Schvey NA. The Mediating Role of Family Acceptance and Conflict on Suicidality among Sexual and Gender Minority Youth. Arch Suicide Res. 2022 May 24:1-8. doi: 10.1080/13811118.2022.2075815. Epub ahead of print. PMID: 35608364.

Introduction: Prior research suggests sexual and gender minority (SGM) youth are profoundly impacted by levels of parental support. This study assessed mediating effects of generalized family acceptance and conflict on lifetime suicidal behaviors among a large diverse sample comprising both SGM and non-SGM youth in early adolescence, when intervention to optimize family dynamics may be critical.

Materials: Using data from the first-year follow-up of the Adolescent Brain Cognitive Development Study based in the United States, mediation was tested using a binary logistic regression model fitted with a generalized structural equation. Models included SGM status as the independent variable, family acceptance or family conflict sum score as the mediator, and the presence of lifetime suicidal behaviors as the dependent variable. Models adjusted for age, birth-assigned sex (as reported by the parent/guardian), and race/ethnicity.

Results: Of 11,235 youths, lifetime suicidal behaviors were reported by 1.5% (n = 164). Youths with SGM identities reported 40% less parental acceptance and 47% greater family conflict, compared to non-SGM peers. Both parental acceptance and family conflict partially mediated associations between SGM identification and odds of lifetime suicidal behavior (ps = .001).

Conclusions: Identification of modifiable risk factors for suicidality in this vulnerable population, including parental acceptance and family conflict, is critical to improving health outcomes. Clinicians should work with SGM youth and their families starting in childhood to optimize family dynamics and bolster acceptance to potentially reduce adverse health outcomes.

HIGHLIGHTS Youths with SGM identity reported 40% less parental acceptance than non-SGM peers. Parental acceptance was associated with lower odds of lifetime suicidal behaviors. Family factors partially mediated associations between SGM status and suicidal behaviors.

Anxiety, depression, and substance experimentation in childhood

Klein RJ, Gyorda JA, Jacobson NC. Anxiety, depression, and substance experimentation in childhood. PLoS One. 2022 May 24;17(5):e0265239. doi: 10.1371/journal.pone.0265239. PMID: 35609016.

Previous research has demonstrated that adults with comorbid depressive and anxiety disorders are significantly more likely to show pathological use of drugs or alcohol. Few studies, however, have examined associations of this type in children. A better understanding of the relationships between affective disorders and substance experimentation in childhood could help clarify the complex ways in which pathological substance use symptoms develop early in life. The present study included 11,785 children (Mage = 9.9) participating in the Adolescent Brain Cognitive Development (ABCD) study. Depressive and anxiety disorder diagnoses were evaluated as concurrent predictors of experimentation with alcohol and tobacco. A series of linear regressions revealed that children with either depressive or anxiety disorders were significantly more likely to experiment with alcohol or tobacco. However, children with both depressive and anxiety diagnoses were not more likely to experiment than children without a diagnosis. These results suggest that anxiety or depressive diagnoses in childhood may be associated with a greater likelihood of substance experimentation, but severe psychological distress may suppress these effects.

Relationship Between Neighborhood Poverty and Externalizing Symptoms in Children: Mediation and Moderation by Environmental Factors and Brain Structure

Maxwell MY, Taylor RL, Barch DM. Relationship Between Neighborhood Poverty and Externalizing Symptoms in Children: Mediation and Moderation by Environmental Factors and Brain Structure. Child Psychiatry Hum Dev. 2022 May 21. doi: 10.1007/s10578-022-01369-w. Epub ahead of print. PMID: 35596841.

Children living in poverty exhibit worse mental health outcomes, and various environmental and neurological risk factors may contribute to or mitigate this relationship. However, previous research has not examined the interplay of neighborhood SES, mental health, and relevant mechanisms. We examined the extent to which neighborhood poverty uniquely contributes to children’s internalizing/externalizing disorder symptoms, as well as identified whether brain measures, toxin levels, and neighborhood threat mediated this relationship and whether socioemotional support moderated it. Data were collected from 8623 9-10 year olds as part of the Adolescent Brain Cognitive Development study. Using a secondary data analysis, we found that neighborhood poverty was positively associated with externalizing symptoms and mediated by reduced intracranial volume and parents/children reporting feeling less safe. Parental support (i.e., Parental Monitoring Survey) attenuated this link, but only for children lower in poverty. Consideration of these risk factors for psychopathology could improve the outcome of holistic interventions.

A practical guide for researchers and reviewers using the ABCD Study and other large longitudinal datasets

Saragosa-Harris NM, Chaku N, MacSweeney N, Guazzelli Williamson V, Scheuplein M, Feola B, Cardenas-Iniguez C, Demir-Lira E, McNeilly EA, Huffman LG, Whitmore L, Michalska KJ, Damme KS, Rakesh D, Mills KL. A practical guide for researchers and reviewers using the ABCD Study and other large longitudinal datasets. Dev Cogn Neurosci. 2022 May 20;55:101115. doi: 10.1016/j.dcn.2022.101115. Epub ahead of print. PMID: 35636343; PMCID: PMC9156875.

As the largest longitudinal study of adolescent brain development and behavior to date, the Adolescent Brain Cognitive Development (ABCD) Study® has provided immense opportunities for researchers across disciplines since its first data release in 2018. The size and scope of the study also present a number of hurdles, which range from becoming familiar with the study design and data structure to employing rigorous and reproducible analyses. The current paper is intended as a guide for researchers and reviewers working with ABCD data, highlighting the features of the data (and the strengths and limitations therein) as well as relevant analytical and methodological considerations. Additionally, we explore justice, equity, diversity, and inclusion efforts as they pertain to the ABCD Study and other large-scale datasets. In doing so, we hope to increase both accessibility of the ABCD Study and transparency within the field of developmental cognitive neuroscience.

Multi-tract multi-symptom relationships in pediatric concussion

Guido I Guberman, Sonja Stojanovski, Eman Nishat, Alain Ptito, Danilo Bzdok, Anne L Wheeler, Maxime Descoteaux (2022). Multi-tract multi-symptom relationships in pediatric concussion. eLife 11:e70450, https://doi.org/10.7554/eLife.70450

Background: The heterogeneity of white matter damage and symptoms in concussion has been identified as a major obstacle to therapeutic innovation. In contrast, most diffusion MRI (dMRI) studies on concussion have traditionally relied on group-comparison approaches that average out heterogeneity. To leverage, rather than average out, concussion heterogeneity, we combined dMRI and multivariate statistics to characterize multi-tract multi-symptom relationships.

Methods: Using cross-sectional data from 306 previously-concussed children aged 9-10 from the Adolescent Brain Cognitive Development Study, we built connectomes weighted by classical and emerging diffusion measures. These measures were combined into two informative indices, the first representing microstructural complexity, the second representing axonal density. We deployed pattern-learning algorithms to jointly decompose these connectivity features and 19 symptom measures.

Results: Early multi-tract multi-symptom pairs explained the most covariance and represented broad symptom categories, such as a general problems pair, or a pair representing all cognitive symptoms, and implicated more distributed networks of white matter tracts. Further pairs represented more specific symptom combinations, such as a pair representing attention problems exclusively, and were associated with more localized white matter abnormalities. Symptom representation was not systematically related to tract representation across pairs. Sleep problems were implicated across most pairs, but were related to different connections across these pairs. Expression of multi-tract features was not driven by sociodemographic and injury-related variables, as well as by clinical subgroups defined by the presence of ADHD. Analyses performed on a replication dataset showed consistent results.

Conclusions: Using a double-multivariate approach, we identified clinically-informative, cross-demographic multi-tract multi-symptom relationships. These results suggest that rather than clear one-to-one symptom-connectivity disturbances, concussions may be characterized by subtypes of symptom/connectivity relationships. The symptom/connectivity relationships identified in multi-tract multi-symptom pairs were not apparent in single-tract/single-symptom analyses. Future studies aiming to better understand connectivity/symptom relationships should take into account multi-tract multi-symptom heterogeneity.

Limits to the generalizability of resting-state functional magnetic resonance imaging studies of youth: An examination of ABCD Study® baseline data

Cosgrove, K.T., McDermott, T.J., White, E.J. et al. Limits to the generalizability of resting-state functional magnetic resonance imaging studies of youth: An examination of ABCD Study® baseline data. Brain Imaging and Behavior (2022). https://doi.org/10.1007/s11682-022-00665-2

This study examined how resting-state functional magnetic resonance imaging (rs-fMRI) data quality and availability relate to clinical and sociodemographic variables within the Adolescent Brain Cognitive Development Study. A sample of participants with an adequate sample of quality baseline rs-fMRI data containing low average motion (framewise displacement ≤ 0.15; low-noise; n = 4,356) was compared to a sample of participants without an adequate sample of quality data and/or containing high average motion (higher-noise; n = 7,437) using Chi-squared analyses and t-tests. A linear mixed model examined relationships between clinical and sociodemographic characteristics and average head motion in the sample with low-noise data. Relative to the sample with higher-noise data, the low-noise sample included more females, youth identified by parents as non-Hispanic white, and youth with married parents, higher parent education, and greater household incomes (ORs = 1.32–1.42). Youth in the low-noise sample were also older and had higher neurocognitive skills, lower BMIs, and fewer externalizing and neurodevelopmental problems (ds = 0.12–0.30). Within the low-noise sample, several clinical and demographic characteristics related to motion. Thus, participants with low-noise rs-fMRI data may be less representative of the general population and motion may remain a confound in this sample. Future rs-fMRI studies of youth should consider these limitations in the design and analysis stages in order to optimize the representativeness and clinical relevance of analyses and results.

The impact of digital media on children’s intelligence while controlling for genetic differences in cognition and socioeconomic background

Sauce, B., Liebherr, M., Judd, N. et al. The impact of digital media on children’s intelligence while controlling for genetic differences in cognition and socioeconomic background. Sci Rep 12, 7720 (2022). https://doi.org/10.1038/s41598-022-11341-2

Digital media defines modern childhood, but its cognitive effects are unclear and hotly debated. We believe that studies with genetic data could clarify causal claims and correct for the typically unaccounted role of genetic predispositions. Here, we estimated the impact of different types of screen time (watching, socializing, or gaming) on children’s intelligence while controlling for the confounding effects of genetic differences in cognition and socioeconomic status. We analyzed 9855 children from the USA who were part of the ABCD dataset with measures of intelligence at baseline (ages 9–10) and after two years. At baseline, time watching (r = − 0.12) and socializing (r = − 0.10) were negatively correlated with intelligence, while gaming did not correlate. After two years, gaming positively impacted intelligence (standardized β =  + 0.17), but socializing had no effect. This is consistent with cognitive benefits documented in experimental studies on video gaming. Unexpectedly, watching videos also benefited intelligence (standardized β =  + 0.12), contrary to prior research on the effect of watching TV. Although, in a posthoc analysis, this was not significant if parental education (instead of SES) was controlled for. Broadly, our results are in line with research on the malleability of cognitive abilities from environmental factors, such as cognitive training and the Flynn effect.

Prediction of the trajectories of depressive symptoms among children in the adolescent brain cognitive development (ABCD) study using machine learning approach

Xiang Q, Chen K, Peng L, Luo J, Jiang J, Chen Y, Lan L, Song H, Zhou X. Prediction of the trajectories of depressive symptoms among children in the adolescent brain cognitive development (ABCD) study using machine learning approach. J Affect Disord. 2022 May 8:S0165-0327(22)00523-7. doi: 10.1016/j.jad.2022.05.020. Epub ahead of print. PMID: 35545159.

Background: Depression often first emerges during adolescence and evidence shows that the long-term patterns of depressive symptoms over time are heterogeneous. It is meaningful to predict the trajectory of depressive symptoms in adolescents to find early intervention targets.

Methods: Based on the Adolescent Brain Cognitive Development Study, we included 4962 participants aged 9-10 who were followed-up for 2 years. Trajectories of depressive symptoms were identified by Latent Class Growth Analyses (LCGA). Four types of machine learning models were built to predict the identified trajectories and to obtain variables with predictive value based on the best performance model.

Results: Of all participants, 536 (10.80%) were classified as increasing, 269 (5.42%) as persistently high, 433 (8.73%) as decreasing, and 3724 (75.05%) as persistently low by LCGA. Gradient Boosting Machine (GBM) model got the highest discriminant performance. Sleep quality, parental emotional state and family financial adversities were the most important predictors and three resting state functional magnetic resonance imaging functional connectivity data were also helpful to distinguish trajectories.

Limitation: We only have depressive symptom scores at three time points. Some valuable predictors are not specific to depression. External validation is an important next step. These predictors should not be interpreted as etiology and some variables were reported by parents/caregivers.

Conclusion: Using GBM combined with baseline characteristics, the trajectories of depressive symptoms with two years among adolescents aged 9-10 years can be well predicted, which might further facilitate the identification of adolescents at high risk of depressive symptoms and development of effective early interventions.

Parent-Child Concordance and Discordance in Family Violence Reporting: A Descriptive Analysis from the Adolescent Brain Cognitive Development Study®

Hogan JN, Garcia AM, Tomko RL, Squeglia LM, Flanagan JC. Parent-Child Concordance and Discordance in Family Violence Reporting: A Descriptive Analysis from the Adolescent Brain Cognitive Development Study®. J Interpers Violence. 2022 May 7:8862605221081928. doi: 10.1177/08862605221081928. Epub ahead of print. PMID: 35531607.

Childhood trauma exposure, including witnessing or experiencing family violence, is associated with a variety of poor outcomes such as increased likelihood of psychopathology and high-risk behaviors across the lifespan. Early treatment may help to buffer these effects, but parents and youth display only moderate levels of agreement in reporting family violence, making it more difficult to identify children who have been exposed. Additionally, most studies on family violence reporting have focused primarily on small samples in specific high-risk populations, and little is known about the generalizability of these findings. Thus, the present study assessed concordance in family violence reporting and its correlates using the population-based, demographically diverse sample from the U.S. Adolescent Brain Cognitive Development (ABCD®) study. Participants were 10,532 children between 9 and 10 years old, and their parent or guardian, from 21 sites across the United States. Overall, 30% (N = 3119) of the sample reported family violence and most of those reports (N = 2629) had discordant violence reporting, meaning child- and parent-report did not correspond with each other. Multinomial logistic regression was used to assess the likelihood of participants belonging in one of the following groups: no violence reported, concordant violence reported, and discordant violence reported. Results indicated that Black or Non-Hispanic children, male children, and children with greater externalizing problems were more likely to report family violence, and parents with lower levels of education and income were more likely to report family violence. These findings likely reflect differences in distribution of risk factors among racial and ethnic minoritized individuals including increased parenting stress and decreased access to mental health treatment. Among those reporting violence, Hispanic children and children with less externalizing problems were more likely to be in the discordant group. Findings suggest that both parent and child reports are needed to assess violence and screen for appropriate services.

T1w/T2w Ratio and Cognition in 9-to-11-Year-Old Children

Langansee L, Rumetshofer T, Behjat H, Novén , Li P, Mårtensson J. T1w/T2w Ratio and Cognition in 9-to-11-Year-Old Children. Brain Sci. 2022, 12(5), 599; https://doi.org/10.3390/brainsci12050599

Childhood is a period of extensive cortical and neural development. Among other things, axons in the brain gradually become more myelinated, promoting the propagation of electrical signals between different parts of the brain, which in turn may facilitate skill development. Myelin is difficult to assess in vivo, and measurement techniques are only just beginning to make their way into standard imaging protocols in human cognitive neuroscience. An approach that has been proposed as an indirect measure of cortical myelin is the T1w/T2w ratio, a contrast that is based on the intensities of two standard structural magnetic resonance images. Although not initially intended as such, researchers have recently started to use the T1w/T2w contrast for between-subject comparisons of cortical data with various behavioral and cognitive indices. As a complement to these earlier findings, we computed individual cortical T1w/T2w maps using data from the Adolescent Brain Cognitive Development study (N = 960; 449 females; aged 8.9 to 11.0 years) and related the T1w/T2w maps to indices of cognitive ability; in contrast to previous work, we did not find significant relationships between T1w/T2w values and cognitive performance after correcting for multiple testing. These findings reinforce existent skepticism about the applicability of T1w/T2w ratio for inter-individual comparisons.

Multivariate genome-wide association study on tissue-sensitive diffusion metrics highlights pathways that shape the human brain

Fan CC, Loughnan R, Makowski C, Pecheva D, Chen CH, Hagler DJ Jr, Thompson WK, Parker N, van der Meer D, Frei O, Andreassen OA, Dale AM. Multivariate genome-wide association study on tissue-sensitive diffusion metrics highlights pathways that shape the human brain. Nat Commun. 2022 May 3;13(1):2423. doi: 10.1038/s41467-022-30110-3. PMID: 35505052.

The molecular determinants of tissue composition of the human brain remain largely unknown. Recent genome-wide association studies (GWAS) on this topic have had limited success due to methodological constraints. Here, we apply advanced whole-brain analyses on multi-shell diffusion imaging data and multivariate GWAS to two large scale imaging genetic datasets (UK Biobank and the Adolescent Brain Cognitive Development study) to identify and validate genetic association signals. We discover 503 unique genetic loci that have impact on multiple regions of human brain. Among them, more than 79% are validated in either of two large-scale independent imaging datasets. Key molecular pathways involved in axonal growth, astrocyte-mediated neuroinflammation, and synaptogenesis during development are found to significantly impact the measured variations in tissue-specific imaging features. Our results shed new light on the biological determinants of brain tissue composition and their potential overlap with the genetic basis of neuropsychiatric disorders.

Nucleus Accumbens Fractional Anisotropy and Children’s Body Mass Index: Moderating Role of Race and Family Income

Assari S. (2022). Nucleus Accumbens Fractional Anisotropy and Children’s Body Mass Index: Moderating Role of Race and Family Income. International Journal of Epidemiologic Research, Volume 9, Issue 2 – Serial Number 31, May 2022, Pages 54-60.

Background and aims: The nucleus accumbens (NAcc) functional and morphometric features may influence children’s body mass index (BMI). Recent evidence, however, suggests that the function and structure of the NAcc may have different predictive abilities for the BMI for the sub-groups of children from different racial and socioeconomic status (SES) backgrounds. Using the Adolescent Brain Cognitive Development data, this study investigated racial and SES differences in the association between NAcc microstructure (i.e., fractional anisotropy) and childhood BMI.

Methods: This cross-sectional study included 9497 children aged 9 and 10. Data were collected from 21 sites across 15 states in the United States. Then, the mixed-effects regression model was applied for data analysis. The predictor variable of interest was NAcc fractional anisotropy measured using diffusion magnetic resonance imaging (dMRI). The main outcome of interest was children’s BMI values, which were treated as a continuous variable. Covariates included gender, age, and family structure. Race (White, Black, Asian, and Other/mixed) and family income ( < USD 50,000, USD 50,000-100,000, and USD100,000+) were the effect modifiers (moderators).

Results: Higher average NAcc fractional anisotropy in dMRI was predictive of lower levels of the BMI, and net of covariates. However, this inverse association between the average intensity of the normalized T2-weighted image and the BMI was stronger in children from Hispanic, low income, and low-educated backgrounds compared to non-Hispanic, high-income, and high-educated backgrounds.

Conclusion: Our findings suggested that although NAcc fractional anisotropy is linked to children’s BMI, this link is not invariant across racial and SES groups. The issue of whether or not obesogenic environments alter the implications of NAcc for childhood BMI needs further investigation. For diverse groups, NAcc microstructures may have different magnitudes of associations with childhood BMI.

Longer screen time utilization is associated with the polygenic risk for Attention-deficit/hyperactivity disorder with mediation by brain white matter microstructure

Yang A, Rolls ET, Dong G, Du J, Li Y, Feng J, Cheng W, Zhao XM. Longer screen time utilization is associated with the polygenic risk for Attention-deficit/hyperactivity disorder with mediation by brain white matter microstructure. EBioMedicine. 2022 May 1;80:104039. doi: 10.1016/j.ebiom.2022.104039. Epub ahead of print. PMID: 35509143.

Background: Attention-deficit/hyperactivity disorder (ADHD) has been reported to be associated with longer screen time utilization (STU) at the behavioral level. However, whether there are shared neural links between ADHD symptoms and prolonged STU is not clear and has not been explored in a single large-scale dataset.

Methods: Leveraging the genetics, neuroimaging and behavioral data of 11,000+ children aged 9-11 from the Adolescent Brain Cognitive Development cohort, this study investigates the associations between the polygenic risk and trait for ADHD, STU, and white matter microstructure through cross-sectionally and longitudinal analyses.

Findings: Children with higher polygenic risk scores for ADHD tend to have longer STU and more severe ADHD symptoms. Fractional anisotropy (FA) values in several white matter tracts are negatively correlated with both the ADHD polygenic risk score and STU, including the inferior frontal-striatal tract, inferior frontal-occipital fasciculus, superior longitudinal fasciculus and corpus callosum. Most of these tracts are linked to visual-related functions. Longitudinal analyses indicate a directional effect of white matter microstructure on the ADHD scale, and a bi-directional effect between the ADHD scale and STU. Furthermore, reduction of FA in several white matter tracts mediates the association between the ADHD polygenic risk score and STU.

Interpretation: These findings shed new light on the shared neural overlaps between ADHD symptoms and prolonged STU, and provide evidence that the polygenic risk for ADHD is related, via white matter microstructure and the ADHD trait, to STU.

Cyberbullying involvement and short sleep duration among adolescents

Sampasa-Kanyinga H, Lien A, Hamilton HA, Chaput JP. Cyberbullying involvement and short sleep duration among adolescents. Sleep Health. 2022 Apr;8(2):183-190. doi: 10.1016/j.sleh.2021.11.009. Epub 2022 Feb 1. PMID: 35120851.

Background: Research has shown that cyberbullying victimization is associated with short sleep duration among adolescents; however, the association between cyberbullying perpetration and sleep duration is unclear. Furthermore, little is known about the factors that could moderate these associations. Thus, the objectives of this study were to investigate the associations of cyberbullying victimization, perpetration, or both with short sleep duration among adolescents, and to test whether age, sex, and adherence to the screen time recommendations (≤2 hours/day) moderate these associations.

Methods: Data on 6834 adolescents aged 11-20 years were derived from a representative cross-sectional study of middle and high school students across Ontario, Canada. Short sleep duration was self-reported and defined as sleeping less than the age-appropriate sleep duration recommendations. Multivariable logistic regression models were adjusted for important covariates. Adjusted odds ratios (AOR) and their 95% confidence intervals (CI) are reported.

Results: Cyberbullying victimization (AOR = 1.60, 95% CI = 1.37-1.86), perpetration (AOR = 1.44, 95% CI = 1.16-1.79), or both perpetration and victimization (AOR = 1.71, 95% CI = 1.27-2.30) was associated with greater odds of short sleep duration. Results further indicated that younger students who were not cyberbullied had a lower probability of short sleep duration, but there was no difference in the probability of short sleep duration between being cyberbullied or not among older adolescents. Sex and screen time did not moderate any of the associations between cyberbullying involvement and short sleep duration.

Conclusion: Involvement in cyberbullying as either a victim, a perpetrator, or both is associated with short sleep duration among adolescents. Strategies that can help to eliminate cyberbullying are needed in public health.

Association of Social Determinants of Health and Vaccinations With Child Mental Health During the COVID-19 Pandemic in the US

Xiao Y, Yip P S-F, Pathak J, Mann J. Association of Social Determinants of Health and Vaccinations With Child Mental Health During the COVID-19 Pandemic in the US. JAMA Psychiatry. Published online April 27, 2022. doi:10.1001/jamapsychiatry.2022.0818

Importance
The COVID-19 pandemic disproportionately affected mental health in socioeconomically disadvantaged children in the US. However, little is known about the relationship of preexisting and time-varying social determinants of health (SDoH) at individual and structural levels, vaccination eligibility/rates, and the racial and ethnic differences to trajectories of child mental health during the COVID-19 pandemic.

Objective
To estimate the association of trajectories of child mental health to multilevel SDoH and vaccination eligibility/rates.

Design, Setting, and Participants
This prospective longitudinal cohort study, conducted from May 16, 2020, to March 2, 2021, integrated structural-level, pandemic-related data with the Adolescent Brain Cognitive Development (ABCD) cohort data (release 4.0). The ABCD study recruited 11 878 children (baseline) and conducted 6 COVID-19 rapid response surveys across 21 US sites (in 17 states) from May 16, 2020, to March 2, 2021.

Exposures
Preexisting individual (eg, household income) and structural (area deprivation) SDoH and time-varying individual (eg, food insecurity, unemployment) and structural (eg, social distancing, vaccination eligibility/rates) SDoH.

Main Outcomes and Measures
Perceived Stress Scale, the National Institutes of Health–Toolbox emotion measures, and COVID-19–related worry.

Results
The longitudinal sample included 8493 children (mean [SD] age, 9.93 [0.63] years; 5011 girls [47.89%]; 245 Asian [2.34%], 1213 Black [11.59%], 2029 Hispanic [19.39%], 5851 White [55.93%], and 1124 children of other/multiracial ethnicity [10.74%]). Trajectories of stress, sadness, and COVID-19–related worry decreased after adult vaccination rollout. Compared with younger children, boys, White children, or those living with married parents, those who reported greater perceived stress included older children aged 12 to 15 years (β = 0.26; 95% CI, 0.12-0.41; P < .001); girls (β = 0.75; 95% CI, 0.61-0.89; P < .001); Hispanic children (β = 0.24; 95% CI, 0.01-0.47; P = .04); children living with separated parents (β = 0.50; 95% CI, 0.03-0.96; P = .04); children experiencing disrupted medical health care access (β = 0.19; 95% CI, 0.01-0.36; P = .04); children living in economically deprived neighborhoods (β = 0.28; 95% CI, 0.05-0.51; P = .02); children living in areas with more full-time working-class adults who were unable to social distance (β = 1.35; 95% CI, 0.13-2.67; P = .04); and children living in states with fewer fully vaccinated adults (β = 0.59; 95% CI, 0.16-1.02; P = .007). COVID-19 pandemic–related worry was higher among Asian children (β = 0.22; 95% CI, 0.08-0.37; P = .003), Black children (β = 0.33; 95% CI, 0.22-0.43; P < .001), children of other/multiracial ethnicity (β = 0.17; 95% CI, 0.09-0.25; P < .001), and children with disrupted medical health care (β = 0.15; 95% CI, 0.09-0.21) and disrupted mental health treatment (β = 0.11; 95% CI, 0.06-0.16). Inability to afford food was associated with increased sadness (β = 1.50; 95% CI, 0.06-2.93; P = .04). States with later vaccination eligibility dates for all adults were associated with greater COVID-19–related worry (β = 0.16; 95% CI, 0.01-0.31; P = .03) and decreased positive affect (β = −1.78; 95% CI, −3.39 to −0.18; P = .03) among children.

Conclusions and Relevance
Results of this study suggest a disproportionately adverse association of the COVID-19 pandemic with child mental health among racial and ethnic minority groups, which may be improved by addressing modifiable individual (food insecurity, unemployment, health services, parental supervision) and structural (area deprivation, job protection, vaccination) SDoH.

The sexual brain, genes, and cognition: A machine-predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children

Kim K, Joo YY, Ahn G, Wang HH, Moon SY, Kim H, Ahn WY, Cha J. The sexual brain, genes, and cognition: A machine-predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children. Hum Brain Mapp. 2022 Apr 26. doi: 10.1002/hbm.25888. Epub ahead of print. PMID: 35471639.

Sex impacts the development of the brain and cognition differently across individuals. However, the literature on brain sex dimorphism in humans is mixed. We aim to investigate the biological underpinnings of the individual variability of sexual dimorphism in the brain and its impact on cognitive performance. To this end, we tested whether the individual difference in brain sex would be linked to that in cognitive performance that is influenced by genetic factors in prepubertal children (N = 9,658, ages 9-10 years old; the Adolescent Brain Cognitive Development study). To capture the interindividual variability of the brain, we estimated the probability of being male or female based on the brain morphometry and connectivity features using machine learning (herein called a brain sex score). The models accurately classified the biological sex with a test ROC-AUC of 93.32%. As a result, a greater brain sex score correlated significantly with greater intelligence and higher cognitive genome-wide polygenic scores (GPSs). Structural equation models revealed that the GPS-intelligence association was significantly modulated by the brain sex score, such that a brain with a higher maleness score (or a lower femaleness score) mediated a positive GPS effect on intelligence (indirect effects = .006-.009; p = .002-.022; sex-stratified analysis). The finding of the sex modulatory effect on the gene-brain-cognition relationship presents a likely biological pathway to the individual and sex differences in the brain and cognitive performance in preadolescence.

Shared and unique brain network features predict cognitive, personality, and mental health scores in the ABCD study

Chen J, Tam A, Kebets V, Orban C, Ooi LQR, Asplund CL, Marek S, Dosenbach NUF, Eickhoff SB, Bzdok D, Holmes AJ, Yeo BTT. Shared and unique brain network features predict cognitive, personality, and mental health scores in the ABCD study. Nat Commun. 2022 Apr 25;13(1):2217. doi: 10.1038/s41467-022-29766-8. PMID: 35468875.

How individual differences in brain network organization track behavioral variability is a fundamental question in systems neuroscience. Recent work suggests that resting-state and task-state functional connectivity can predict specific traits at the individual level. However, most studies focus on single behavioral traits, thus not capturing broader relationships across behaviors. In a large sample of 1858 typically developing children from the Adolescent Brain Cognitive Development (ABCD) study, we show that predictive network features are distinct across the domains of cognitive performance, personality scores and mental health assessments. On the other hand, traits within each behavioral domain are predicted by similar network features. Predictive network features and models generalize to other behavioral measures within the same behavioral domain. Although tasks are known to modulate the functional connectome, predictive network features are similar between resting and task states. Overall, our findings reveal shared brain network features that account for individual variation within broad domains of behavior in childhood.

Effects of the physical and social environment on youth cognitive performance

Meredith WJ, Cardenas-Iniguez C, Berman MG, Rosenberg MD. Effects of the physical and social environment on youth cognitive performance. Dev Psychobiol. 2022 May;64(4):e22258. doi: 10.1002/dev.22258. PMID: 35452534.

Individual differences in children’s cognitive abilities impact life and health outcomes. What factors influence these individual differences during development? Here, we test whether children’s environments predict cognitive performance, independent of well-characterized socioeconomic effects. We analyzed data from 9002 9- to 10-year olds from the Adolescent Brain Cognitive Development Study, an ongoing longitudinal study with community samples across the United States. Using youth- and caregiver-report questionnaires and national database registries (e.g., neighborhood crime, walkability), we defined principal components summarizing children’s home, school, neighborhood, and cultural environments. In two independent samples (ns = 3475, 5527), environmental components explained unique variance in children’s general cognitive ability, executive functioning, and learning/memory abilities. Furthermore, increased neighborhood enrichment was associated with an attenuated relationship between sociodemographics and general cognitive abilities. Thus, the environment accounts for unique variance in cognitive performance in children and should be considered alongside sociodemographic factors to better understand brain functioning and behavior across development.

Internalizing Symptoms & Adverse Childhood Experiences Associated with Functional Connectivity in A Middle Childhood Sample

Albertina EA, Barch DM, Karcher NR. Internalizing Symptoms & Adverse Childhood Experiences Associated with Functional Connectivity in A Middle Childhood Sample. Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Apr 25:S2451-9022(22)00094-5. doi: 10.1016/j.bpsc.2022.04.001. Epub ahead of print. PMID: 35483606

Introduction: Research has found overlapping associations in adults of resting state functional connectivity (RSFC) to both internalizing disorders (e.g., depression, anxiety) as well as a history of traumatic events. The present study aimed to extend this previous research to a younger sample by examining RSFC associations with both internalizing symptoms and adverse childhood experiences (ACEs) in middle childhood.

Method: We used generalized linear mixed models to examine associations between a priori within- and between-network RSFC with child-reported internalizing symptoms and ACEs using the Adolescent Brain Cognitive Development dataset (N= 10,168, Mage(years)= 9.95, SDage(years)= 0.627).

Results: We found that internalizing symptoms and ACEs were associated with both multiple overlapping and unique RSFC network patterns. Both ACEs and internalizing symptoms were associated with a reduced anticorrelation between the default mode network and the dorsal attention network. However, internalizing symptoms were uniquely associated with lower within-network default mode network connectivity while ACEs were uniquely associated with both lower between-network connectivity of the auditory network and cingulo-opercular network, and higher within-network frontoparietal network connectivity.

Conclusions: The present study points to overlap in the RSFC associations with internalizing symptoms and ACEs, as well as important areas of specificity in RSFC associations. Many of the RSFC associations found have been previously implicated in attentional control functions, including modulation of attention to sensory stimuli. This may have critical importance in understanding internalizing symptoms and outcomes of ACEs.

Individual-, peer-, and parent-level substance use-related factors among 9- and 10-year-olds from the ABCD Study: Prevalence rates and sociodemographic differences

Martz ME, Heitzeg MM, Lisdahl KM, Cloak CC, Feldstein Ewing SW, Gonzalez R, Haist F, LeBlanc KH, Madden PA, Ross JM, Sher KJ, Tapert SF, Thompson WK, Wade NE. Individual-, peer-, and parent-level substance use-related factors among 9- and 10-year-olds from the ABCD Study: Prevalence rates and sociodemographic differences. Drug and Alcohol Dependence Reports. Volume 3, June 2022, 100037. https://doi.org/10.1016/j.dadr.2022.100037

Background
Although a relatively large body of research has identified multiple factors associated with adolescent substance use, less is known about earlier substance-related factors during preadolescence, including curiosity to use substances. The present study examined individual-, peer-, and parent-level domains pertaining to substance use and how these domains vary by sociodemographic subgroups and substance type.

Methods
Participants were 11,864 9- and 10-year-olds from the baseline sample of the Adolescent Brain Cognitive Development (ABCD) Study. Youth-reported measures were curiosity to use substances and perceived peer substance use. Parent-reported measures were availability of and rules about substances. Generalized logistic mixed models (GLMM) were used to compare these measures across alcohol, nicotine, and marijuana and across sociodemographic subgroupings (sex, race/ethnicity, household income, and family history of alcohol problems). GLMM was then used to examine predictors of curiosity to use by substance type.

Results
The most striking descriptive differences were found between race/ethnicity and income categories (e.g., positive associations between greater income and greater availability of alcohol). In multivariable analyses, greater curiosity to use alcohol was associated with being male, higher household income, perceived peer alcohol use, and easy alcohol availability; greater curiosity to use nicotine was associated with being male, perceived peer cigarette use, easy availability of cigarettes, and no parental rules about cigarette use.

Conclusions
This study identified substance use-related individual-, peer-, and parent-level factors among a diverse, national sample. Findings highlight the importance of considering sociodemographic and substance-specific variability and may help identify risk and protective factors preceding adolescent substance use.

An open-access accelerated adult equivalent of the ABCD Study neuroimaging dataset (a-ABCD)

Rapuano KM, Conley MI, Juliano AC, Conan GM, Maza MT, Woodman K, Martinez SA, Earl E, Perrone A, Feczko E, Fair DA, Watts R, Casey BJ, Rosenberg MD. An open-access accelerated adult equivalent of the ABCD Study neuroimaging dataset (a-ABCD). Neuroimage. 2022 Apr 15:119215. doi: 10.1016/j.neuroimage.2022.119215. Epub ahead of print. PMID: 35436615.

As public access to longitudinal developmental datasets like the Adolescent Brain Cognitive Development StudySM (ABCD Study®) increases, so too does the need for resources to benchmark time-dependent effects. Scan-to-scan changes observed with repeated imaging may reflect development but may also reflect practice effects, day-to-day variability in psychological states, and/or measurement noise. Resources that allow disentangling these time-dependent effects will be useful in quantifying actual developmental change. We present an accelerated adult equivalent of the ABCD Study dataset (a-ABCD) using an identical imaging protocol to acquire magnetic resonance imaging (MRI) structural, diffusion-weighted, resting-state and task-based data from eight adults scanned five times over five weeks. We report on the task-based imaging data (n = 7). In-scanner stop-signal (SST), monetary incentive delay (MID), and emotional n-back (EN-back) task behavioral performance did not change across sessions. Post-scan recognition memory for emotional n-back stimuli, however, did improve as participants became more familiar with the stimuli. Functional MRI analyses revealed that patterns of task-based activation reflecting inhibitory control in the SST, reward success in the MID task, and working memory in the EN-back task were more similar within individuals across repeated scan sessions than between individuals. Within-subject, activity was more consistent across sessions during the EN-back task than in the SST and MID task, demonstrating differences in fMRI data reliability as a function of task. The a-ABCD dataset provides a unique testbed for characterizing the reliability of brain function, structure, and behavior across imaging modalities in adulthood and benchmarking neurodevelopmental change observed in the open-access ABCD Study.

Computational modeling of the N-Back task in the ABCD study: associations of drift diffusion model parameters to polygenic scores of mental disorders and cardiometabolic diseases

Pedersen ML, Alnæs D, van der Meer D, Fernandez-Cabello S, Berthet P, Dahl A, Kjelkenes R, Schwarz E, Thompson WK, Barch DM, Andreassen OA, Westlye LT. Computational modeling of the N-Back task in the ABCD study: associations of drift diffusion model parameters to polygenic scores of mental disorders and cardiometabolic diseases. Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Apr 12:S2451-9022(22)00078-7. doi: 10.1016/j.bpsc.2022.03.012. Epub ahead of print. PMID: 35427796.

Background: Cognitive dysfunction is common in mental disorders and represents a potential risk factor in childhood. The nature and extent of associations between childhood cognitive function and polygenic risk for mental disorders is unclear. We applied computational modeling to gain insight into mechanistic processes underlying decision making and working memory in childhood and their associations with PRS for mental disorders and comorbid cardiometabolic diseases.

Methods: We used the drift diffusion model to infer latent computational processes underlying decision-making and working memory during the N-back task in 3707 children aged 9-10 from the ABCD Study. SNP-based heritability was estimated for cognitive phenotypes, including computational parameters, aggregated N-back task performance and neurocognitive assessments. PRS was calculated for Alzheimer’s disease (AD), bipolar disorder, coronary artery disease (CAD), major depressive disorder, obsessive-compulsive disorder, schizophrenia and type 2 diabetes.

Results: Heritability estimates of cognitive phenotypes ranged from 12 to 38%. Bayesian mixed models revealed that slower accumulation of evidence was associated with higher PRS for CAD and schizophrenia. Longer non-decision time was associated with higher PRS for AD and lower PRS for CAD. Narrower decision threshold was associated with higher PRS for CAD. Load-dependent effects on non-decision time and decision threshold were associated with PRS for AD and CAD, respectively. Aggregated neurocognitive test scores were not associated with PRS for any of the mental or cardiometabolic phenotypes.

Conclusions: We identified distinct associations between computational cognitive processes to genetic risk for mental illness and cardiometabolic disease, which could represent childhood cognitive risk factors.

Attention-Deficit/Hyperactivity Disorder: Restricted Phenotypes Prevalence, Comorbidity, and Polygenic Risk Sensitivity in the ABCD Baseline Cohort

Cordova MM, Antovich DM, Ryabinin P, Neighbor C, Mooney MA, Dieckmann NF, Miranda-Dominguez O, Nagel BJ, Fair DA, Nigg JT. Attention-Deficit/Hyperactivity Disorder: Restricted Phenotypes Prevalence, Comorbidity, and Polygenic Risk Sensitivity in the ABCD Baseline Cohort. J Am Acad Child Adolesc Psychiatry. 2022 Apr 12:S0890-8567(22)00190-3. doi: 10.1016/j.jaac.2022.03.030. Epub ahead of print. PMID: 35427730.

Objective: To evaluate the prevalence and major comorbidities of ADHD using different operational definitions in a newly available national dataset and to test the utility of operational definitions against genetic and cognitive correlates.

Method: The US Adolescent Brain Cognitive Development (ABCD) Study enrolled 11,878 children aged 9-10 years at baseline. ADHD prevalence, comorbidity, and association with polygenic risk score and laboratory-assessed executive functions were calculated at 4 thresholds of ADHD phenotype restrictiveness. Bias from missingness, sampling, and nesting were addressed statistically.

Results: Prevalence of current ADHD for 9- to 10-year old children was 3.53% (95% CI 3.14%-3.92%) when Computerized Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS-COMP) score and parent and teacher ratings were required to converge. Of ADHD cases so defined, 70% had a comorbid psychiatric disorder. After control for overlapping comorbidity and ruling out for psychosis or low IQ, 30.9% (95% CI 25.7%-36.7%) had a comorbid disruptive behavior disorder, 27.4% (95% CI 22.3%-33.1%) had an anxiety or fear disorder, and 2.1% (95% CI 1.2%-3.8%) had a mood disorder. Children in the top decile of polygenic load incurred a 63% increased chance of having ADHD vs the bottom half of polygenic load (p < .01)-an effect detected only with a stringent phenotype definition. Dimensional latent variables for irritability, externalizing, and ADHD yielded convergent results for cognitive correlates.

Conclusion: This fresh estimate of national prevalence of ADHD in the United States suggests that the DSM-5 definition requiring multiple informants yields a prevalence of about 3.5%. Results may inform further ADHD studies in the ABCD sample.

Neurodevelopmental Profiles in Adolescence: Leveraging Data From the Landmark Adolescent Brain Cognitive Development Study

Mewton L, Squeglia L. Neurodevelopmental Profiles in Adolescence: Leveraging Data From the Landmark Adolescent Brain Cognitive Development Study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Apr;7(4):343-345. doi: 10.1016/j.bpsc.2022.01.005. PMID: 35396019.

Common variants contribute to intrinsic human brain functional networks

Zhao, B., Li, T., Smith, S.M. et al. Common variants contribute to intrinsic human brain functional networks. Nat Genet (2022). https://doi.org/10.1038/s41588-022-01039-6

The human brain forms functional networks of correlated activity, which have been linked with both cognitive and clinical outcomes. However, the genetic variants affecting brain function are largely unknown. Here, we used resting-state functional magnetic resonance images from 47,276 individuals to discover and validate common genetic variants influencing intrinsic brain activity. We identified 45 new genetic regions associated with brain functional signatures (P < 2.8 × 10−11), including associations to the central executive, default mode, and salience networks involved in the triple-network model of psychopathology. A number of brain activity-associated loci colocalized with brain disorders (e.g., the APOE ε4 locus with Alzheimer’s disease). Variation in brain function was genetically correlated with brain disorders, such as major depressive disorder and schizophrenia. Together, our study provides a step forward in understanding the genetic architecture of brain functional networks and their genetic links to brain-related complex traits and disorders.

Identification and Validation of Distinct Latent Neurodevelopmental Profiles in the Adolescent Brain and Cognitive Development Study

Lichenstein SD, Roos C, Kohler R, Kiluk B, Carroll KM, Worhunsky PD, Witkiewitz K, Yip SW. Identification and Validation of Distinct Latent Neurodevelopmental Profiles in the Adolescent Brain and Cognitive Development Study, Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Volume 7, Issue 4, April 2022, Pages 352-361, https://doi.org/10.1016/j.bpsc.2021.02.013

Background
Regardless of the precise mechanism, all neurodevelopmental models of risk assume that, at the population level, there exist subgroups of individuals that share similar patterns of neural function and development—and that these subgroups somehow relate to psychiatric risk. However, the existence of multiple neurodevelopmental subgroups at the population level has not been assessed previously.

Methods
In the current study, cross-validated latent profile analysis was used to test for the presence of empirically derived, brain-based developmental subgroups using functional magnetic resonance imaging data from 6758 individuals (49.4% female; mean age = 9.94 years) in the Adolescent Brain and Cognitive Development (ABCD) study wave 1 release. Data were randomly split into training and testing samples.

Results
Analyses in the training sample (n = 3379) identified a seven-profile solution (entropy = 0.880) that was replicated in the held-out testing data (n = 3379, entropy = 0.890). Identified subgroups included a moderate group (66.8%), high reward (4.3%) and low reward (4.0%) groups, high inhibition (9.8%) and low inhibition (6.7%) groups, and high emotion regulation (4.0%) and low emotion regulation (4.3%) groups. Relative to the moderate group, other subgroups were characterized by more males (χ2 = 24.10, p = .0005), higher proportions of individuals from lower-income households (χ2 = 122.17, p < .0001), poorer cognitive performance (ps < .0001), more screen time (F = 6.80, p < .0001), heightened impulsivity (ps < .006), and higher rates of neurodevelopmental disorders (χ2 = 26.20, p = .0002).

Conclusions
These data demonstrate the existence of multiple, distinct neurodevelopmental subgroups at the population level. They indicate that these empirically derived, brain-based developmental profiles relate to differences in clinical features, even at a young age, and prior to the peak period of risk for the development of psychopathology.

Association between racial/ethnic discrimination and pubertal development in early adolescence

Argabright ST, Moore TM, Visoki E, DiDomenico GE, Taylor JH, Barzilay R. Association between racial/ethnic discrimination and pubertal development in early adolescence. Psychoneuroendocrinology, Volume 140, June 2022, 105727, https://doi.org/10.1016/j.psyneuen.2022.105727

Racial health disparities in the United States are a major concern, with Black or African Americans experiencing more morbidity and mortality at earlier ages compared to White Americans. More data is needed on the biological underpinnings of this phenomenon. One potential explanation for racial health disparities is that of accelerated aging, which is associated with increased stress exposure. Black Americans face disproportionate levels of environmental stress, specifically racial/ethnic discrimination. Here we investigated associations between self-reported experiences of discrimination and pubertal development (PD) in a diverse sample of young American adolescents (N=11,235, mean age 10.9 years, 20.5% Black participants) from the Adolescent Brain Cognitive Development (ABCD) Study. Compared to their non-Black counterparts, Black youth experienced more racial/ethnic discrimination in the past year (10.4% vs 3.1%) and had a greater likelihood of being in late/post-pubertal status (3.6% vs 1.5% in boys, 21.3% vs 11.4% in girls). In both sexes, multivariable regression models run in the full sample revealed a cross-sectional association of experiences of racial/ethnic discrimination with pubertal development (boys: standardized beta [β]=0.123, P<.001; girls: β=0.110, P<.001) covarying for demographics, BMI, and dietary habits. Associations remained significant when controlling for multiple other environmental confounders including other forms of (non-racial/ethnic) discrimination and other environmental adversities including poverty and negative life events, and when using parent-reported assessment of pubertal development. Furthermore, racial/ethnic discrimination was associated with elevated estradiol levels in girls (β=0.057, P=.002). Findings suggest an association between experiences of discrimination and pubertal development that is independent of multiple environmental stressors. Future longitudinal studies are warranted to establish causal mechanism.

Brain charts for the human lifespan

Bethlehem, R.A.I., Seidlitz, J., White, S.R. et al. Brain charts for the human lifespan. Nature (2022). Published: 06 April 2022. https://doi.org/10.1038/s41586-022-04554-y

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Prenatal cannabis exposure predicts attention problems, without changes on fMRI in adolescents

Cioffredi LA, Anderson H, Loso H, East J, Nguyen P, Garavan H, Potter A. Prenatal cannabis exposure predicts attention problems, without changes on fMRI in adolescents. Neurotoxicol Teratol. Volume 91, May–June 2022, 107089, https://doi.org/10.1016/j.ntt.2022.107089

Objectives: We hypothesized that prenatal cannabis exposure (PCE) would be associated with increased attention problems and altered neurocognition in young adolescents.

Methods: Data were obtained from the Adolescent Brain Cognitive Development (ABCD study®), a cohort of approximately 12,000 children. Presence or absence of PCE after knowledge of pregnancy was measured by caregiver report. All participants with PCE (N = 224) were included and compared to two control groups; those matched on tobacco and alcohol exposure and those without prenatal tobacco or alcohol exposures. Outcomes were measured with the ABCD baseline assessment when participants were 9-10 years old and included attention, internalizing, externalizing and total problems scales on the Child Behavior Checklist (CBCL). Teacher reports were used when available. Mixed effects modeling assessed the association between PCE and outcomes controlling for parental psychopathology, prematurity and socioeconomic status. For participants with available data, patterns of brain activity during three fMRI tasks (the Stop Signal Task measuring response inhibition, the Monetary Incentive Delay (MID) task measuring reward processing and the EN-Back task measuring working memory) were analyzed using Permutation Analyses of the Linear Model.

Results: Compared to both control groups, participants with PCE had significantly higher attention problems, externalizing, and total problem scores. PCE did not impact cognitive performance or patterns of brain activation during fMRI tasks.

Conclusions: There are long-term associations between PCE and early adolescent attention and behavioral problems. These are not reflected in cognitive performance or task fMRI measures, a finding that is consistent with reports that fewer than half of children with ADHD have any specific cognitive deficit (Nigg et al., 2005; Willcutt et al., 2005). The young age of the sample may also relate to this finding and future investigation of neurodevelopmental trajectories of youth with PCE is warranted.

Evaluation of Brain Alterations and Behavior in Children With Low Levels of Prenatal Alcohol Exposure

Long X, Lebel C. Evaluation of Brain Alterations and Behavior in Children With Low Levels of Prenatal Alcohol Exposure. JAMA Netw Open. 2022 Apr 1;5(4):e225972. doi: 10.1001/jamanetworkopen.2022.5972. PMID: 35380644.

Importance: High levels of prenatal alcohol exposure (PAE) are associated with widespread behavioral and cognitive problems as well as structural alterations of the brain. However, it remains unclear whether low levels of PAE affect brain structure and function, and prior studies generally have not had well-matched control populations (eg, for sociodemographic variables).

Objective: To compare structural brain alterations and behavioral changes in children with lower levels of PAE with those of well-matched controls with no PAE.

Design, setting, and participants: In this cross-sectional study, participants were selected from the Adolescent Brain Cognitive Development study. Children with PAE were compared with controls matched for age, sex, family income, maternal educational level, and caregiver status. Neither group had prenatal exposure to other adverse substances (eg, tobacco, cannabis, illicit drugs). Data were collected from September 1, 2016, to November 15, 2018, and analyzed from October 14, 2020, to February 14, 2022.

Exposures: Diffusion tensor imaging, resting-state functional magnetic resonance imaging (MRI), and Child Behavior Checklist (CBCL) administration.

Main outcomes and measures: Fractional anisotropy (FA); mean, axial, and radial diffusivity from diffusion tensor imaging; brain functional signal variations from functional MRI; and several scores, including internalizing and externalizing behavior problems, from the CBCL. Spearman correlation coefficients between diffusion tensor imaging and functional MRI measures and the CBCL scores were calculated.

Results: A total of 270 children were included in the analysis (mean [SD] age, 9.86 [0.46] years; 141 female [52.2%] and 129 male [47.8%]), consisting of 135 children with PAE (mean [SD] age, 9.85 [0.65] years; 73 female [54.1%] and 62 male [45.9%]) (mean exposure, 1 drink/wk) and 135 unexposed controls (mean [SD] age, 9.87 [0.04] years; 68 female [50.4%] and 67 male [49.6%]). Children with PAE had lower mean (SD) FA in white matter of the left postcentral (0.35 [0.05] vs 0.36 [0.04]; mean difference, -0.02 [95% CI, -0.03 to -0.01]), left inferior parietal (0.31 [0.07] vs 0.33 [0.06]; mean difference, -0.03 [95% CI, -0.04 to -0.01]), left planum temporale (0.26 [0.04] vs 0.28 [0.03]; mean difference, -0.02 [95% CI, -0.03 to -0.01]), left inferior occipital (0.30 [0.07] vs 0.32 [0.05]; mean difference, -0.03 [95% CI, -0.04 to -0.01]), and right middle occipital (0.30 [0.04] vs 0.31 [0.04]; mean difference, -0.01 [95% CI, -0.02 to -0.01]) areas compared with controls, and higher FA in the gray matter of the putamen (0.22 [0.03] vs 0.21 [0.02]; mean difference, 0.01 [95% CI, 0.005-0.02]). Externalizing behavior scores were higher (worse) in children with PAE than in controls (mean [SD], 45.2 [9.0] vs 42.8 [9.0]; mean difference, 2.39 [95% CI, 0.30-4.47]). Several of these regions had significant group-behavior interactions, such that the higher FA was associated with less problematic behaviors in controls (ρ range, -0.24 to -0.08) but no associations were present in the PAE group (ρ range, 0.02-0.16).

Conclusions and relevance: In this cross-sectional study, children with low levels of PAE had lower FA and more behavioral problems compared with a well-matched control group. These results suggest that PAE, even in small amounts, has a measurable effect on brain structure in children.

Regional gray matter abnormalities in pre-adolescent binge eating disorder: A voxel-based morphometry study

Murray SB, Duval CJ, Balkchyan AA, Cabeen RP, Nagata JM, Toga AW, Siegel SJ, Jann K. Regional gray matter abnormalities in pre-adolescent binge eating disorder: A voxel-based morphometry study. Psychiatry Research. Volume 310, April 2022, 114473, https://doi.org/10.1016/j.psychres.2022.114473

Background
Binge eating disorder (BED) is a pernicious psychiatric disorder which is linked with an array of multisystemic organ morbidity, broad psychiatric morbidity, and obesity. Despite behavioral markers often developing in early childhood, the neurobiological markers of early-onset BED remain understudied, and developmental pathophysiology remains poorly understood.

Methods
71 preadolescent children (aged 9–10-years) with BED and 74 age, BMI and developmentally matched control children were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development (ABCD) Study. We investigated group differences in gray matter density (GMD) via voxel-based morphometry (VBM). We additionally performed region of interest analyses, assessing the association between GMD in nodes of the reward (orbitofrontal cortex; OFC) and inhibitory control (dorsolateral prefrontal cortex; dlPFC) networks, and parent-reported behavioral inhibition and approach tendencies.

Results
Diffuse elevations in cortical GMD were noted in those with BED, which spanned prefrontal, parietal, and temporal regions. No areas of reduced GMD were noted in those with BED. No alterations in subcortical GMD were noted. Brain-behavioral associations suggest a distinct and negative relationship between GMD in the OFC and dlPFC, respectively, and self-reported markers of hedonic behavioral approach tendencies.

Conclusions
Early-onset BED may be characterized by diffuse morphological abnormalities in gray matter density, suggesting alterations in cortical architecture which may reflect decreased synaptic pruning and arborization, or decreased myelinated fibers and therefore inter-regional afferents.

Neurobiological, familial and genetic risk factors for dimensional psychopathology in the Adolescent Brain Cognitive Development study

Wainberg M, Jacobs GR, Voineskos AN, Tripathy SJ. Neurobiological, familial and genetic risk factors for dimensional psychopathology in the Adolescent Brain Cognitive Development study. Mol Psychiatry. 2022 Mar 31. doi: 10.1038/s41380-022-01522-w. Epub ahead of print. PMID: 35361904.

Background: Adolescence is a key period for brain development and the emergence of psychopathology. The Adolescent Brain Cognitive Development (ABCD) study was created to study the biopsychosocial factors underlying healthy and pathological brain development during this period, and comprises the world’s largest youth cohort with neuroimaging, family history and genetic data.

Methods: We examined 9856 unrelated 9-to-10-year-old participants in the ABCD study drawn from 21 sites across the United States, of which 7662 had multimodal magnetic resonance imaging scans passing quality control, and 4447 were non-Hispanic white and used for polygenic risk score analyses. Using data available at baseline, we associated eight ‘syndrome scale scores’ from the Child Behavior Checklist-summarizing anxious/depressed symptoms, withdrawn/depressed symptoms, somatic complaints, social problems, thought problems, attention problems, rule-breaking behavior, and aggressive behavior-with resting-state functional and structural brain magnetic resonance imaging measures; eight indicators of family history of psychopathology; and polygenic risk scores for major depression, bipolar disorder, schizophrenia, attention deficit hyperactivity disorder (ADHD) and anorexia nervosa. As a sensitivity analysis, we excluded participants with clinically significant (>97th percentile) or borderline (93rd-97th percentile) scores for each dimension.

Results: Most Child Behavior Checklist dimensions were associated with reduced functional connectivity within one or more of four large-scale brain networks-default mode, cingulo-parietal, dorsal attention, and retrosplenial-temporal. Several dimensions were also associated with increased functional connectivity between the default mode, dorsal attention, ventral attention and cingulo-opercular networks. Conversely, almost no global or regional brain structural measures were associated with any of the dimensions. Every family history indicator was associated with every dimension. Major depression polygenic risk was associated with six of the eight dimensions, whereas ADHD polygenic risk was exclusively associated with attention problems and externalizing behavior (rule-breaking and aggressive behavior). Bipolar disorder, schizophrenia and anorexia nervosa polygenic risk were not associated with any of the dimensions. Many associations remained statistically significant even after excluding participants with clinically significant or borderline psychopathology, suggesting that the same risk factors that contribute to clinically significant psychopathology also contribute to continuous variation within the clinically normal range.

Conclusions: This study codifies neurobiological, familial and genetic risk factors for dimensional psychopathology across a population-scale cohort of community-dwelling preadolescents. Future efforts are needed to understand how these multiple modalities of risk intersect to influence trajectories of psychopathology into late adolescence and adulthood.

Automated Multiclass Artifact Detection in Diffusion MRI Volumes via 3D Residual Squeeze-and-Excitation Convolutional Neural Networks

Ettehadi N, Kashyap P, Zhang X, Wang Y, Semanek D, Desai K, Guo J, Posner J, Laine AF. Automated Multiclass Artifact Detection in Diffusion MRI Volumes via 3D Residual Squeeze-and-Excitation Convolutional Neural Networks. Front Hum Neurosci. 2022 Mar 30;16:877326. doi: 10.3389/fnhum.2022.877326. PMID: 35431841; PMCID: PMC9005752.

Diffusion MRI (dMRI) is widely used to investigate neuronal and structural development of brain. dMRI data is often contaminated with various types of artifacts. Hence, artifact type identification in dMRI volumes is an essential pre-processing step prior to carrying out any further analysis. Manual artifact identification amongst a large pool of dMRI data is a highly labor-intensive task. Previous attempts at automating this process are often limited to a binary classification (“poor” vs. “good” quality) of the dMRI volumes or focus on detecting a single type of artifact (e.g., motion, Eddy currents, etc.). In this work, we propose a deep learning-based automated multiclass artifact classifier for dMRI volumes. Our proposed framework operates in 2 steps. In the first step, the model predicts labels associated with 3D mutually exclusive collectively exhaustive (MECE) sub-volumes or “slabs” extracted from whole dMRI volumes. In the second step, through a voting process, the model outputs the artifact class present in the whole volume under investigation. We used two different datasets for training and evaluating our model. Specifically, we utilized 2,494 poor-quality dMRI volumes from the Adolescent Brain Cognitive Development (ABCD) and 4,226 from the Healthy Brain Network (HBN) dataset. Our results demonstrate accurate multiclass volume-level main artifact type prediction with 96.61 and 97.52% average accuracies on the ABCD and HBN test sets, respectively. Finally, in order to demonstrate the effectiveness of the proposed framework in dMRI pre-processing pipelines, we conducted a proof-of-concept dMRI analysis exploring the relationship between whole-brain fractional anisotropy (FA) and participant age, to test whether the use of our model improves the brain-age association.

Understanding Associations Between Race/Ethnicity, Experiences of Discrimination, and Psychotic-like Experiences in Middle Childhood

Karcher NR, Klaunig MJ, Elsayed NM, Taylor RL, Jay SY, Schiffman J. Understanding Associations Between Race/Ethnicity, Experiences of Discrimination, and Psychotic-like Experiences in Middle Childhood. J Am Acad Child Adolesc Psychiatry. 2022 Mar 29:S0890-8567(22)00180-0. doi: 10.1016/j.jaac.2022.03.025. Epub ahead of print. PMID: 35378237.

Objective: The present study aimed to examine factors that may account for race/ethnicity differences in psychotic-like experiences (PLEs) in a middle childhood sample, including evidence for experiences of discrimination as a psychosocial mediator of these differences.

Method: Within a sample of 10,839 9 to 10-year-olds from the Adolescent Brain Cognitive Development℠ study, we compared PLEs across racial/ethnic groups. We also examined whether experiences of discrimination indirectly linked racial/ethnic identity and PLEs, and whether social support moderated this indirect association.

Results: Results indicated differences between racial/ethnic groups in the endorsement of PLEs, such that Black and Hispanic participants endorsed higher levels of PLEs as compared to Asian, Multiracial/Multiethnic, and White individuals. We found these differences were accounted for in part by experiences of discrimination, an indirect effect that was in turn attenuated by increased social support.

Conclusion: This is the first study to suggest that the experience of discrimination may indirectly link the association between racial/ethnic differences and endorsement of PLEs using the PQ-BC, and additionally that social support may act as a moderator of this mediation. Results provide evidence that social inequities such as racial discrimination may contribute to increases in psychotic-like experiences. These findings shed further light on a possible mechanism linking structural racism and mental health inequities for people in minoritized groups.

Substance use onset in high-risk 9-13 year-olds in the ABCD study

Wade NE, Tapert SF, Lisdahl KM, Huestis MA, Haist F. Substance use onset in high-risk 9-13 year-olds in the ABCD study. Neurotoxicol Teratol. 2022 May-Jun;91:107090. doi: 10.1016/j.ntt.2022.107090. Epub 2022 Mar 24. PMID: 35341934.

Aim: A key aim of the Adolescent Brain Cognitive Development℠ (ABCD) Study is to document substance use onset, patterns, and sequelae across adolescent development. However, substance use misreporting can obscure accurate drug use characterization. Hair toxicology provides objective historical substance use data but is rarely used in studies of youth. Here, we compare objective hair toxicology results with self-reported substance use in high-risk youth.

Methods: A literature-based substance use risk algorithm prioritized 696 ABCD Study® hair samples from 677 participants for analysis at baseline, and 1 and 2-year follow-ups (spanning ages 9-13). Chi-square and t-tests assessed differences between participants’ demographics, positive and negative hair tests, risk-for-use algorithm scores, and self-reported substance use.

Results: Hair testing confirmed that 17% of at-risk 9-13 year-olds hair samples had evidence of past 3-month use of one (n = 97), two (n = 14), three (n = 2), or four (n = 2) drug classes. After considering prescribed medication and self-reported substance use, 10% had a positive test indicating substance use that was not reported. Participants with any positive hair result reported less sipping of alcohol (p < 0.001) and scored higher on the risk-for-use algorithm (p < 0.001) than those with negative toxicology results.

Conclusions: 10% of hair samples from at-risk 9-13 year-olds tested positive for at least one unreported substance, suggesting underreporting in high-risk youth when participating in a research study. As hair testing prioritized youth with risk characteristics, the overall extent of underreporting will be calculated in future studies. Nonetheless, hair toxicology was key to characterizing substance use in high-risk youth.

Multi-level predictors of depression symptoms in the Adolescent Brain Cognitive Development (ABCD) study

Ho TC, Shah R, Mishra J, May AC, Tapert SF. Multi-level predictors of depression symptoms in the Adolescent Brain Cognitive Development (ABCD) study. J Child Psychol Psychiatry. 2022 Mar 21. doi: 10.1111/jcpp.13608. Epub ahead of print. PMID: 35307818.

Background: While identifying risk factors for adolescent depression is critical for early prevention and intervention, most studies have sought to understand the role of isolated factors rather than across a broad set of factors. Here, we sought to examine multi-level factors that maximize the prediction of depression symptoms in US children participating in the Adolescent Brain and Cognitive Development (ABCD) study.

Methods: A total of 7,995 participants from ABCD (version 3.0 release) provided complete data at baseline and 1-year follow-up data. Depression symptoms were measured with the Child Behavior Checklist. Predictive features included child demographic, environmental, and structural and resting-state fMRI variables, parental depression history and demographic characteristics. We used linear (elastic net regression, EN) and non-linear (gradient-boosted trees, GBT) predictive models to identify which set of features maximized prediction of depression symptoms at baseline and, separately, at 1-year follow-up.

Results: Both linear and non-linear models achieved comparable results for predicting baseline (EN: MAE = 3.757; R2 = 0.156; GBT: MAE = 3.761; R2 = 0.147) and 1-year follow-up (EN: MAE = 4.255; R2 = 0.103; GBT: MAE = 4.262; R2 = 0.089) depression. Parental history of depression, greater family conflict, and shorter child sleep duration were among the top predictors of concurrent and future child depression symptoms across both models. Although resting-state fMRI features were relatively weaker predictors, functional connectivity of the caudate was consistently the strongest neural feature associated with depression symptoms at both timepoints.

Conclusions: Consistent with prior research, parental mental health, family environment, and child sleep quality are important risk factors for youth depression. Functional connectivity of the caudate is a relatively weaker predictor of depression symptoms but may represent a biomarker for depression risk.

Aberrant functional connectivity between reward and inhibitory control networks in pre-adolescent binge eating disorder

Murray SB, Alba C, Duval CJ, Nagata JM, Cabeen RP, Lee DJ, Toga AW, Siegel SJ, Jann K. Aberrant functional connectivity between reward and inhibitory control networks in pre-adolescent binge eating disorder. Psychol Med. 2022 Mar 18:1-10. doi: 10.1017/S0033291722000514. Epub ahead of print. PMID: 35301976.

Background: Behavioral features of binge eating disorder (BED) suggest abnormalities in reward and inhibitory control. Studies of adult populations suggest functional abnormalities in reward and inhibitory control networks. Despite behavioral markers often developing in children, the neurobiology of pediatric BED remains unstudied.

Methods: 58 pre-adolescent children (aged 9-10-years) with BED (mBMI = 25.05; s.d. = 5.40) and 66 age, BMI and developmentally matched control children (mBMI = 25.78; s.d. = 0.33) were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development (ABCD) Study. We investigated group differences in resting-state functional MRI functional connectivity (FC) within and between reward and inhibitory control networks. A seed-based approach was employed to assess nodes in the reward [orbitofrontal cortex (OFC), nucleus accumbens, amygdala] and inhibitory control [dorsolateral prefrontal cortex, anterior cingulate cortex (ACC)] networks via hypothesis-driven seed-to-seed analyses, and secondary seed-to-voxel analyses.

Results: Findings revealed reduced FC between the dlPFC and amygdala, and between the ACC and OFC in pre-adolescent children with BED, relative to controls. These findings indicating aberrant connectivity between nodes of inhibitory control and reward networks were corroborated by the whole-brain FC analyses.

Conclusions: Early-onset BED may be characterized by diffuse abnormalities in the functional synergy between reward and cognitive control networks, without perturbations within reward and inhibitory control networks, respectively. The decreased capacity to regulate a reward-driven pursuit of hedonic foods, which is characteristic of BED, may in part, rest on this dysconnectivity between reward and inhibitory control networks.

Cross-ethnicity/race generalization failure of behavioral prediction from resting-state functional connectivity

Li J, Bzdok D, Chen J, Tam A, Qi Rong OOI L, Holmes AJ, GE T, Patil KR, Jabbi M, Eickhoff SB, Thomas Yeo BT, and Genon S. Cross-ethnicity/race generalization failure of behavioral prediction from resting-state functional connectivity. Science Advances, Mar 2022, Vol 8, Issue 11, DOI: 10.1126/sciadv.abj1812

Algorithmic biases that favor majority populations pose a key challenge to the application of machine learning for precision medicine. Here, we assessed such bias in prediction models of behavioral phenotypes from brain functional magnetic resonance imaging. We examined the prediction bias using two independent datasets (preadolescent versus adult) of mixed ethnic/racial composition. When predictive models were trained on data dominated by white Americans (WA), out-of-sample prediction errors were generally higher for African Americans (AA) than for WA. This bias toward WA corresponds to more WA-like brain-behavior association patterns learned by the models. When models were trained on AA only, compared to training only on WA or an equal number of AA and WA participants, AA prediction accuracy improved but stayed below that for WA. Overall, the results point to the need for caution and further research regarding the application of current brain-behavior prediction models in minority populations.

Reproducible brain-wide association studies require thousands of individuals

Marek S, Tervo-Clemmens B, Calabro FJ, Montez DF, Kay BP, Hatoum AS, Donohue MR, Foran W, Miller RL, Hendrickson TJ, Malone SM, Kandala S, Feczko E, Miranda-Dominguez O, Graham AM, Earl EA, Perrone AJ, Cordova M, Doyle O, Moore LA, Conan GM, Uriarte J, Snider K, Lynch BJ, Wilgenbusch JC, Pengo T, Tam A, Chen J, Newbold DJ, Zheng A, Seider NA, Van AN, Metoki A, Chauvin RJ, Laumann TO, Greene DJ, Petersen SE, Garavan H, Thompson WK, Nichols TE, Yeo BTT, Barch DM, Luna B, Fair DA, Dosenbach NUF. Reproducible brain-wide association studies require thousands of individuals. Nature. March 16, 2022. DOI: 10.1038/s41586-022-04492-9

Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions1,2,3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)). Such BWAS have typically relied on sample sizes appropriate for classical brain mapping4 (the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain–behavioural phenotype associations5,6. Here we used three of the largest neuroimaging datasets currently available—with a total sample size of around 50,000 individuals—to quantify BWAS effect sizes and reproducibility as a function of sample size. BWAS associations were smaller than previously thought, resulting in statistically underpowered studies, inflated effect sizes and replication failures at typical sample sizes. As sample sizes grew into the thousands, replication rates began to improve and effect size inflation decreased. More robust BWAS effects were detected for functional MRI (versus structural), cognitive tests (versus mental health questionnaires) and multivariate methods (versus univariate). Smaller than expected brain–phenotype associations and variability across population subsamples can explain widespread BWAS replication failures. In contrast to non-BWAS approaches with larger effects (for example, lesions, interventions and within-person), BWAS reproducibility requires samples with thousands of individuals.

10. Screen Time and Moderate-to-Vigorous Intensity Physical Activity Among Adolescents During the COVID-19 Pandemic: Findings From the Adolescent Brain Cognitive Development Study

Nagata JM, Cortez CA, Dooley EE, Iyer P, Ganson KT, Bibbins-Domingo K, Baker FC, Gabriel KP. 10. Screen Time and Moderate-to-Vigorous Intensity Physical Activity Among Adolescents During the COVID-19 Pandemic: Findings From the Adolescent Brain Cognitive Development Study. Volume 70, Issue 4, Supplement, S6, APRIL 01, 2022. DOI:https://doi.org/10.1016/j.jadohealth.2022.01.014

Purpose
The novel coronavirus 2019 (COVID-19) pandemic and subsequent stay-at-home mandates, remote learning, and social distancing requirements led to changes in nearly all facets of adolescents’ lives; however, the pandemic’s effect on adolescent screen time and physical activity has not been characterized using national data from the U.S. The aim of this study was to evaluate adolescents’ screen use and moderate-to-vigorous intensity physical activity (MVPA) during the COVID-19 pandemic by sociodemographic characteristics, and to determine mental health and resiliency factors associated with screen use and MVPA.

Methods
Data from the Year 1 (2017-2019) and May 2020 COVID-19 survey of the Adolescent Brain Cognitive Development (ABCD) Study, a national prospective cohort study in the U.S., were analyzed. Average hours per day spent on six forms of screen time were summed to calculate a total daily screen time measure, excluding hours spent on school-related work. MVPA was quantified as the product of reported duration and frequency (hours per week; h∙wk-1), which was further summarized as the proportion meeting age-appropriate 2018 Physical Activity Guidelines for Americans (i.e., 60 minutes per day). Mental health and resiliency measures were also collected. Regression models examined associations between mental health or resiliency measures and screen time or MVPA during the pandemic.

Results
The sample consisted of 5,153 adolescents predominantly ages 12-13 years, with 50.6% female and 39.5% racial/ethnic minorities. During the pandemic, adolescents reported an average of 7.70 hours of screen use per day, mostly spent on watching/streaming videos, movies, or television shows (2.42 hours), multi-player gaming (1.44 hours), and single-player gaming (1.17 hours). Median MVPA was 2 hours per week (IQR 0, 6) during the pandemic. Overall, the percentage of the cohort meeting MVPA guidelines decreased from 16.1% (pre-pandemic) to 8.9% during the pandemic. Racial/ethnic minorities and adolescents from lower socioeconomic backgrounds reported higher daily screen use and were significantly less likely to meet MVPA guidelines during the pandemic. In adjusted regression models, poorer mental health and greater perceived stress were associated with higher total screen use. Poorer emotional well-being, COVID-related worry, and stress were associated with lower MVPA. More social support and coping behaviors were associated with lower total screen use and higher MVPA during the pandemic.

Conclusions
In this large, national sample of adolescents, we found that average total daily recreational screen use was 7.7 hours per day, representing a doubling of pre-pandemic estimates from the same cohort (3.8 hours). The proportion of those meeting MVPA Guidelines was lower during the COVID-19 pandemic, with significant disparities by race and class. Disparities across racial/ethnic and income groups in adolescents may be due to structural and systemic factors (e.g., built or neighborhood environment, access to resources) – all of which have been amplified in the COVID-19 pandemic. Interventions to promote social support and coping behaviors may reduce screen use and improve MVPA levels among adolescents during and post-pandemic.

Explaining the Association Between Urbanicity and Psychotic-Like Experiences in Pre-Adolescence: The Indirect Effect of Urban Exposures

Saxena A, Dodell-Feder D. Explaining the Association Between Urbanicity and Psychotic-Like Experiences in Pre-Adolescence: The Indirect Effect of Urban Exposures. Front. Psychiatry, 11 March 2022 | https://doi.org/10.3389/fpsyt.2022.831089

Urban living is a growing worldwide phenomenon with more than two-thirds of people expected to live in cities by 2050. Although there are many benefits to living in an urban environment, urbanicity has also been associated with deleterious health outcomes, including increased risk for psychotic outcomes particularly when the urban exposure occurs in pre-adolescence. However, the mechanisms underlying this association is unclear. Here, we utilize one-year follow-up data from a large (N=7,979), nationwide study of pre-adolescence in the United States to clarify why urbanicity (i.e., census-tract population density) might impact psychotic-like experiences (PLE) by looking at the indirect effect of eight candidate urbanicity-related physical (e.g., pollution) and social (e.g., poverty) exposures. Consistent with other work, we found that of the evaluated exposures related to urbanicity, several were also related to increased number of PLE: PM2.5, proximity to roads, census-level homes at-risk for exposure to lead paint, census-level poverty, and census-level income-disparity. These same urban-related exposures were also related to the persistence of PLE after 1 year, but not new onset of PLE. Mediation analysis revealed that a substantial proportion the urbanicity-PLE association (number and persistence) could be explained by PM2.5 (23–44%), families in poverty (68–93%), and income disparity (67–80%). Together, these findings suggest that specific urban-related exposures contribute to the existence and maintenance, but not onset of PLE, which might help to explain why those in urban environments are disproportionately at-risk for psychosis and point toward areas for public health intervention.

Characterizing the Neural Correlates of Response Inhibition and Error Processing in Children With Symptoms of Irritability and/or Attention-Deficit/Hyperactivity Disorder in the ABCD Study®

Lee KS, Xiao J, Luo J, Leibenluft E, Liew Z, Tseng WL. Characterizing the Neural Correlates of Response Inhibition and Error Processing in Children With Symptoms of Irritability and/or Attention-Deficit/Hyperactivity Disorder in the ABCD Study®. Front Psychiatry. 2022 Mar 4;13:803891. doi: 10.3389/fpsyt.2022.803891. PMID: 35308882; PMCID: PMC8931695.

Attention-deficit/hyperactivity disorder (ADHD), characterized by symptoms of inattention and/or hyperactivity and impulsivity, is a neurodevelopmental disorder associated with executive dysfunctions, including response inhibition and error processing. Research has documented a common co-occurrence between ADHD and pediatric irritability. The latter is more characterized by affective symptoms, specifically frequent temper outbursts and low frustration tolerance relative to typically developing peers. Shared and non-shared neural correlates of youths with varied profiles of ADHD and irritability symptoms during childhood remain largely unknown. This study first classified a large sample of youths in the Adolescent Brain Cognitive Development (ABCD) study at baseline into distinct phenotypic groups based on ADHD and irritability symptoms (N = 11,748), and then examined shared and non-shared neural correlates of response inhibition and error processing during the Stop Signal Task in a subset of sample with quality neuroimaging data (N = 5,948). Latent class analysis (LCA) revealed four phenotypic groups, i.e., high ADHD with co-occurring irritability symptoms (n = 787, 6.7%), moderate ADHD with low irritability symptoms (n = 901, 7.7%), high irritability with no ADHD symptoms (n = 279, 2.4%), and typically developing peers with low ADHD and low irritability symptoms (n = 9,781, 83.3%). Latent variable modeling revealed group differences in the neural coactivation network supporting response inhibition in the fronto-parietal regions, but limited differences in error processing across frontal and posterior regions. These neural differences were marked by decreased coactivation in the irritability only group relative to youths with ADHD and co-occurring irritability symptoms and typically developing peers during response inhibition. Together, this study provided initial evidence for differential neural mechanisms of response inhibition associated with ADHD, irritability, and their co-occurrence. Precision medicine attending to individual differences in ADHD and irritability symptoms and the underlying mechanisms are warranted when treating affected children and families.

Understanding patterns of heterogeneity in executive functioning during adolescence: Evidence from population-level data

Chaku N, Barry K, Fowle J, Hoyt LT. Understanding patterns of heterogeneity in executive functioning during adolescence: Evidence from population-level data. Dev Sci. 2022 Mar 3. doi: 10.1111/desc.13256. Epub ahead of print. PMID: 35238432.

Executive functioning (EF) is fundamental to positive development. Yet, little is known about how to best identify and characterize constellations of EF skills that may inform disparate associations between EF and behavior during adolescence. In the current study, cross-validated latent profile analysis (LPA) was used to derive profiles of EF based on measures of inhibitory control, working memory, and cognitive flexibility using data from 11,672 youth (52.2% male, mean age = 9.91 years) in the Adolescent Brain and Cognitive Development study. Four meaningful EF profiles emerged from the data representing Average EF, High EF, Low Inhibitory Control, and Low EF. Boys, youth from low-income households, and early developing youth were more likely to be in profiles distinguished by lower EF. Profile membership also predicted differences in externalizing, internalizing, and other problem behaviors assessed one year later. Findings indicate that youth may have distinct constellations of EF skills with unique impact on behaviors, underscoring the need for person-centered approaches that focus on patterns of individual characteristics Latent profile analysis was used to describe profiles of executive functioning (EF) in a population-level sample of early adolescents Heterogenous constellations of EF were captured by four profiles, distinguished primarily by differences in performance level, but also discordance across tasks. Biological sex, socioeconomic status, and pubertal timing predicted most likely profile membership Profile membership predicted externalizing, internalizing, and problem behaviors assessed a year later.

Performance scaling for structural MRI surface parcellations: a machine learning analysis in the ABCD Study

Hahn S, Owens MM, Yuan D, Juliano AC, Potter A, Garavan H, Allgaier N. Performance scaling for structural MRI surface parcellations: a machine learning analysis in the ABCD Study. Cereb Cortex. 2022 Mar 3:bhac060. doi: 10.1093/cercor/bhac060. Epub ahead of print. PMID: 35238352.

The use of predefined parcellations on surface-based representations of the brain as a method for data reduction is common across neuroimaging studies. In particular, prediction-based studies typically employ parcellation-driven summaries of brain measures as input to predictive algorithms, but the choice of parcellation and its influence on performance is often ignored. Here we employed preprocessed structural magnetic resonance imaging (sMRI) data from the Adolescent Brain Cognitive Development Study® to examine the relationship between 220 parcellations and out-of-sample predictive performance across 45 phenotypic measures in a large sample of 9- to 10-year-old children (N = 9,432). Choice of machine learning (ML) pipeline and use of alternative multiple parcellation-based strategies were also assessed. Relative parcellation performance was dependent on the spatial resolution of the parcellation, with larger number of parcels (up to ~4,000) outperforming coarser parcellations, according to a power-law scaling of between 1/4 and 1/3. Performance was further influenced by the type of parcellation, ML pipeline, and general strategy, with existing literature-based parcellations, a support vector-based pipeline, and ensembling across multiple parcellations, respectively, as the highest performing. These findings highlight the choice of parcellation as an important influence on downstream predictive performance, showing in some cases that switching to a higher resolution parcellation can yield a relatively large boost to performance.

Longitudinal Evidence of a Vicious Cycle Between Nucleus Accumbens Microstructure and Childhood Weight Gai

Rapuano KM, Berrian N, Baskin-Sommers A, Décarie-Spain L, Sharma S, Fulton S, Casey BJ, Watts R. Longitudinal Evidence of a Vicious Cycle Between Nucleus Accumbens Microstructure and Childhood Weight Gain. J Adolesc Health. 2022 Mar 2:S1054-139X(22)00002-7. doi: 10.1016/j.jadohealth.2022.01.002. Epub ahead of print. PMID: 35248457.

Purpose: Pediatric obesity is a growing public health concern. Previous work has observed diet to impact nucleus accumbens (NAcc) inflammation in rodents, measured by the reactive proliferation of glial cells. Recent work in humans has demonstrated a relationship between NAcc cell density-a proxy for neuroinflammation-and weight gain in youth; however, the directionality of this relationship in the developing brain and association with diet remains unknown.

Methods: Waist circumference (WC) and NAcc cell density were collected in a large cohort of children (n > 2,000) participating in the Adolescent Brain Cognitive Development (ABCD) Study (release 3.0) at baseline (9-10 y) and at a Year 2 follow-up (11-12 y). Latent change score modeling (LCSM) was used to disentangle contributions of baseline measures to two-year changes in WC percentile and NAcc cellularity. In addition, the role of NAcc cellularity in mediating the relationship between diet and WC percentile was assessed using dietary intake data collected at Year 2.

Results: LCSM indicates that baseline WC percentile influences change in NAcc cellularity and that baseline NAcc cell density influences change in WC percentile. NAcc cellularity was significantly associated with WC percentile at Year 2 and mediated the relationship between dietary fat consumption and WC percentile.

Conclusions: These results implicate a vicious cycle whereby NAcc cell density biases longitudinal changes in WC percentile and vice versa. Moreover, NAcc cell density may mediate the relationship between diet and weight gain in youth. These findings suggest that diet-induced inflammation of reward circuitry may lead to behavioral changes that further contribute to weight gain.

The role of perceived threats on mental health, social, and neurocognitive youth outcomes: A multicontextual, person-centered approach

Conley MI, Hernandez J, Salvati JM, Gee DG, Baskin-Sommers A. The role of perceived threats on mental health, social, and neurocognitive youth outcomes: A multicontextual, person-centered approach. Dev Psychopathol. 2022 Mar 2:1-22. doi: 10.1017/S095457942100184X. Epub ahead of print. PMID: 35232507.

Perceived threat in youth’s environments can elevate risk for mental health, social, and neurocognitive difficulties throughout the lifespan. However, few studies examine variability in youth’s perceptions of threat across multiple contexts or evaluate outcomes across multiple domains, ultimately limiting our understanding of specific risks associated with perceived threats in different contexts. This study examined associations between perceived threat in youth’s neighborhood, school, and family contexts at ages 9-10 and mental health, social, and neurocognitive outcomes at ages 11-12 within a large US cohort (N = 5525) enrolled in the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). Latent profile analysis revealed four distinct profiles: Low Threat in all contexts, Elevated Family Threat, Elevated Neighborhood Threat, and Elevated Threat in all contexts. Mixed-effect models and post hoc pairwise comparisons showed that youth in Elevated Threat profile had poorer mental health and social outcomes 2 years later. Youth in the Elevated Family Threat profile uniquely showed increased disruptive behavior symptoms, whereas youth in the Elevated Neighborhood Threat profile predominantly displayed increased sleep problems and worse neurocognitive outcomes 2 years later. Together, findings highlight the importance of considering perceptions of threat across multiple contexts to achieve a more nuanced developmental picture.

The pandemic’s toll on young adolescents: Prevention and intervention targets to preserve their mental health

O Kiss, et al. The Pandemic’s Toll on Young Adolescents: Prevention and Intervention Targets to Preserve Their Mental Health. Journal of Adolescent Health, Volume 70, Issue 3, March 2022, Pages 387-395. DOI: 10.1016/j.jadohealth.2021.11.023.  Related press release.

Reliability and Stability Challenges in ABCD Task fMRI Data

Kennedy JT, Harms MP, Korucuoglu O, Astafiev SV, Barch DM, Thompson WK, Bjork JM, Anokhin AP. Reliability and Stability Challenges in ABCD Task fMRI Data. Neuroimage. 2022 Mar 1:119046. doi: 10.1016/j.neuroimage.2022.119046. Epub ahead of print. PMID: 35245674.

Trait stability of measures is an essential requirement for individual differences research. Functional MRI has been increasingly used in studies that rely on the assumption of trait stability, such as attempts to relate task related brain activation to individual differences in behavior and psychopathology. However, recent research using adult samples has questioned the trait stability of task-fMRI measures, as assessed by test-retest correlations. To date, little is known about trait stability of task fMRI in children. Here, we examined within-session reliability and long-term stability of individual differences in task-fMRI measures using fMRI measures of brain activation provided by the Adolescent Brain Cognitive Development (ABCD) Study Release v4.0 as an individual’s average regional activity, using its tasks focused on reward processing, response inhibition, and working memory. We also evaluated the effects of factors potentially affecting reliability and stability. Reliability and stability (quantified as the ratio of non-scanner related stable variance to all variances) was poor in virtually all brain regions, with an average value of .088 and .072 for short term (within-session) reliability and long-term (between-session) stability, respectively, in regions of interest (ROIs) historically-recruited by the tasks. Only one reliability or stability value in ROIs exceeded the ‘poor’ cut-off of .4, and in fact rarely exceeded .2 (only 4.9%). Motion had a pronounced effect on estimated reliability/stability, with the lowest motion quartile of participants having a mean reliability/stability 2.5 times higher (albeit still ‘poor’) than the highest motion quartile. Poor reliability and stability of task-fMRI, particularly in children, diminishes potential utility of fMRI data due to a drastic reduction of effect sizes and, consequently, statistical power for the detection of brain-behavior associations. This essential issue urgently needs to be addressed through optimization of task design, scanning parameters, data acquisition protocols, preprocessing pipelines, and data denoising methods.

Bayesian interaction selection model for multi-modal neuroimaging data analysis

Zhao Y, Wu B, Kang J. Bayesian interaction selection model for multi-modal neuroimaging data analysis. Biometrics. 2022 Feb 27. doi: 10.1111/biom.13648. Epub ahead of print. PMID: 35220581.

Multi-modality or multi-construct data arise increasingly in functional neuroimaging studies to characterize brain activity under different cognitive states. Relying on those high-resolution imaging collections, it is of great interest to identify predictive imaging markers and inter-modality interactions with respect to behavior outcomes. Currently, most of the existing variable selection models do not consider predictive effects from interactions, and the desired higher-order terms can only be included in the predictive mechanism following a two-step procedure, suffering from potential mis-specification. In this paper, we propose a unified Bayesian prior model to simultaneously identify main effect features and inter-modality interactions within the same inference platform in the presence of high dimensional data. To accommodate the brain topological information and correlation between modalities, our prior is designed by compiling the intermediate selection status of sequential partitions in light of the data structure and brain anatomical architecture, so that we can improve posterior inference and enhance biological plausibility. Through extensive simulations, we show the superiority of our approach in main and interaction effects selection, and prediction under multi-modality data. Applying the method to the Adolescent Brain Cognitive Development (ABCD) study, we characterize the brain functional underpinnings with respect to general cognitive ability under different memory load conditions. This article is protected by copyright. All rights reserved.

Prenatal Selective Serotonin Reuptake Inhibitor Exposure, Depression, and Brain Morphology in Middle Childhood: Results From the ABCD Study

Moreau AL, Voss M, Hansen I, Paul SE, Barch DM, Rogers CE, Bogdan R. (2022, In Press). Prenatal Selective Serotonin Reuptake Inhibitor Exposure, Depression, and Brain Morphology in Middle Childhood: Results From the ABCD Study. Biological Psychiatry, Published: February 26, 2022, DOI:https://doi.org/10.1016/j.bpsgos.2022.02.005

Background
Prenatal selective serotonin reuptake inhibitor (SSRI) exposure has been inconsistently linked to depression, and little is known about neural correlates. We examined whether prenatal SSRI exposure is associated with depressive symptoms and brain structure during middle childhood.

Methods
Prenatal SSRI exposure (retrospective caregiver report), depressive symptoms (caregiver-reported Child Behavior Checklist), and brain structure (magnetic resonance imaging–derived subcortical volume; cortical thickness and surface area) were assessed in children (analytic ns = 5420–7528; 235 with prenatal SSRI exposure; 9–10 years of age) who completed the baseline Adolescent Brain Cognitive Development Study session. Linear mixed-effects models nested data. Covariates included familial, pregnancy, and child variables. Matrix spectral decomposition adjusted for multiple testing.

Results
Prenatal SSRI exposure was not independently associated with depression after accounting for recent maternal depressive symptoms. Prenatal SSRI exposure was associated with greater left superior parietal surface area (b = 145.3 mm2, p = .00038) and lateral occipital cortical thickness (b = 0.0272 mm, p = .0000079); neither was associated with child depressive symptoms. Child depression was associated with smaller global brain structure.

Conclusions
Our findings, combined with adverse outcomes of exposure to maternal depression and the utility of SSRIs for treating depression, suggest that risk for depression during middle childhood should not discourage SSRI use during pregnancy. Associations between prenatal SSRI exposure and brain structure were small in magnitude and not associated with depression. It will be important for future work to examine associations between prenatal SSRI exposure and depression through young adulthood, when risk for depression increases.

Hyperbolic discounting rates and risk for problematic alcohol use in youth enrolled in the Adolescent Brain and Cognitive Development study

Kohler RJ, Lichenstein SD, Yip SW. Hyperbolic discounting rates and risk for problematic alcohol use in youth enrolled in the Adolescent Brain and Cognitive Development study. Addiction Biology, First published: 23 February 2022 https://doi.org/10.1111/adb.13160

Adolescence is the peak period for the emergence of substance use, which can lead to long-term psychosocial, occupational and interpersonal complications. Ongoing large-scale, longitudinal, consortium initiatives, such as the Adolescent Brain and Cognitive Development (ABCD) study, offer unprecedented opportunities to elucidate key risk factors for problematic substance use in a well-powered sample and to examine how changes in risk factors relate to symptoms across time. Delay discounting has been proposed as a putative risk marker for early substance-use initiation and other forms of psychopathology. However, the extent to which other factors (e.g., socio-economic status and cognitive ability) influence discounting behaviour in young adolescents is not well established. The present study leverages data from the ABCD study (n = 11 045) to assess associations between core demographic and familial variables and delay discounting in youth—operationalized using hyperbolic discounting rates (k)—before the onset of significant psychopathology. Model estimates revealed significant effects of individual difference factors (e.g., sex and socio-economic status) and alcohol risk status (based on family history) on delay discounting. No significant differences were observed in the primary sample when comparing the presence of parent drug problems or prenatal drug exposures. These effects will require replication in later waves of ABCD. Nonetheless, these results provide support for delay discounting as a potential risk marker for problematic alcohol use and demonstrate a relationship between key demographic variables and adolescent discounting behaviour. Further, these results provide an empirical baseline from which developmental trajectories of delay discounting and substance use may be tracked throughout future waves of ABCD.

Altered resting fMRI spectral power in data-driven brain networks during development: A longitudinal study

Agcaoglu O, Wilson TW, Wang YP, Stephen JM, Fu Z, Calhoun VD. Altered resting fMRI spectral power in data-driven brain networks during development: A longitudinal study. J Neurosci Methods. 2022 Feb 23;372:109537. doi: 10.1016/j.jneumeth.2022.109537. Epub ahead of print. PMID: 35217109.

Background: Longitudinal studies provide a more precise measure of brain development over time, as they focus on within subject variability, as opposed to cross-sectional studies. This is especially important in children, where rapid brain development occurs, and inter-subject variability can be large. Tracking healthy brain development and identifying markers of typical development are also critically important to diagnose mental disorders at early ages.

New method: We track longitudinal changes in spectral power of time-courses using a unique non-binning approach assessed with group independent component analysis, in a large multi time-point resting state functional magnetic resonance imaging dataset (N = 124) containing healthy children from 8.2 to 17.6 years old (m=12.6) called the Developmental Chronnecto-Genomics study. We examined how eyes open (EO) and eyes closed (EC) resting states play a role in age-related spectral differences, as several studies have reported differences in these conditions.

Results: Typical brain development shows increased spectral power in low frequencies and decreased spectral power in high frequencies in as children grow and develop, for both the EO and EC conditions. In addition, we observed significant differences in power spectra between EO and EC and between sexes, mainly suggesting higher spectral power in females at middle and high frequencies. A replication analysis using the Adolescent Brain Cognitive Development data (N = 3371, mean age 9.9 years old) further supported this result, also showing general increases in low frequencies and decreases in higher frequencies, though some network level differences are present comparing to the main dataset.

Comparison with existing method: Our results indicate that spectral power changes significantly with typical development and our non-binning approach shows these changes with more detailed frequency resolution comparing to binning approaches. This is important as many studies reported an association of higher frequency power with brain disorders.

Conclusion: Our findings of decreased spectral power in the high frequencies with development may be a general marker of typical development., though this needs further investigation.

Exploring neural correlates of behavioral and academic resilience among children in poverty

Ellwood-Lowe ME, Irving CN, Bunge SA. Exploring neural correlates of behavioral and academic resilience among children in poverty. Dev Cogn Neurosci. 2022 Feb 22;54:101090. doi: 10.1016/j.dcn.2022.101090. Epub ahead of print. PMID: 35248821.

Children in poverty must contend with systems that do not meet their needs. We explored what, at a neural level, helps explain children’s resilience in these contexts. Lower coupling between lateral frontoparietal network (LFPN) and default mode network (DMN)-linked, respectively, to externally- and internally-directed thought-has previously been associated with better cognitive performance. However, we recently found the opposite pattern for children in poverty. Here, we probed ecologically-valid assessments of performance. In a pre-registered study, we investigated trajectories of network coupling over ages 9-13 and their relation to school grades and attention problems. We analyzed longitudinal data from ABCD Study (N = 8366 children at baseline; 1303 below poverty). The link between cognitive performance and grades was weaker for children in poverty, highlighting the importance of ecologically-valid measures. As predicted, higher LFPN-DMN connectivity was linked to worse grades and attentional problems for children living above poverty, while children below poverty showed opposite tendencies. This interaction between LFPN-DMN connectivity and poverty related to children’s grades two years later; however, it was attenuated when controlling for baseline grades and was not related to attention longitudinally. Together, these findings suggest network connectivity is differentially related to performance in real-world settings for children above and below poverty.

Clouding up cognition?: Secondhand cannabis and tobacco exposure related to cognitive functioning in youth

Wade NE, McCabe CJ, Wallace AL, Gonzalez MR, Hoh E, Infante M.A, Hernandez Mejia M, Haist F (In Press, 2022). Clouding up cognition?: Secondhand cannabis and tobacco exposure related to cognitive functioning in youth. Biological Psychiatry Global Open Science. Available online 22 February 2022, In Press, Journal Pre-proof, https://doi.org/10.1016/j.bpsgos.2022.01.010

Background
Increasing legalization of cannabis, in addition to longstanding rates of tobacco use, raise concerns for possible cognitive decrements from secondhand smoke or environmental exposure, though little research exists. We investigate the relation between cognition and secondhand and environmental cannabis and tobacco exposure in youth.

Methods
The Adolescent Brain Cognitive Development (ABCD) Study Year 2 Follow-Up (n=5,580; 48% Female) cognitive performance and secondhand or environmental cannabis or tobacco exposure data was used. Principal components analysis identified a global cognition factor. Linear mixed effects models assessed global cognition and individual cognitive task performance by cannabis and/or tobacco environmental exposure. Sociodemographics and other potential confounds were examined. P-values were adjusted using the false-discovery rate method.

Results
Global cognition was not related to any exposure group after testing corrections and considering confounds. Beyond covariates and family/site-level factors, secondhand tobacco was related to poorer visual memory (p=.02), and environmental tobacco was associated with poorer visuospatial (p=.02) and language skills (p=.008). Secondhand cannabis was related to cognition, but not after controlling for potential confounders (p>.05). Environmental cannabis was related to better oral reading (p=.01). Including covariates attenuated effect sizes.

Conclusions
Secondhand tobacco exposure was associated with poorer visual memory, while environmental tobacco exposure was related to poorer language and visuospatial skills. Secondhand cannabis was not related to cognition after controlling for sociodemographic factors, but environmental cannabis exposure was related to better reading. As this is the first known study of its kind and thus preliminary, secondhand cannabis should continue to be investigated to confirm results.

Classifying Conduct Disorder using a biopsychosocial model and machine learning method

Chan L, Simmons C, Tillem S, Conley M, Brazil IA, Baskin-Sommers A. Classifying Conduct Disorder using a biopsychosocial model and machine learning method. Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Feb 22:S2451-9022(22)00043-X. doi: 10.1016/j.bpsc.2022.02.004. Epub ahead of print. PMID: 35217219.

Background: Conduct Disorder (CD) is a common syndrome with far-reaching effects. Risk factors for the development of CD span social, psychological, and biological domains. Researchers note that predictive models of CD are limited if the focus is on a single risk factor or, even, a single domain. Machine learning methods are optimized for the extraction of trends across multi-domain data but have yet to be implemented in predicting the development of CD.

Methods: Social (e.g., family, income), psychological (e.g., psychiatric, neuropsychological), and biological (e.g., resting-state graph metrics) risk factors were measured using data from the baseline visit of the Adolescent Brain Cognitive DevelopmentSM Study when youth were 9-10-years-old (n = 2,368). Applying a feed-forward neural network machine learning method, risk factors were used to predict CD diagnoses two years later.

Results: A model with factors that included social, psychological, and biological domains outperformed models representing factors within any single domain, predicting the presence of a CD diagnosis with 91.18% accuracy. Within each domain, certain factors stood out in terms of their relationship to CD (social: lower parental monitoring, more aggression in the household, lower income; psychological: greater ADHD and ODD symptoms, worse crystallized cognition and card sorting performance; biological: disruptions in the topology of subcortical and frontoparietal networks).

Conclusions: The development of an accurate, sensitive, and specific predictive model of CD has the potential to aid in prevention and intervention efforts. Key risk factors for CD appear best characterized as reflecting unpredictable, impulsive, deprived, and emotional external and internal contexts.

Association of Genome-Wide Polygenic Scores for Multiple Psychiatric and Common Traits in Preadolescent Youths at Risk of Suicide

Yoonie Joo Y, Moon S-Y, Wang H-H, Kim H, Lee E-J, Hun Kim, J, Posner J, Ahn W-Y, Choi I, Kim J-W, Cha J. Association of Genome-Wide Polygenic Scores for Multiple Psychiatric and Common Traits in Preadolescent Youths at Risk of Suicide. JAMA Netw Open. February 21, 2022;5(2):e2148585. doi:10.1001/jamanetworkopen.2021.48585

Importance
Suicide is the second leading cause of death among youths worldwide, but no available means exist to identify the risk of suicide in this population.

Objective
To assess whether genome-wide polygenic scores for psychiatric and common traits are associated with the risk of suicide among preadolescent children and to investigate whether and to what extent the interaction between early life stress (a major environmental risk factor) and polygenic factors is associated with suicidal thoughts and behaviors among youths.

Design, Setting, and Participants
This cohort study analyzed the genotype-phenotype data of 11 869 preadolescent children aged 9 to 10 years from the Adolescent Brain and Cognitive Development study. Data were collected from September 1, 2016, to October 21, 2018, and analyzed from August 1, 2020, to January 3, 2021. Using machine learning approaches, genome-wide polygenic scores of 24 complex traits were estimated to investigate their phenome-wide associations and utility for assessing risk of suicidal thoughts and behaviors (suicidal ideation [active, passive, and overall] and suicide attempt).

Main Outcomes and Measures
Genome-wide polygenic scores were used to measure 24 traits, including psychiatric disorders, cognitive capacity, and personality and psychological characteristics. The Child Behavior Checklist was used to measure early life stress, and the Family Environment Scale was used to assess family environment. Suicidal ideation and suicide attempts were derived from the computerized version of the Kiddie Schedule for Affective Disorders and Schizophrenia.

Results
Among 11 869 preadolescent children in the US, complete data for phenotypic outcomes, genotypes, and covariates were available for 7140 participants in the multiethnic cohort (mean [SD] age, 9.9 [0.6] years; 3588 girls [50.3%]), including 925 participants with suicidal ideation and 63 participants with suicide attempts. Among those 7140 participants, 729 had African ancestry (self-reported race or ethnicity: 569 Black, 71 Hispanic, and 89 other), 276 had admixed American ancestry (self-reported race or ethnicity: 265 Hispanic, 3 White, and 8 other), 150 had East Asian ancestry (self-reported race or ethnicity: 67 Asian, 18 Hispanic, and 65 other), 5718 had European ancestry (self-reported race or ethnicity: 7 Asian, 39 Black, 1142 Hispanic, 3934 White, and 596 other), and 267 had other ancestries (self-reported race or ethnicity: 70 Asian, 13 Black, 126 Hispanic, 48 White, and 10 other). Three genome-wide polygenic scores were significantly associated (false discovery rate P < .05) with suicidal thoughts and behaviors among all participants: attention-deficit/hyperactivity disorder (odds ratio [OR], 1.12; 95% CI, 1.05-1.21; P = .001), schizophrenia (OR, 1.50; 95% CI, 1.17-1.93; P = .002), and general happiness (OR, 0.89; 95% CI, 0.83-0.96; P = .002). In the analysis including only children with European ancestry, 3 additional genome-wide polygenic scores with false discovery rate significance were associated with suicidal thoughts and behaviors: autism spectrum disorder (OR, 1.18; 95% CI, 1.06-1.31; P = .002), major depressive disorder (OR, 1.12; 95% CI, 1.04-1.21; P = .003), and posttraumatic stress disorder (OR, 1.12; 95% CI, 1.04-1.21; P = .004). A significant interaction between genome-wide polygenic scores and environment was found, with genetic risk factors for autism spectrum disorder and the level of early life stress associated with increases in the risk of overall suicidal ideation and overall suicidal thoughts and behaviors (OR, 1.20; 95% CI, 1.07-1.35; P = .002). A machine learning model using multitrait genome-wide polygenic scores and additional self-reported questionnaire data (Child Behavior Checklist and Family Environment Scale) produced a moderately accurate estimate of overall suicidal thoughts and behaviors (area under the receiver operating characteristic curve [AUROC], 0.77; 95% CI, 0.73-0.81; accuracy, 0.67) and suicidal ideation (AUROC, 0.76; 95% CI, 0.72-0.80; accuracy, 0.66) among children with European ancestry only. Among all children in the multiethnic cohort, the integrated model also outperformed the baseline model in estimating the risk of overall suicidal thoughts and behaviors (AUROC, 0.71; 95% CI, 0.67-0.75; accuracy, 0.68) and suicidal ideation (AUROC, 0.75; 95% CI, 0.71-0.78; accuracy, 0.67).

Conclusions and Relevance
In this cohort study of preadolescent youths in the US, higher genome-wide polygenic scores for psychiatric disorders, such as attention-deficit/hyperactivity disorder, autism spectrum disorder, posttraumatic stress disorder, and schizophrenia, were significantly associated with a greater risk of suicidal ideation and suicide attempt. The findings and quantitative models from this study may help to identify children with a high risk of suicide, potentially assisting with early screening, intervention, and prevention.

Companion Animals and Adolescent Stress and Adaptive Coping During the COVID-19 Pandemic

Mueller MK, King EK, Halbreich ED, Callina KS. Companion Animals and Adolescent Stress and Adaptive Coping During the COVID-19 Pandemic. Anthrozoos. 2022;35(5):693-712. doi: 10.1080/08927936.2022.2027093. Epub 2022 Feb 11. PMID: 36387418; PMCID: PMC9662752.

The COVID-19 pandemic has resulted in significant social disruptions for youth caused by lockdowns, school closures, and a lack of in-person social interactions. Companion animals are prevalent in US households and may provide a source of emotional support and motivation for youth to engage in adaptive coping behaviors during social challenges. The goals of this study were to assess if dog owners, non-dog pet owners, and non-pet owners differed in stress levels, positive affect, and use of adaptive coping strategies such as increased time outdoors, regular walking, and healthy behaviors. This study used data collected during the COVID-19 pandemic from the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study, a large, nationally representative dataset of American youth. In a cross-sectional sample of 6,069 adolescents, there were significant, but small, relationships between owning a non-dog pet and lower levels of positive affect, and both dog owners and non-dog pet owners reported higher perceived stress compared with non-pet owners. Dog ownership was associated with higher odds of using healthy coping strategies compared with non-pet owners, but this relationship was not significant when controlling for demographic variables. Dog owners reported higher odds of having a walking routine and spending time outdoors compared with non-pet owners. Overall, the results suggest no buffering effect of pet ownership on youth mental wellbeing, but dog ownership is associated with some healthy coping behaviors linked to walking.

Parent-adolescent agreement in reported moderate-to-vigorous intensity physical activity during the COVID-19 pandemic

Nagata JM, Cortez CA, Iyer P, Dooley EE, Ganson KT, Conroy AA, Gabriel KP. Parent-adolescent agreement in reported moderate-to-vigorous intensity physical activity during the COVID-19 pandemic. BMC Public Health 22, 332 (2022). https://doi.org/10.1186/s12889-022-12530-4

Purpose
To describe the agreement between parent- and adolescent- reports of adolescent moderate-to-vigorous intensity physical activity (MVPA) and to determine sociodemographic factors associated with MVPA reporting differences during the COVID-19 pandemic.

Methods
We analyzed data collected in May 2020 from the Adolescent Brain Cognitive Development Study (ABCD, N = 4841), a U.S. prospective cohort study. We quantified past weekly adolescent MVPA levels as reported by the parent and adolescent (referent). Intra-class correlation coefficients (ICC) and Bland-Altman plots were used to examine the degree of agreement between parent- and adolescent- reports.

Results
When quantifying adolescent MVPA during the same recall period, median (p25, p75) MVPA (h∙wk.− 1) was 2.17 (0.00, 6.00) as reported by adolescents and 1.52 (0.29, 4.75) by parents with a mean difference of 4.89. Statistically significant differences in reports of MVPA were found in households with income > $75,000: on average, adolescents reported higher MVPA levels than their parents. Bland-Altman plots illustrated that, among adolescents reporting no or little MVPA, there was higher parent-adolescent agreement. However, among adolescents reporting high levels of MVPA, there was less agreement between the parent- and adolescent- reports.

Conclusions
Despite more time spent together at home during the pandemic, there was generally low agreement between parent- and adolescent- reports of adolescent MVPA. Future research could examine parent-adolescent agreement of MVPA within the context of device-based measures (e.g., accelerometers), determine reasons for differences in parent-adolescent reporting of MVPA, and inform interventions for improved parental involvement and monitoring of MVPA.

Companion Animals and Adolescent Stress and Adaptive Coping During the COVID-19 Pandemic

Mueller MK, King EK, Halbreich ED, Callina KS. Companion Animals and Adolescent Stress and Adaptive Coping During the COVID-19 Pandemic. Anthrozoös, Published online 11 Feb 2022, https://doi.org/10.1080/08927936.2022.2027093

The COVID-19 pandemic has resulted in significant social disruptions for youth caused by lockdowns, school closures, and a lack of in-person social interactions. Companion animals are prevalent in United States households and may provide a source of emotional support and motivation for youth to engage in adaptive coping behaviors during social challenges. The goals of this study were to assess if dog owners, non-dog pet owners, and non-pet owners differed in stress levels, positive affect, and use of adaptive coping strategies such as increased time outdoors, regular walking, and healthy behaviors. This study used data collected during the COVID-19 pandemic from the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study, a large, nationally representative dataset of American youth. In a cross-sectional sample of 6,069 adolescents, there were significant, but small, relationships between owning a non-dog pet and lower levels of positive affect, and both dog owners and non-dog pet owners reported higher perceived stress compared with non-pet owners. Dog ownership was associated with higher odds of using healthy coping strategies compared with non-pet owners, but this relationship was not significant when controlling for demographic variables. Dog owners reported higher odds of having a walking routine and spending time outdoors compared with non-pet owners. Overall, the results suggest no buffering effect of pet ownership on youth mental wellbeing, but dog ownership is associated with some healthy coping behaviors linked to walking.

Measuring Retention within the Adolescent Brain Cognitive Development (ABCD)SM Study

Feldstein Ewing SW, Dash GF, Thompson WK, Reuter C, Diaz VG, Anokhin A, Chang L, Cottler LB, Dowling GJ, LeBlanc K, Zucker RA, Tapert SF, Brown SA, Garavan H. (2022). Measuring Retention within the Adolescent Brain Cognitive Development (ABCD)SM Study. Developmental Cognitive Neuroscience, Volume 54, April 2022, 101081.

The Adolescent Brain Cognitive Development (ABCD)SM study aims to retain a demographically diverse sample of youth and one parent across 21 sites throughout its 10-year protocol while minimizing selective (systematic) attrition. To evaluate the effectiveness of these efforts, the ABCD Retention Workgroup (RW) has employed a data-driven approach to examine, track, and intervene via three key metrics: (1) which youth completed visits late; (2) which youth missed visits; (3) which youth withdrew from the study. The RW actively examines demographic (race, education level, family income) and site factors (visit satisfaction, distance from site, and enrollment in ancillary studies) to strategize efforts that will minimize disengagement and loss of participating youth and parents. Data showed that the most robust primary correlates of late visits were distance from study site, race, and parental education level. Race, lower parental education level, parental employment status, and lower family income were associated with higher odds of missed visits, while being enrolled in one of the ancillary studies was associated with lower odds of missed visits. Additionally, it appeared that parents who were primary Spanish speakers withdrew at slightly higher rates. These findings provide insight into future targets for proactive retention efforts by the ABCD RW.

Multivariate, Transgenerational Associations of the COVID-19 Pandemic Across Minoritized and Marginalized Communities

Yip SW, Jordan A, Kohler RJ, Holmes A, Bzdok D. Multivariate, Transgenerational Associations of the COVID-19 Pandemic Across Minoritized and Marginalized Communities. JAMA Psychiatry. Published online February 9, 2022. doi:10.1001/jamapsychiatry.2021.4331

Importance
The experienced consequences of the COVID-19 pandemic have diverged across individuals, families, and communities, resulting in inequity within a host of factors. There is a gap of quantitative evidence about the transgenerational impacts of these experiences and factors.

Objective
To identify baseline predictors of COVID-19 experiences, as defined by child and parent report, using a multivariate pattern-learning framework from the Adolescent Brain and Cognitive Development (ABCD) cohort.

Design, Setting, and Participants
ABCD is an ongoing prospective longitudinal study of child and adolescent development in the United States including 11 875 youths, enrolled at age 9 to 10 years. Using nationally collected longitudinal profiling data from 9267 families, a multivariate pattern-learning strategy was developed to identify factor combinations associated with transgenerational costs of the ongoing COVID-19 pandemic. ABCD data (release 3.0) collected from 2016 to 2020 and released between 2019 and 2021 were analyzed in combination with ABCD COVID-19 rapid response data from the first 3 collection points (May-August 2020).

Exposures
Social distancing and other response measures imposed by COVID-19, including school closures and shutdown of many childhood recreational activities.

Main Outcomes and Measures
Mid–COVID-19 experiences as defined by the ABCD’s parent and child COVID-19 assessments.

Results
Deep profiles from 9267 youth (5681 female [47.8%]; mean [SD] age, 119.0 [7.5] months) and their caregivers were quantitatively examined. Enabled by a pattern-learning analysis, social determinants of inequity, including family structure, socioeconomic status, and the experience of racism, were found to be primarily associated with transgenerational impacts of COVID-19, above and beyond other candidate predictors such as preexisting medical or psychiatric conditions. Pooling information across more than 17 000 baseline pre–COVID-19 family indicators and more than 280 measures of day-to-day COVID-19 experiences, non-White (ie, families who reported being Asian, Black, Hispanic, other, or a combination of those choices) and/or Spanish-speaking families were found to have decreased resources (mode 1, canonical vector weight [CVW] = 0.19; rank 5 of 281), escalated likelihoods of financial worry (mode 1, CVW = −0.20; rank 4), and food insecurity (mode 1, CVW = 0.21; rank 2), yet were more likely to have parent-child discussions regarding COVID-19–associated health and prevention issues, such as handwashing (mode 1, CVW = 0.14; rank 9), conserving food or other items (mode 1, CVW = 0.21; rank 1), protecting elderly individuals (mode 1, CVW = 0.11; rank 21), and isolating from others (mode 1, CVW = 0.11; rank 23). In contrast, White families (mode 1, CVW = −0.07; rank 3), those with higher pre–COVID-19 income (mode 1, CVW = −0.07; rank 5), and presence of a parent with a postgraduate degree (mode 1, CVW = −0.06; rank 14) experienced reduced COVID-19–associated impact. In turn, children from families experiencing reduced COVID-19 impacts reported longer nighttime sleep durations (mode 1, CVW = 0.13; rank 14), less difficulties with remote learning (mode 2, CVW = 0.14; rank 7), and decreased worry about the impact of COVID-19 on their family’s financial stability (mode 1, CVW = 0.134; rank 13).

Conclusions and Relevance
The findings of this study indicate that community-level, transgenerational intervention strategies may be needed to combat the disproportionate burden of pandemics on minoritized and marginalized racial and ethnic populations.

Causal effects of psychostimulants on neural connectivity: a mechanistic, randomized clinical trial

Wang Y, Kessel E, Lee S, Hong S, Raffanello E, Hulvershorn LA, Margolis A, Peterson BS, Posner, J. Causal effects of psychostimulants on neural connectivity: a mechanistic, randomized clinical trial. The Journal of Child Psychology and Psychiatry, 09 Feb 2022, https://doi.org/10.1111/jcpp.13585.

Background
Psychostimulants are frequently used to treat attention-deficit/hyperactivity disorder (ADHD), but side effects are common leading to many patients discontinuing treatment. Identifying neural mechanisms by which psychostimulants attenuate symptoms may guide the development of more refined and tolerable therapeutics.

Methods
We conducted a 12-week, randomized, placebo-controlled trial (RCT) of a long-acting amphetamine, lisdexamfetamine (LDEX), in patients with ADHD, ages 6–25 years old. Of the 58 participants who participated in the RCT, 49 completed pre- and post-RCT magnetic resonance imaging scanning with adequate data quality. Healthy controls (HCs; n = 46) were included for comparison. Treatment effects on striatal and thalamic functional connectivity (FC) were identified using static (time-averaged) and dynamic (time-varying) measures and then correlated with symptom improvement. Analyses were repeated in independent samples from the Adolescent Brain Cognitive Development study (n = 103) and the ADHD-200 Consortium (n = 213).

Results
In 49 participants (25 LDEX; 24 Placebo), LDEX increased static and decreased dynamic FC (DFC). However, only DFC was associated with the therapeutic effects of LDEX. Additionally, at baseline, DFC was elevated in unmedicated-ADHD participants relative to HCs. Independent samples yielded similar findings – ADHD was associated with increased DFC, and psychostimulants with reduced DFC. Static FC findings were inconsistent across samples.

Conclusions
Changes in dynamic, but not static, FC were associated with the therapeutic effects of psychostimulants. While prior research has focused on static FC, DFC may offer a more reliable target for new ADHD interventions aimed at stabilizing network dynamics, though this needs confirmation with subsequent investigations.

Resilience to COVID-19: Socioeconomic Disadvantage Associated With Positive Caregiver–Youth Communication and Youth Preventative Actions

Marshall AT, Hackman DA, Baker FC, Breslin FJ, Brown SA, Dick AS, Gonzalez MR, Guillaume M, Kiss O, Lisdahl KM, McCabe CJ, Pelham III WE, Sheth C, Tapert SF, Van Rinsveld A, Wade NE, Sowell ER. Resilience to COVID-19: Socioeconomic Disadvantage Associated With Positive Caregiver–Youth Communication and Youth Preventative Actions. Front. Public Health, 09 February 2022 | https://doi.org/10.3389/fpubh.2022.734308

Socioeconomic disadvantage is associated with larger COVID-19 disease burdens and pandemic-related economic impacts. We utilized the longitudinal Adolescent Brain Cognitive Development Study to understand how family- and neighborhood-level socioeconomic disadvantage relate to disease burden, family communication, and preventative responses to the pandemic in over 6,000 youth-caregiver dyads. Data were collected at three timepoints (May–August 2020). Here, we show that both family- and neighborhood-level disadvantage were associated with caregivers’ reports of greater family COVID-19 disease burden, less perceived exposure risk, more frequent caregiver-youth conversations about COVID-19 risk/prevention and reassurance, and greater youth preventative behaviors. Families with more socioeconomic disadvantage may be adaptively incorporating more protective strategies to reduce emotional distress and likelihood of COVID-19 infection. The results highlight the importance of caregiver-youth communication and disease-preventative practices for buffering the economic and disease burdens of COVID-19, along with policies and programs that reduce these burdens for families with socioeconomic disadvantage.

Classification of suicidal thoughts and behaviour in children: results from penalised logistic regression analyses in the Adolescent Brain Cognitive Development study

van Velzen LS, Toenders YJ, Avila-Parcet A, Dinga R, Rabinowitz JA, Campos AI, Jahanshad N, Rentería ME, Schmaal L. Classification of suicidal thoughts and behaviour in children: results from penalised logistic regression analyses in the Adolescent Brain Cognitive Development study. Br J Psychiatry. 2022 Feb 9:1-9. doi: 10.1192/bjp.2022.7. Epub ahead of print. PMID: 35135639.

Background: Despite efforts to predict suicide risk in children, the ability to reliably identify who will engage in suicide thoughts or behaviours has remained unsuccessful.

Aims: We apply a novel machine-learning approach and examine whether children with suicide thoughts or behaviours could be differentiated from children without suicide thoughts or behaviours based on a combination of traditional (sociodemographic, physical health, social-environmental, clinical psychiatric) risk factors, but also more novel risk factors (cognitive, neuroimaging and genetic characteristics).

Method: The study included 5885 unrelated children (50% female, 67% White, 9-11 years of age) from the Adolescent Brain Cognitive Development (ABCD) study. We performed penalised logistic regression analysis to distinguish between: (a) children with current or past suicide thoughts or behaviours; (b) children with a mental illness but no suicide thoughts or behaviours (clinical controls); and (c) healthy control children (no suicide thoughts or behaviours and no history of mental illness). The model was subsequently validated with data from seven independent sites involved in the ABCD study (n = 1712).

Results: Our results showed that we were able to distinguish the suicide thoughts or behaviours group from healthy controls (area under the receiver operating characteristics curve: 0.80 child-report, 0.81 for parent-report) and clinical controls (0.71 child-report and 0.76-0.77 parent-report). However, we could not distinguish children with suicidal ideation from those who attempted suicide (AUROC: 0.55-0.58 child-report; 0.49-0.53 parent-report). The factors that differentiated the suicide thoughts or behaviours group from the clinical control group included family conflict, prodromal psychosis symptoms, impulsivity, depression severity and history of mental health treatment.

Conclusions: This work highlights that mostly clinical psychiatric factors were able to distinguish children with suicide thoughts or behaviours from children without suicide thoughts or behaviours. Future research is needed to determine if these variables prospectively predict subsequent suicidal behaviour.

Associations between social behaviors and experiences with neural correlates of implicit emotion regulation in middle childhood

Geckeler KC, Barch DM, Karcher NR. Associations between social behaviors and experiences with neural correlates of implicit emotion regulation in middle childhood. Neuropsychopharmacology. 2022 Feb 8. doi: 10.1038/s41386-022-01286-5. Epub ahead of print. PMID: 35136189.

Emotion regulation is essential for successful social interactions and function, which are important aspects of middle childhood. The current study is one of the first to examine associations between neural correlates of implicit emotion regulation and indices of social behavior and experience during late middle childhood. We examined neural activation during the implicit emotion regulation condition of the Emotional N-back task using data from 8987 9- to 11-year-olds from the Adolescent Brain Cognitive Development℠ study. The brain regions assessed included areas linked to social cognition, social behavior, and emotion recognition, including the amygdala, insula, middle temporal gyrus, and inferior parietal lobe. Greater number of close friends was associated with significantly higher activation of the fusiform gyrus, insula, temporoparietal junction, inferior parietal lobe, and superior temporal gyrus during implicit emotion regulation. Greater reciprocal social impairments were linked to decreased fusiform gyrus activation during implicit emotion regulation. More experiences of discrimination were associated with a significantly lower activation in the middle temporal gyrus during implicit emotion regulation. This study provides evidence that both positive and negative indices of children’s social experiences and behaviors are associated with neural correlates of implicit emotion regulation during late middle childhood. These findings suggest that both positive and negative indices of social behavior and experience, including those within and not within the youth’s control, are associated with generally unique neural correlates during implicit emotion regulation.

Associations between potentially traumatic events and psychopathology among preadolescents in the Adolescent Brain and Cognitive Development Study®

Thompson EL, Lever NA, Connors KM, Cloak CC, Reeves G, Chang L. Associations between potentially traumatic events and psychopathology among preadolescents in the Adolescent Brain and Cognitive Development Study®. J Trauma Stress. 2022 Feb 8. doi: 10.1002/jts.22793. Epub ahead of print. PMID: 35132700.

The current cross-sectional study aimed to extend the literature on childhood adversity by examining the unique associations between potentially traumatic events (PTEs) and a range of mental health concerns, including domain-specific versus comorbid concerns. Participants were 11,877 preadolescents (47.8% female, 15.0% Black, 20.3% Hispanic/Latinx, Mage = 9.5 years) taking part in the Adolescent Brain and Cognitive Development (ABCD) Study® . The Kiddie Schedule for Affective Disorders and Schizophrenia was used to measure PTEs and caregiver- and child-reported mental health concerns. Adjusted odds ratios (aORs) were used for the outcomes of interest. Overall, PTEs were consistently associated with increased odds of experiencing comorbid posttraumatic stress disorder (PTSD), internalizing disorders, and externalizing disorders, significant AORs = 1.34-4.30, after accounting for children’s experiences of other PTEs and polyvictimization. In contrast, PTEs were generally not associated with meeting the criteria for diagnoses within only one domain (i.e., internalizing-only or externalizing-only diagnoses). We also found PTEs to be differentially related to the various mental health outcomes. In particular, witnessing domestic violence was consistently associated with children’s psychopathology. Other PTEs, such as witnessing community violence, were not associated with children’s psychopathology in the final model. Associations between PTEs and mental health concerns did not differ as a function of sex. Overall, the results support the notion that PTEs are associated with comorbid concerns rather than individual disorders. These findings have important implications for the screening of PTEs, continued research on the conceptualization of traumatic stress, and the importance of accounting for comorbidities across mental health domains.

Parental Arrest and Child Behavior: Differential Role of Executive Functioning among Racial Subgroups

Johnson, E.I., Planalp, E.M. & Poehlmann-Tynan, J. Parental Arrest and Child Behavior: Differential Role of Executive Functioning among Racial Subgroups. J Child Fam Stud (2022). https://doi.org/10.1007/s10826-022-02251-y

This study examines relations among parental arrest, child executive functioning (EF), and problem behaviors among youth who participated in the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) study (N = 11,875). Participants ranged in age from 9 to 10 (M = 9.91) years, and approximately half were girls (47.9%). Results of regression analyses that controlled for sociodemographic risk factors indicated that children who experienced parental arrest exhibited more internalizing and externalizing behaviors than comparison youth, particularly when their mother vs. father had been arrested. Results of analyses that were disaggregated by child race further revealed that EF appeared to play a differential role among White (n = 5851) and Black (n = 1451) children. Among White children, EF was associated with fewer internalizing and externalizing behaviors regardless of whether or not a parent had been arrested. Among Black children, low levels of EF were associated with more internalizing behaviors in the context of parental arrest vs. no arrest, but high levels of EF did not appear to confer benefits. EF was not significantly related to externalizing behaviors among Black children. Taken together, results suggest that parental arrests have adverse implications for child well-being that warrant continued theoretical and empirical attention. Findings also suggest that, although EF may be broadly beneficial among White children, there appear to be constraints on the extent to which high EF benefits Black children, a finding that is discussed through the lens of racial stratification and that has important implications for future theory, research, and practice.

Structural brain measures among children with and without ADHD in the Adolescent Brain and Cognitive Development Study cohort: a cross-sectional US population-based study

Bernanke J, Luna A, Chang l, Bruno E, Dworkin J, Posner J (2022). Structural brain measures among children with and without ADHD in the Adolescent Brain and Cognitive Development Study cohort: a cross-sectional US population-based study, The Lancet Psychiatry, Feb 7, 2022, DOI:https://doi.org/10.1016/S2215-0366(21)00505-8.

Background
Structural neuroimaging research has identified a variety of abnormalities in cortical and subcortical structures in children with ADHD. However, studies to date have not employed large, non-referred samples, complete with data on potential confounding variables. Here, we tested for differences in structural MRI measures among children with and without ADHD using data from the Adolescent Brain and Cognitive Development (ABCD) Study, the largest paediatric brain imaging study in the USA.

Methods
In this cross-sectional study, we used baseline demographic, clinical, and neuroimaging data from the ABCD Study, which recruited children aged 9–10 years between Sept 1, 2016, and Aug 31, 2018, representative of the sociodemographic features of the US population. ADHD was diagnosed by parent report of symptoms. Neuroimaging data underwent centralised quality control and processing by the ABCD team. Linear mixed effects models were used to estimate Cohen’s d values associated with ADHD for 79 brain measures of cortical thickness, cortical area, and subcortical volume. We used a novel simulation strategy to assess the ability to detect significant effects despite potential diagnostic misclassification.

Findings
Our sample included 10 736 participants (5592 boys, 5139 girls; 5692 White, 2165 Hispanic, 1543 Black, 221 Asian, and 1100 of other race or ethnicity), of whom, 949 met the criteria for ADHD and 9787 did not. In the full model, which included potential confounding variables selected a priori, we found only 11 significant differences across the 79 brain measures after false discovery rate correction, all indicating reductions in brain measures among participants with ADHD. Cohen’s d values were small, ranging from −0·11 to −0·06, and were not meaningfully changed by using a more restrictive comparison group or alternative diagnostic methods. Simulations indicated adequate statistical power to detect differences even if there was substantial diagnostic misclassification.

Interpretation
In a sample representative of the general population, children aged 9–10 years with ADHD differed only modestly on structural brain measures from their unaffected peers. Future studies might need to incorporate other MRI modalities, novel statistical approaches, or alternative diagnostic classifications, particularly for research aimed at developing ADHD diagnostic biomarkers.

Discovery of genomic loci of the human cerebral cortex using genetically informed brain atlases

Makowski C, Van Der Meer D, Dong W, Wang H, Wu Y, Zou J, Liu C, Rosenthal SB, Hagler Jr., Fan CC, Kremen WS, Andreassen OA, Jernigan TL, Dale AM, Zhang K, Visscher PM, Yang J, Chen C. DJ. Discovery of genomic loci of the human cerebral cortex using genetically informed brain atlases. Science, Feb 3, 2022, Vol 375, Issue 6580, pp. 522-528, DOI: 10.1126/science.abe8457

To determine the impact of genetic variants on the brain, we used genetically informed brain atlases in genome-wide association studies of regional cortical surface area and thickness in 39,898 adults and 9136 children. We uncovered 440 genome-wide significant loci in the discovery cohort and 800 from a post hoc combined meta-analysis. Loci in adulthood were largely captured in childhood, showing signatures of negative selection, and were linked to early neurodevelopment and pathways associated with neuropsychiatric risk. Opposing gradations of decreased surface area and increased thickness were associated with common inversion polymorphisms. Inferior frontal regions, encompassing Broca’s area, which is important for speech, were enriched for human-specific genomic elements. Thus, a mixed genetic landscape of conserved and human-specific features is concordant with brain hierarchy and morphogenetic gradients.

Age-related changes and longitudinal stability of individual differences in ABCD Neurocognition measures

Anokhin AP, Luciana M, Banich M, Barch D, Bjork JM, Gonzalez MR, Gonzalez R, Haist F, Jacobus J, Lisdahl K, McGlade E, McCandliss B, Nagel B, Nixon SJ, Tapert S, Kennedy JT, Thompson W (2022). Age-related changes and longitudinal stability of individual differences in ABCD Neurocognition measures. Developmental Cognitive Neuroscience. Volume 54, April 2022, 101078

Temporal stability of individual differences is an important prerequisite for accurate tracking of prospective relationships between neurocognition and real-world behavioral outcomes such as substance abuse and psychopathology. Here we report age-related changes and longitudinal test-retest stability (TRS) for the Neurocognition battery of the Adolescent Brain and Cognitive Development (ABCD) study, which included the NIH Toolbox (TB) Cognitive Domain and additional memory and visuospatial processing tests administered at baseline (ages 9–11) and two-year follow-up. As expected, performance improved significantly with age, but the effect size varied broadly, with Pattern Comparison and the Crystallized Cognition Composite showing the largest age-related gain (Cohen’s d:.99 and.97, respectively). TRS ranged from fair (Flanker test: r = 0.44) to excellent (Crystallized Cognition Composite: r = 0.82). A comparison of longitudinal changes and cross-sectional age-related differences within baseline and follow-up assessments suggested that, for some measures, longitudinal changes may be confounded by practice effects and differences in task stimuli or procedure between baseline and follow-up. In conclusion, a subset of measures showed good stability of individual differences despite significant age-related changes, warranting their use as prospective predictors. However, caution is needed in the interpretation of observed longitudinal changes as indicators of neurocognitive development.

The role of school environment in brain structure, connectivity, and mental health in children – a multi-modal investigation

Rakesh D, Zalesky A, Whittle S. The role of school environment in brain structure, connectivity, and mental health in children – a multi-modal investigation. Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Feb 2:S2451-9022(22)00023-4. doi: 10.1016/j.bpsc.2022.01.006. Epub ahead of print. PMID: 35123109.

Background: Much work has been dedicated to understanding the effects of adverse home environments on brain development. While the school social and learning environment plays a role in child development, little work has been done to investigate the impact of the school environment on the developing brain. The goal of the present study was to examine associations between the school environment, brain structure and connectivity, and mental health.

Methods: In this preregistered study we investigated these questions in a large sample of adolescents (9-10 years) from the Adolescent Brain Cognitive Development (ABCD) Study. We examined the association between school environment and gray (N = 10,435). and white matter (N= 10,770) structure and functional connectivity (N = 9,528). We then investigated multivariate relationships between school-associated brain measures and mental health.

Results: School environment was associated with connectivity of the auditory and retrosplenial temporal network as well as of higher-order cognitive networks like the cingulo-opercular, default mode, ventral attention, and frontoparietal networks. Multivariate analyses revealed that connectivity of cingulo-opercular and default mode networks were also associated with mental health.

Conclusions: Findings shed light on the neural mechanisms through which favorable school environments may contribute to positive mental health outcomes in children. Our findings have implications for interventions targeted at promoting positive youth functioning through improving school environments.

Spatio-Temporal Directed Acyclic Graph Learning with Attention Mechanisms on Brain Functional Time Series and Connectivity

Huang S-G, Xia J, Xu L, Qiu A. (2022). Spatio-Temporal Directed Acyclic Graph Learning with Attention Mechanisms on Brain Functional Time Series and Connectivity. Medical Image Analysis, Volume 77, April 2022, 102370.

We develop a deep learning framework, spatio-temporal directed acyclic graph with attention mechanisms (ST-DAG-Att), to predict cognition and disease using functional magnetic resonance imaging (fMRI). This ST-DAG-Att framework comprises of two neural networks, 1) spatio-temporal graph convolutional network (ST-graph-conv) to learn the spatial and temporal information of functional time series at multiple temporal and spatial graph scales, where the graph is represented by the brain functional network, the spatial convolution is over the space of this graph, and the temporal convolution is over the time dimension; 2) functional connectivity convolutional network (FC-conv) to learn functional connectivity features, where the functional connectivity is derived from embedded multi-scale fMRI time series and the convolutional operation is applied along both edge and node dimensions of the brain functional network. This framework also consists of an attention component, i.e., functional connectivity-based spatial attention (FC-SAtt), that generates a spatial attention map through learning the local dependency among high-level features of functional connectivity and emphasizing meaningful brain regions. Moreover, both the ST-graph-conv and FC-conv networks are designed as feed-forward models structured as directed acyclic graphs (DAGs). Our experiments employ two large-scale datasets, Adolescent Brain Cognitive Development (ABCD, n=7693) and Open Access Series of Imaging Study-3 (OASIS-3, n=1786). Our results show that the ST-DAG-Att model is generalizable from cognition prediction to age prediction. It is robust to independent samples obtained from different sites of the ABCD study. It outperforms the existing machine learning techniques, including support vector regression (SVR), elastic net’s mixture with random forest, spatio-temporal graph convolution, and BrainNetCNN.

Erratum to: Morphology of the prefrontal cortex predicts body composition in early adolescence: cognitive mediators and environmental moderators in the ABCD Study

Hall PA, Best JR, Beaton EA, Sakib MN, Danckert J. Erratum to: Morphology of the prefrontal cortex predicts body composition in early adolescence: cognitive mediators and environmental moderators in the ABCD Study. Soc Cogn Affect Neurosci. 2022 Jan 29:nsac002. doi: 10.1093/scan/nsac002. Epub ahead of print. Erratum for: Soc Cogn Affect Neurosci. 2021 Sep 02;: PMID: 35104344.

Associations among Household and Neighborhood Socioeconomic Disadvantages, Resting-state Frontoamygdala Connectivity, and Internalizing Symptoms in Youth

Ip KI, Sisk LM, Horien C, Conley MI, Rapuano KM, Rosenberg MD, Greene AS, Scheinost D, Constable RT, Casey BJ, Baskin-Sommers A, Gee DG. Associations among Household and Neighborhood Socioeconomic Disadvantages, Resting-state Frontoamygdala Connectivity, and Internalizing Symptoms in Youth. J Cogn Neurosci. 2022 Jan 28:1-32. doi: 10.1162/jocn_a_01826. Epub ahead of print. PMID: 35104356.

Exposure to socioeconomic disadvantages (SED) can have negative impacts on mental health, yet SED are a multifaceted construct and the precise processes by which SED confer deleterious effects are less clear. Using a large and diverse sample of preadolescents (ages 9-10 years at baseline, n = 4038, 49% female) from the Adolescent Brain Cognitive Development Study, we examined associations among SED at both household (i.e., income-needs and material hardship) and neighborhood (i.e., area deprivation and neighborhood unsafety) levels, frontoamygdala resting-state functional connectivity, and internalizing symptoms at baseline and 1-year follow-up. SED were positively associated with internalizing symptoms at baseline and indirectly predicted symptoms 1 year later through elevated symptoms at baseline. At the household level, youth in households characterized by higher disadvantage (i.e., lower income-to-needs ratio) exhibited more strongly negative frontoamygdala coupling, particularly between the bilateral amygdala and medial OFC (mOFC) regions within the frontoparietal network. Although more strongly positive amygdala-mOFC coupling was associated with higher levels of internalizing symptoms at baseline and 1-year follow-up, it did not mediate the association between income-to-needs ratio and internalizing symptoms. However, at the neighborhood level, amygdala-mOFC functional coupling moderated the effect of neighborhood deprivation on internalizing symptoms. Specifically, higher neighborhood deprivation was associated with higher internalizing symptoms for youth with more strongly positive connectivity, but not for youth with more strongly negative connectivity, suggesting a potential buffering effect. Findings highlight the importance of capturing multilevel socioecological contexts in which youth develop to identify youth who are most likely to benefit from early interventions.

Birth Weight and Childhood Psychopathology in the ABCD Cohort: Association is Strongest for Attention Problems and is Moderated by Sex

Dooley N, Clarke M, Cotter D, Cannon M. Birth Weight and Childhood Psychopathology in the ABCD Cohort: Association is Strongest for Attention Problems and is Moderated by Sex. Res Child Adolesc Psychopathol. 2022 Jan 24. doi: 10.1007/s10802-021-00859-0. Epub ahead of print. PMID: 35072847.

Many studies have shown low birth weight is associated with psychopathology later in life, particularly attention-deficit/hyperactivity disorder (ADHD). The association is well-replicated, independent from a variety of potential familial confounds, and follows a dose-response curve (decreasing birth weight linked with increasing odds of disorder). However, the specificity of the association to attention problems is called into question by the extent of comorbidity in ADHD, and recent findings that the association is stronger for autism than ADHD. We test the relative dose-response strength of birth weight on multiple aspects of behavior to explore specificity of the effect to attention problems. We also test recent suggestions that the association between birth weight and attention problems is driven by males. Our sample consisted of 9,076 children aged 9-10 from the United States (Adolescent Brain Cognitive Development study). Outcomes included 9 problem-scales and the total problems scale from the Child Behavior Checklist (CBCL). Attention problems were the most strongly associated with birth weight after controlling for gestational age, potential familial confounds, and multiple testing, supporting the outcome-specificity of this association. Contrary to recent registry-based findings, an association between birth weight and an autism scale was not observed. Sex moderated the effect of birth weight on total problems, attention problems and aggressive behavior such that these inverse associations were strongly driven by males. Our findings have strong implications for sex-specific prediction and etiological models of childhood psychopathology.

Socioeconomic status, BMI, and brain development in children

Dennis E, Manza P, Volkow ND. Socioeconomic status, BMI, and brain development in children. Transl Psychiatry. 2022 Jan 24;12(1):33. doi: 10.1038/s41398-022-01779-3. PMID: 35075111.

Low socioeconomic status (SES) in childhood is associated with deficits in executive function and changes in cortical morphology. Furthermore, rates of childhood obesity are greater among low SES children and childhood obesity is also associated with cortical alterations and impaired neurocognition, specifically in the domain of executive function. To investigate the influence of BMI on the relationships between SES and both neurocognition and brain morphology, we used data from the Adolescent Brain Cognitive Development (ABCD) study to construct multiple linear regression models and conduct mediation analyses. Overall, SES as measured by household income, highest level of parental education, and area deprivation, was associated with lower BMI, greater total and prefrontal cortical volume, and better performance on assessments of executive function. Mediation analysis indicated that BMI had a significant indirect effect on associations between area deprivation and both total and prefrontal cortical volumes. BMI also played a mediating role in the associations between area deprivation and composite neurocognitive scores, which were driven by performance on tasks of working memory and cognitive flexibility, but not cognitive control. These findings suggest that BMI should be considered in future studies investigating the relationship between low SES and poor neurodevelopmental outcomes.

Stability of polygenic scores across discovery genome-wide association studies

Schultz LM, Merikangas AK, Ruparel K, Jacquemont S, Glahn DC, Gur RE, Barzilay R, Almasy L. Stability of polygenic scores across discovery genome-wide association studies. HGG Adv. 2022 Jan 21;3(2):100091. doi: 10.1016/j.xhgg.2022.100091. PMID: 35199043; PMCID: PMC8841810.

Polygenic scores (PGS) are commonly evaluated in terms of their predictive accuracy at the population level by the proportion of phenotypic variance they explain. To be useful for precision medicine applications, they also need to be evaluated at the individual level when phenotypes are not necessarily already known. We investigated the stability of PGS in European American (EUR) and African American (AFR)-ancestry individuals from the Philadelphia Neurodevelopmental Cohort and the Adolescent Brain Cognitive Development study using different discovery genome-wide association study (GWAS) results for post-traumatic stress disorder (PTSD), type 2 diabetes (T2D), and height. We found that pairs of EUR-ancestry GWAS for the same trait had genetic correlations >0.92. However, PGS calculated from pairs of same-ancestry and different-ancestry GWAS had correlations that ranged from <0.01 to 0.74. PGS stability was greater for height than for PTSD or T2D. A series of height GWAS in the UK Biobank suggested that correlation between PGS is strongly dependent on the extent of sample overlap between the discovery GWAS. Focusing on the upper end of the PGS distribution, different discovery GWAS do not consistently identify the same individuals in the upper quantiles, with the best case being 60% of individuals above the 80th percentile of PGS overlapping from one height GWAS to another. The degree of overlap decreases sharply as higher quantiles, less heritable traits, and different-ancestry GWAS are considered. PGS computed from different discovery GWAS have only modest correlation at the individual level, underscoring the need to proceed cautiously with integrating PGS into precision medicine applications.

Psychiatric comorbidity associated with weight status in 9 to 10 year old children

Smith KE, Mason TB. Psychiatric comorbidity associated with weight status in 9 to 10 year old children. Pediatr Obes. 2022 Jan 19:e12883. doi: 10.1111/ijpo.12883. Epub ahead of print. PMID: 35048539.

Background: Paediatric overweight and obesity (OW/OB) constitute a serious public health concern. Given that psychological problems may be key contributors to the onset and maintenance of paediatric obesity, the present study examined past and current psychiatric comorbidities across the weight spectrum during middle childhood among a nationally representative sample.

Methods: Participants were 11 708 9- to 10-year-old children (31.6% with OW/OB) and their caregivers who participated in the first wave of data collection in the Adolescent Brain Cognitive Development (ABCD) study. Logistic regressions were used to examine the association between weight status (i.e., underweight, healthy weight, OW, OB) and likelihood of current/past psychiatric diagnoses.

Results: Compared to healthy weight children, those with OW/OB were more likely to have current/past major depressive disorder and binge eating disorder. Relative to healthy weight children, those with OB were more likely to have prior separation anxiety disorder, current specific phobia and oppositional defiant disorder; those with OW were more likely to have PTSD; and those with underweight were more likely to have ADHD.

Conclusions: Results suggest cross-sectional associations among negative emotionality, binge eating, and OW/OB, and highlight the need for ongoing prospective research to investigate directionality of associations and mechanisms of effects.

Transforming the Future of Adolescent Health: Opportunities From the Adolescent Brain Cognitive Development Study

Hoffman EA, LeBlanc K, Weiss SRB, Dowling GJ. Transforming the Future of Adolescent Health: Opportunities From the Adolescent Brain Cognitive Development Study. Journal of Adolescent Health, Vol 70, Issue 2, P186-188, February 01, 2022, DOI:https://doi.org/10.1016/j.jadohealth.2021.11.008

Adolescence is a period of dramatic expansion of the knowledge and skills critical for transitioning into adulthood. Yet, there is much to learn about how adolescent experiences affect brain, cognitive, social, and emotional development. Over the last decade, evidence has revealed associations between early life adversity (e.g., poverty) and later changes in brain structure and function. More recently, research has shown that positive factors (e.g., perceived social supports, increased access to community resources) are associated with healthier development, even for children living in deep poverty, suggesting that protective factors may mitigate the possible negative influences of adverse experiences on health and development . Looking into the next decade, important forces (e.g., digital media, racial inequities, climate change, long-term impacts of COVID-19) will affect adolescent health and well-being globally. Our imperative is to harness advances in science and technology to develop strategies that will enhance health and promote equity.

Conclusion: The diversity of the ABCD cohort, the breadth of data collected, and the longitudinal design of ABCD will provide opportunities for investigating the interplay of environments and experiences with long-term health outcomes. These data have the potential to facilitate the development of strategies for enhancing adolescent health and equity for generations to come.

Motor abnormalities, depression risk, and clinical course in adolescence

Damme KSF, Park JS, Vargas T, Walther S, Shankman SA, Mittal VA. Motor abnormalities, depression risk, and clinical course in adolescence, Biological Psychiatry Global Open Science, Volume 2, Issue 1, January 2022, Pages 61-69, ISSN 2667-1743, https://doi.org/10.1016/j.bpsgos.2021.06.011.

Background
Motor abnormalities, such as psychomotor agitation and retardation, are widely recognized as core features of depression. However, it is not currently known if motor abnormalities connote risk for depression.

Methods
Using data from the Adolescent Brain Cognitive Development (ABCD) Study, a nationally representative sample of youth (n=10,835, 9–11 years old), the present paper examines whether motor abnormalities are associated with (a) depression symptoms in early adolescence, (b) familial risk for depression (familial risk loading), and (c) future depression symptoms. Motor abnormalities measures included traditional (DSM) motor signs such as psychomotor agitation and retardation as well as other motor domains such as developmental motor delays and dyscoordination.

Results
Traditional motor abnormalities were less prevalent (agitation=3.2%, retardation=0.3%) than non-traditional domains (delays=13.79%, coordination=35.5%) among adolescents. Motor dysfunction was associated with depression symptoms (Cohen’s ds=0.02 to 0.12). Familial risk for depression was related to motor abnormalities (Cohen’s ds=0.08 to 0.27), with the exception of motor retardation. Family vulnerability varied in sensitivity to depression risk (e.g., retardation: .53%; dyscoordination: 32.05%). Baseline endorsement of motor abnormalities predicted future depression symptoms at one-year follow-up.

Conclusions
These findings suggest that motor signs reflect a novel, promising future direction for examining vulnerability to depression risk in early adolescence.

Functional connectome mediates the association between sleep disturbance and mental health in preadolescence: A longitudinal mediation study

Yang FN, Liu TT, Wang Z. Functional connectome mediates the association between sleep disturbance and mental health in preadolescence: A longitudinal mediation study. Hum Brain Mapp. 2022 Jan 18. doi: 10.1002/hbm.25772. Epub ahead of print. PMID: 35040524.

Sleep disturbance is known to be associated with various mental disorders and often precedes the onset of mental disorders in youth. Given the increasingly acknowledged bidirectional influence between sleep disturbance and mental disorders, we aim to identify a shared neural mechanism that underlies sleep disturbance and mental disorders in preadolescents. We analyzed a dataset of 9,350 9-10 year-old children, among whom 8,845 had 1-year follow-up data, from the Adolescent Brain Cognitive Development (ABCD) study. Linear mixed-effects models, mediation analysis, and longitudinal mediation analysis were used to investigate the relationship between sleep disturbance, mental disorders, and resting-state network connectivity. Out of 186 unique connectivities, the effect of total sleep disturbance (TSP, from Sleep Disturbance Scale) and mental problems (MP, from Child Behavior Checklist) converged in the default mode network (DMN) and the dorsal attention network (DAN). Within- and between-network connectivities (DMN-DAN, DMN-DMN, DAN-DAN) mediated the relationship between baseline TSD and MP at 1-year follow-up and the relationship between baseline MP and TSD at 1-year follow-up. The pathway model in which sleep disturbance and mental problems affect each other through two anticorrelated brain networks (DMN and DAN) suggests a common neural mechanism between them. Longitudinally, a less segregated DMN and DAN is associated with negative outcomes on mental well-being and sleep disturbance a year later. These findings have important implications for the design of prevention and neurofeedback intervention for mental disorders and sleep problems.

Associations between cognition and polygenic liability to substance involvement in middle childhood: Results from the ABCD study

Paul SE, Hatoum AS, Barch DM, Thompson WK, Agrawal A, Bogdan R, Johnson EC (2022). Associations between cognition and polygenic liability to substance involvement in middle childhood: Results from the ABCD study. Drug and Alcohol Dependence, Volume 232, 1 March 2022, 109277, https://doi.org/10.1016/j.drugalcdep.2022.109277.

Background
Cognition is robustly associated with substance involvement. This relationship is attributable to multiple factors, including genetics, though such contributions show inconsistent patterns in the literature. For instance, genome-wide association studies point to potential positive relationships between educational achievement and common substance use but negative relationships with heavy and/or problematic substance use.

Methods
We estimated associations between polygenic risk for substance involvement (i.e., alcohol, tobacco, and cannabis use and problematic use) and cognition subfacets (i.e., general ability, executive function, learning/memory) derived from confirmatory factor analysis among 3205 substance naïve children (ages 9–10) of European ancestry who completed the baseline session of the Adolescent Brain Cognitive Development (ABCD) Study.

Findings
Polygenic risk for lifetime cannabis use was positively associated with all three facets of cognitive ability (Bs ≥ 0.045, qs ≤ 0.044). No other substance polygenic risk scores showed significant associations with cognition after adjustment for multiple testing (|Bs|≤0.033, qs ≥ 0.118).

Conclusions
Polygenic liability to lifetime cannabis use, but not use disorder, was positively associated with cognitive performance among substance-naïve children, possibly reflecting shared genetic overlap with openness to experience or the influence of genetic variance associated with socioeconomic status. Our lack of findings for the other polygenic scores may reflect ascertainment differences between the genome-wide association study (GWAS) samples and the current sample and/or the young age of the present sample. As longitudinal data in ABCD are collected, this sample may be useful for disentangling putatively causal or predispositional influences of substance use and misuse on cognition.

The ABCD Study: Brain Heterogeneity in Intelligence During a Neurodevelopmental Transition Stage

Zhao Q, Voon V, Zhang L, Shen C, Zhang J, Feng J. The ABCD Study: Brain Heterogeneity in Intelligence During a Neurodevelopmental Transition Stage. Cereb Cortex. 2022 Jan 15:bhab403. doi: 10.1093/cercor/bhab403. Epub ahead of print. PMID: 35037940.

A complex curvilinear relationship exists between intelligence and age during the neurodevelopment of cortical thickness. To parse out a more fine-grained relationship between intelligence and cortical thickness and surface area, we used a large-scale data set focusing on a critical transition juncture in neurodevelopment in preadolescence. Cortical thickness was derived from T1-weighted structural magnetic resonance images of a large sample of 9- and 11-year-old children from the Adolescent Brain Cognitive Development study. The NIH Toolbox Cognition Battery composite scores, which included fluid, crystallized, and total scores, were used to assess intelligence. Using a double generalized linear model, we assessed the independent association between the mean and dispersion of cortical thickness/surface area and intelligence. Higher intelligence in preadolescents was associated with higher mean cortical thickness in orbitofrontal and primary sensory cortices but with lower thickness in the dorsolateral and medial prefrontal cortex and particularly in the rostral anterior cingulate. The rostral anterior cingulate findings were particularly evident across all subscales of intelligence. Higher intelligence was also associated with greater interindividual similarity in the rostral cingulate. Intelligence during this key transition juncture in preadolescence appears to reflect a dissociation between the cortical development of basic cognitive processes and higher-order executive and motivational processes.

General Psychopathology, Cognition, and the Cerebral Cortex in 10-Year-Old Children: Insights From the Adolescent Brain Cognitive Development Study

Patel Y, Parker N, Salum GA, Pausova Z, Paus T. General Psychopathology, Cognition, and the Cerebral Cortex in 10-Year-Old Children: Insights From the Adolescent Brain Cognitive Development Study. Front Hum Neurosci. 2022 Jan 13;15:781554. doi: 10.3389/fnhum.2021.781554. PMID: 35145385; PMCID: PMC8823367.

General psychopathology and cognition are likely to have a bidirectional influence on each other. Yet, the relationship between brain structure, psychopathology, and cognition remains unclear. This brief report investigates the association between structural properties of the cerebral cortex [surface area, cortical thickness, intracortical myelination indexed by the T1w/T2w ratio, and neurite density assessed by restriction spectrum imaging (RSI)] with general psychopathology and cognition in a sample of children from the Adolescent Brain Cognitive Development (ABCD) study. Higher levels of psychopathology and lower levels of cognitive ability were associated with a smaller cortical surface area. Inter-regionally-across the cerebral cortex-the strength of association between an area and psychopathology is strongly correlated with the strength of association between an area and cognition. Taken together, structural deviations particularly observed in the cortical surface area influence both psychopathology and cognition.

Corrigendum to “Microstructural development from 9 to 14 years: Evidence from the ABCD Study”

Palmer CE, Pecheva D, Iversen JR, Hagler DJ Jr, Sugrue L, Nedelec P, Fan CC, Thompson WK, Jernigan TL, Dale AM. Corrigendum to “Microstructural development from 9 to 14 years: Evidence from the ABCD Study” [Dev. Cognit. Neurosci. 53 (2022) 101044]. Dev Cogn Neurosci. 2022 Jan 13:101063. doi: 10.1016/j.dcn.2022.101063. Epub ahead of print. Erratum for: Dev Cogn Neurosci. 2021 Dec 3;53:101044. PMID: 35034850.

Parental psychological problems were associated with higher screen time and the use of mature-rated media in children

Pulkki-Raback L, Barnes JD, Elovainio M, Hakulinen C, Sourander A, Tremblay MS, Guerrero MD. Parental psychological problems were associated with higher screen time and the use of mature-rated media in children. Acta Paediatr. 2022 Jan 12. doi: 10.1111/apa.16253. Epub ahead of print. PMID: 35023210.

Aim: Parents’ psychological problems may affect children’s screen time, but research has been scarce. We examined the association between parental psychological problems and children’s screen media behaviours in a nationally representative sample.

Methods: The participants were from the Adolescent Brain Cognitive Development study, recruited by probability sampling from the USA population. Children reported their use of TV, videos, video games, social media, and mature-rated media. The parents (85% mothers) reported psychological problems using the Adult Self-Report questionnaire.

Results: In 10,650 children (5,112 girls, 5,538 boys) aged 9.9±0.6 years, presence of parental psychological problems was associated with children spending more daily time on screen media and with meeting the recommendation of ≤2 daily hours less often than children whose parents did not have psychological problems. Parental psychological problems were associated with children’s TV watching, video watching and gaming but not with using social media. Parental internalising problems were associated with children watching mature-rated movies (odds ratio [OR] =1.14, 95% confidence interval [CI]=1.00, 1.30) and playing mature-rated games (OR=1.27, 95% CI=1.11, 1.45).

Conclusion: Presence of parental psychological problems is associated with higher screen time and use of mature-rated media in children. This cross-sectional study was not able to examine causal associations.

Moderate-to-vigorous intensity physical activity among adolescents in the USA during the COVID-19 pandemic

Nagata JM, Cortez CA, Dooley EE, Iyer P, Ganson KT, Gabriel KP (2022). Moderate-to-vigorous intensity physical activity among adolescents in the USA during the COVID-19 pandemic. Preventive Medicine Reports, Volume 25, February 2022, 101685. https://doi.org/10.1016/j.pmedr.2021.101685

This study aimed to evaluate adolescents’ moderate-to-vigorous intensity physical activity (MVPA) during the COVID-19 pandemic with regards to sociodemographic characteristics and determine mental health and resiliency factors associated with MVPA among a diverse national sample of adolescents ages 10–14 years. Data were collected during the pandemic in May 2020 from the Adolescent Brain Cognitive Development Study (ABCD, N = 5,153), a national prospective cohort study in the U.S. MVPA was quantified as the product of reported duration and frequency (hours per week), which was further summarized as the proportion meeting age-appropriate 2018 Physical Activity Guidelines for Americans. A similar estimate was generated using MVPA data collected prior to the pandemic. Mental health and resiliency measures were collected during the pandemic. Regression models examined associations between mental health or resiliency measures and MVPA during the pandemic. Median MVPA was 2 h per week (IQR 0, 6). Overall, the percentage of the cohort meeting MVPA guidelines decreased from 16.1% (pre-pandemic) to 8.9% (during the pandemic). Racial/ethnic minority adolescents and adolescents from lower socioeconomic backgrounds were significantly less likely to meet MVPA guidelines during the pandemic. Poorer mental health, COVID-related worry, and stress were associated with lower MVPA, while more social support and coping behaviors were associated with higher MVPA during the pandemic. In this large, national sample of adolescents, the proportion of those meeting MVPA Guidelines was lower during the COVID-19 pandemic, with significant disparities by race/ethnicity and socioeconomic status. Interventions to promote social support and coping behaviors may improve MVPA levels among adolescents during the pandemic.

Measurement of Gender and Sexuality in the Adolescent Brain Cognitive Development (ABCD) Study

Alexandra S. Potter, Sarahjane L. Dube, Lisa C. Barrios, Susan Bookheimer, Abigail Espinoza, Sarah W. Feldstein Ewing, Edward G. Freedman, Elizabeth A. Hoffman, Masha Ivanova, Hailee Jefferys, Erin C. McGlade, Susan F. Tapert, Michelle M Johns (2022). Measurement of Gender and Sexuality in the Adolescent Brain Cognitive Development (ABCD) Study, Developmental Cognitive Neuroscience, Volume 53, February 2022, 101057, ISSN 1878-9293, https://doi.org/10.1016/j.dcn.2022.101057.

The Adolescent Brain Cognitive DevelopmentSM (ABCD) study is a longitudinal study of adolescent brain development and health that includes over 11,800 youth in the United States. The ABCD study includes broad developmental domains, and gender and sexuality are two of these with noted changes across late childhood and early adolescence. The Gender Identity and Sexual Health (GISH) workgroup recommends measures of gender and sexuality for the ABCD study, prioritizing those that are developmentally sensitive, capture individual differences in the experience of gender and sexuality, and minimize participant burden. This manuscript describes the gender and sexuality measures used in ABCD and provides guidance for researchers using these data. Data showing the utility of these measures and longitudinal trends are presented. Including assessment of gender and sexuality in ABCD allows for characterization of developmental trajectories of gender and sexuality, and the broad scope of ABCD data collection allows examination of identity development in an intersectional manner.

Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample

Wang B, Giannakopoulou O, Austin-Zimmerman I, Irizar H, Harju-Seppänen J, Zartaloudi E, Bhat A, McQuillin A, Kuchenbäcker K, Bramon E. Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample. Genes (Basel). 2022 Jan 3;13(1):106. doi: 10.3390/genes13010106. PMID: 35052446.

Verbal memory impairment is one of the most prominent cognitive deficits in psychosis. However, few studies have investigated the genetic basis of verbal memory in a neurodevelopmental context, and most genome-wide association studies (GWASs) have been conducted in European-ancestry populations. We conducted a GWAS on verbal memory in a maximum of 11,017 participants aged 8.9 to 11.1 years in the Adolescent Brain Cognitive Development Study®, recruited from a diverse population in the United States. Verbal memory was assessed by the Rey Auditory Verbal Learning Test, which included three measures of verbal memory: immediate recall, short-delay recall, and long-delay recall. We adopted a mixed-model approach to perform a joint GWAS of all participants, adjusting for ancestral background and familial relatedness. The inclusion of participants from all ancestries increased the power of the GWAS. Two novel genome-wide significant associations were found for short-delay and long-delay recall verbal memory. In particular, one locus (rs9896243) associated with long-delay recall was mapped to the NSF (N-Ethylmaleimide Sensitive Factor, Vesicle Fusing ATPase) gene, indicating the role of membrane fusion in adolescent verbal memory. Based on the GWAS in the European subset, we estimated the SNP-heritability to be 15% to 29% for the three verbal memory traits. We found that verbal memory was genetically correlated with schizophrenia, providing further evidence supporting verbal memory as an endophenotype for psychosis.

Association of maternal diabetes with offspring childhood hypothalamic gliosis

Olerich, K., Sewaybricker, L., Chandrasekaran, S., Melhorn, S., Kee, S., & Schur, E. A. (2022). Association of maternal diabetes with offspring childhood hypothalamic gliosis. American Journal of Obstetrics & Gynecology, 226(1), S157-S158.

Objective
Maternal diabetes (MDM) during pregnancy affects the future metabolic health of the offspring. One possible mechanism by which MDM could enduringly impact offspring health is via an effect on the fetal brain. Specifically, we hypothesize that in utero exposure to MDM contributes to long-term alterations in offspring brain microstructure, through an inflammatory process called gliosis, within the energy regulatory centers of the mediobasal hypothalamus (MBH). MBH gliosis, quantifiable by MRI, is associated with increased adiposity and insulin resistance in children and adults.

Study Design
This is an ancillary analysis of the Adolescent Brain Cognitive Development study of child brain development and health. Children (9-11y) with brain MRIs and a completed maternal pregnancy survey were included. The presence of MDM, during the child’s gestation, was our exposure. Using MRI analytic software, regions of interest were placed in the MBH and reference brain regions. Evidence of MBH gliosis was based on higher T2-signal ratios in the MBH compared to amygdala (MBH/AMY; outcome). Putamen (PUT)/AMY and MBH/PUT were negative and positive control ratios, respectively. Statistical testing was by linear mixed model, adjusted for child age, sex, ethnicity, BMI and study site.

Results
Our analysis included 273 children: 224 MDM-unexposed and 49 MDM-exposed. MDM-exposed children had higher birth weights, BMI z-scores and waist-height ratios (Table 1). Mean MBH/AMY T2-signal ratios were significantly higher in the MDM-exposed children, compared to unexposed, consistent with MBH gliosis (Fig. 1). A region-ratio*MDM-group interaction was significant (chi2(2): 6.13, p=0.046). Post hoc testing confirmed that mean MBH/AMY T2-signal ratios were significantly higher in the MDM-exposed children, compared to unexposed, as were positive, but not negative, control ratios (Fig 1).

Conclusion
MDM-exposed children display greater evidence of MBH gliosis. The association between MDM and offspring MBH gliosis represents one pathway by which the in utero environment may influence the long-term metabolic health of the offspring.

2021
The Emotional Word-Emotional Face Stroop task in the ABCD study: Psychometric validation and associations with measures of cognition and psychopathology

Smolker HR, Wang K, Luciana M, Bjork JM, Gonzalez R, Barch DM, McGlade EC, Kaiser RH, Friedman NP, Hewitt JK, Banich MT. The Emotional Word-Emotional Face Stroop task in the ABCD study: Psychometric validation and associations with measures of cognition and psychopathology. Dev Cogn Neurosci. 2021 Dec 21;53:101054. doi: 10.1016/j.dcn.2021.101054. Epub ahead of print. PMID: 34954668.

Characterizing the interactions among attention, cognitive control, and emotion during adolescence may provide important insights into why this critical developmental period coincides with a dramatic increase in risk for psychopathology. However, it has proven challenging to develop a single neurobehavioral task that simultaneously engages and differentially measures these diverse domains. In the current study, we describe properties of performance on the Emotional Word-Emotional Face Stroop (EWEFS) task in the Adolescent Brain Cognitive Development (ABCD) Study, a task that allows researchers to concurrently measure processing speed/attentional vigilance (i.e., performance on congruent trials), inhibitory control (i.e., Stroop interference effect), and emotional information processing (i.e., difference in performance on trials with happy as compared to angry distracting faces). We first demonstrate that the task manipulations worked as designed and that Stroop performance is associated with multiple cognitive constructs derived from different measures at a prior time point. We then show that Stroop metrics tapping these three domains are preferentially associated with aspects of externalizing psychopathology and inattention. These results highlight the potential of the EWEFS task to help elucidate the longitudinal dynamics of attention, inhibitory control, and emotion across adolescent development, dynamics which may be altered by level of psychopathology.

Impact of COVID-19 on Youth With ADHD: Predictors and Moderators of Response to Pandemic Restrictions on Daily Life

Rosenthal E, Franklin-Gillette S, Jung HJ, Nelson A, Evans SW, Power TJ, Yerys BE, Dever BV, Reckner E, DuPaul GJ. Impact of COVID-19 on Youth With ADHD: Predictors and Moderators of Response to Pandemic Restrictions on Daily Life. J Atten Disord. 2021 Dec 17:10870547211063641. doi: 10.1177/10870547211063641. Epub ahead of print. PMID: 34920689.

We examined COVID-19 symptoms and infection rates, disruptions to functioning, and moderators of pandemic response for 620 youth with ADHD and 614 individually matched controls (70% male; Mage = 12.4) participating in the Adolescent Brain and Cognitive Development study. There were no group differences in COVID-19 infection rate; however, youth with ADHD were more likely to exhibit COVID-19 symptoms (d = 0.25), greater sleep problems (d = -0.52), fear and negative emotions to infection risk (d = -0.56), trouble with remote learning (d = -0.54), rule-breaking behavior related to COVID-19 restrictions (d = -0.23), family conflict (d = -0.13), and were less prepared for the next school year (d = 0.38). Youth with ADHD were less responsive to protective environmental variables (e.g., parental monitoring, school engagement) during the pandemic and may need more specialized support with return to in-person schooling and daily activities.

One-year predictions of delayed reward discounting in the adolescent brain cognitive development study

Owens, M. M., Hahn, S., Allgaier, N., MacKillop, J., Albaugh, M., Yuan, D., Juliano, A., Potter, A., & Garavan, H. (2021). One-year predictions of delayed reward discounting in the adolescent brain cognitive development study. Experimental and Clinical Psychopharmacology. Advance online publication. https://doi.org/10.1037/pha0000532

Delayed reward discounting (DRD) refers to the extent to which an individual devalues a reward based on a temporal delay and is known to be elevated in individuals with substance use disorders and many mental illnesses. DRD has been linked previously with both features of brain structure and function, as well as various behavioral, psychological, and life-history factors. However, there has been little work on the neurobiological and behavioral antecedents of DRD in childhood. This is an important question, as understanding the antecedents of DRD can provide signs of mechanisms in the development of psychopathology. The present study used baseline data from the Adolescent Brain Cognitive Development Study (N = 4,042) to build machine learning models to predict DRD at the first follow-up visit, 1 year later. In separate machine learning models, we tested elastic net regression, random forest regression, light gradient boosting regression, and support vector regression. In five-fold cross-validation on the training set, models using an array of questionnaire/task variables were able to predict DRD, with these findings generalizing to a held-out (i.e., “lockbox”) test set of 20% of the sample. Key predictive variables were neuropsychological test performance at baseline, socioeconomic status, screen media activity, psychopathology, parenting, and personality. However, models using magnetic resonance imaging (MRI)-derived brain variables did not reliably predict DRD in either the cross-validation or held-out test set. These results suggest a combination of questionnaire/task variables as antecedents of excessive DRD in late childhood, which may presage the development of problematic substance use in adolescence.

Parent-adolescent discrepancies in adolescent recreational screen time reporting during the COVID-19 pandemic

Nagata JM, Cortez CA, Iyer P, Ganson KT, Chu J, Conroy AA. Parent-adolescent discrepancies in adolescent recreational screen time reporting during the COVID-19 pandemic. Acad Pediatr. 2021 Dec 16:S1876-2859(21)00623-9. doi: 10.1016/j.acap.2021.12.008. Epub ahead of print. PMID: 34923146.

Objective: To describe the relationship between parent and adolescent reports of adolescent recreational screen time and to determine sociodemographic predictors of recreational screen time reporting differences during the COVID-19 pandemic.

Methods: We analyzed data from the Adolescent Brain Cognitive Development Study (ABCD, N=5,335, ages 10-14) a national prospective cohort study in the US collected in May 2020. We compared parent-reported, adolescent-reported, and a parent-adolescent differences in recreational screen time hours per day across five screen categories.

Results: Adolescents’ total recreational screen time per day was reported as 4.46 hours by parents and 3.87 hours by adolescents. Parents reported higher levels of their child’s texting, video chatting, and total recreational screen time, while adolescents reported higher multi-player gaming and social media use. Larger discrepancies in total recreational screen time were found in older, Black, and Latino/Hispanic adolescents. Larger discrepancies in total recreational screen time were also found among unmarried/unpartnered parents.

Conclusions: Given discrepancies in parent-adolescent recreational screen time reporting during the pandemic, a period of high screen use, pediatricians should encourage family discussions about adolescent media use through the development of a Family Media Use Plan. The digital media industry could provide more opportunities for parental monitoring of recreational screen time within product designs.

Longitudinal Impact of Childhood Adversity on Early Adolescent Mental Health During the COVID-19 Pandemic in the ABCD Study® Cohort: Does Race or Ethnicity Moderate Findings?

Stinson EA, Sullivan RM, Peteet BJ, Tapert SF, Baker FC, Breslin FJ, Dick AS, Gonzalez MR, Guillaume M, Marshall AT, McCabe CJ, Pelham WE 3rd, Van Rinsveld AM, Sheth CS, Sowell ER, Wade NE, Wallace AL, Lisdahl KM (2021). Longitudinal Impact of Childhood Adversity on Early Adolescent Mental Health During the COVID-19 Pandemic in the ABCD Study® Cohort: Does Race or Ethnicity Moderate Findings?, Biological Psychiatry Global Open Science, Volume 1, Issue 4, December 2021, Pages 324-335, ISSN 2667-1743. https://doi.org/10.1016/j.bpsgos.2021.08.007.

Background
During the COVID-19 pandemic in the United States, mental health among youth has been negatively affected. Youth with a history of adverse childhood experiences (ACEs), as well as youth from minoritized racial-ethnic backgrounds, may be especially vulnerable to experiencing COVID-19–related distress. The aims of this study are to examine whether exposure to pre-pandemic ACEs predicts mental health during the COVID-19 pandemic in youth and whether racial-ethnic background moderates these effects.

Methods
From May to August 2020, 7983 youths (mean age, 12.5 years; range, 10.6–14.6 years) in the Adolescent Brain Cognitive Development (ABCD) Study completed at least one of three online surveys measuring the impact of the pandemic on their mental health. Data were evaluated in relation to youths’ pre-pandemic mental health and ACEs.

Results
Pre-pandemic ACE history significantly predicted poorer mental health across all outcomes and greater COVID-19–related stress and impact of fears on well-being. Youths reported improved mental health during the pandemic (from May to August 2020). While reporting similar levels of mental health, youths from minoritized racial-ethnic backgrounds had elevated COVID-19–related worry, stress, and impact on well-being. Race and ethnicity generally did not moderate ACE effects. Older youths, girls, and those with greater pre-pandemic internalizing symptoms also reported greater mental health symptoms.

Conclusions
Youths who experienced greater childhood adversity reported greater negative affect and COVID-19–related distress during the pandemic. Although they reported generally better mood, Asian American, Black, and multiracial youths reported greater COVID-19–related distress and experienced COVID-19–related discrimination compared with non-Hispanic White youths, highlighting potential health disparities.

Prevalence, predictors, and treatment of eating disorders in children: A national study

Sanzari, C., Levin, R., & Liu, R. (2021). Prevalence, predictors, and treatment of eating disorders in children: A national study. Psychological Medicine, 1-8. doi:10.1017/S0033291721004992\

Background
Although the prevalence rates of preadolescent eating disorders (EDs) are on the rise, considerably less is known about the correlates and treatment of EDs in this age group. Clarifying the epidemiology of EDs in preadolescent children is a necessary first step to understand the nature and scope of this problem in this age group.

Methods
Analysis of data collected in the ABCD Study release 2.0.1. The ABCD cohort was a population-based sample that consisted of 11 721 children ages 9–10 years. Measures included reports of a lifetime and current mental disorders determined using a diagnostic interview for DSM-5 disorders, sociodemographic factors, and psychiatric treatment utilization.

Results
The lifetime prevalence of EDs was 0.95%. Being Black, multiracial, having unmarried parents, and family economic insecurity were significant predictors for developing an ED. Among psychiatric conditions, the major depressive disorder was most robustly associated with EDs in both cross-sectional and temporal analyses. Only 47.40% of children who had a lifetime ED received some type of psychiatric treatment. EDs were not a significant predictor of psychiatric treatment utilization after accounting for sex, sexual orientation, parent marital status, economic insecurity, and all other psychiatric diagnoses.

Conclusions
Despite increasing prevalence rates of preadolescent EDs, the current findings suggest that the majority of children with these disorders remain untreated. Devoting increased attention and resources to reaching families of children with EDs with the least means for receiving care, and screening for EDs in children with depression, may be important steps for reducing this unmet need.

Brain network coupling associated with cognitive performance varies as a function of a child’s environment in the ABCD study

Ellwood-Lowe, M.E., Whitfield-Gabrieli, S. & Bunge, S.A. Brain network coupling associated with cognitive performance varies as a function of a child’s environment in the ABCD study. Nat Commun 12, 7183 (2021). https://doi.org/10.1038/s41467-021-27336-y

Prior research indicates that lower resting-state functional coupling between two brain networks, lateral frontoparietal network (LFPN) and default mode network (DMN), relates to cognitive test performance, for children and adults. However, most of the research that led to this conclusion has been conducted with non-representative samples of individuals from higher-income backgrounds, and so further studies including participants from a broader range of socioeconomic backgrounds are required. Here, in a pre-registered study, we analyzed resting-state fMRI from 6839 children ages 9–10 years from the ABCD dataset. For children from households defined as being above poverty (family of 4 with income > $25,000, or family of 5+ with income > $35,000), we replicated prior findings; that is, we found that better performance on cognitive tests correlated with weaker LFPN-DMN coupling. For children from households defined as being in poverty, the direction of association was reversed, on average: better performance was instead directionally related to stronger LFPN-DMN connectivity, though there was considerable variability. Among children in households below poverty, the direction of this association was predicted in part by features of their environments, such as school type and parent-reported neighborhood safety. These results highlight the importance of including representative samples in studies of child cognitive development.

Microstructural development from 9 to 14 years: Evidence from the ABCD Study

Clare E. Palmer, Diliana Pecheva, John R. Iversen, Donald J. Hagler, Leo Sugrue, Pierre Nedelec, Chun Chieh Fan, Wesley K. Thompson, Terry L. Jernigan, Anders M. Dale, Microstructural development from 9 to 14 years: Evidence from the ABCD Study, Developmental Cognitive Neuroscience, Volume 53, 2022, 101044, ISSN 1878-9293,https://doi.org/10.1016/j.dcn.2021.101044.

During late childhood behavioral changes, such as increased risk-taking and emotional reactivity, have been associated with the maturation of cortico-cortico and cortico-subcortical circuits. Understanding microstructural changes in both white matter and subcortical regions may aid our understanding of how individual differences in these behaviors emerge. Restriction spectrum imaging (RSI) is a framework for modelling diffusion-weighted imaging that decomposes the diffusion signal from a voxel into hindered, restricted, and free compartments. This yields greater specificity than conventional methods of characterizing diffusion. Using RSI, we quantified voxelwise restricted diffusion across the brain and measured age associations in a large sample (n = 8086) from the Adolescent Brain and Cognitive Development (ABCD) study aged 9–14 years. Older participants showed a higher restricted signal fraction across the brain, with the largest associations in subcortical regions, particularly the basal ganglia and ventral diencephalon. Importantly, age associations varied with respect to the cytoarchitecture within white matter fiber tracts and subcortical structures, for example age associations differed across thalamic nuclei. This suggests that age-related changes may map onto specific cell populations or circuits and highlights the utility of voxelwise compared to ROI-wise analyses. Future analyses will aim to understand the relevance of this microstructural developmental for behavioral outcomes.

Adolescent Brain Cognitive Development (ABCD) study Linked External Data (LED): Protocol and practices for geocoding and assignment of environmental data

Fan CC, Marshall A, Smolker H, Gonzalez MR, Tapert SF, Barch DM, Sowell E, Dowling GJ, Cardenas-Iniguez C, Ross J, Thompson WK, Herting MM. Adolescent Brain Cognitive Development (ABCD) study Linked External Data (LED): Protocol and practices for geocoding and assignment of environmental data. Dev Cogn Neurosci, Volume 52, December 2021, 101030. doi: 10.1016/j.dcn.2021.101030. Epub ahead of print. PMID: 34891080.

Our brain is constantly shaped by our immediate environments, and while some effects are transient, some have long-term consequences. Therefore, it is critical to identify which environmental risks have evident and long-term impact on brain development. To expand our understanding of the environmental context of each child, the Adolescent Brain Cognitive Development (ABCD) Study® incorporates the use of geospatial location data to capture a range of individual, neighborhood, and state level data based on the child’s residential location in order to elucidate the physical environmental contexts in which today’s youth are growing up. We review the major considerations and types of geocoded information incorporated by the Linked External Data Environmental (LED) workgroup to expand on the built and natural environmental constructs in the existing and future ABCD Study data releases. Understanding the environmental context of each youth furthers the consortium’s mission to understand factors that may influence individual differences in brain development, providing the opportunity to inform public policy and health organization guidelines for child and adolescent health.

Measurement matters: An individual differences examination of family socioeconomic factors, latent dimensions of children’s experiences, and resting state functional brain connectivity in the ABCD sample

DeJoseph ML, Herzberg MP, Sifre RD, Berry D, Thomas KM. Measurement matters: An individual differences examination of family socioeconomic factors, latent dimensions of children’s experiences, and resting state functional brain connectivity in the ABCD sample. Dev Cogn Neurosci. 2021 Dec 8;53:101043. doi: 10.1016/j.dcn.2021.101043. Epub ahead of print. PMID: 34915436.

The variation in experiences between high and low-socioeconomic status contexts are posited to play a crucial role in shaping the developing brain and may explain differences in child outcomes. Yet, examinations of SES and brain development have largely been limited to distal proxies of these experiences (e.g., income comparisons). The current study sought to disentangle the effects of multiple socioeconomic indices and dimensions of more proximal experiences on resting-state functional connectivity (rsFC) in a sample of 7834 youth (aged 9-10 years) from the Adolescent Brain Cognitive Development (ABCD) study. We applied moderated nonlinear factor analysis (MNLFA) to establish measurement invariance among three latent environmental dimensions of experience (material/economic deprivation, caregiver social support, and psychosocial threat). Results revealed measurement biases as a function of child age, sex, racial group, family income, and parental education, which were statistically adjusted in the final MNLFA scores. Mixed-effects models demonstrated that socioeconomic indices and psychosocial threat differentially predicted variation in frontolimbic networks, and threat statistically moderated the association between income and connectivity between the dorsal and ventral attention networks. Findings illuminate the importance of reducing measurement biases to gain a more socioculturally-valid understanding of the complex and nuanced links between socioeconomic context, children’s experiences, and neurodevelopment.

Reward Processing in Children With Psychotic-Like Experiences

Harju-Seppänen J, Irizar H, Bramon E, Blakemore SJ, Mason L, Bell V. Reward Processing in Children With Psychotic-Like Experiences. Schizophr Bull Open. 2021 Dec 4;3(1):sgab054. doi: 10.1093/schizbullopen/sgab054. PMID: 35036918; PMCID: PMC8756103.

Alterations to striatal reward pathways have been identified in individuals with psychosis. They are hypothesized to be a key mechanism that generate psychotic symptoms through the production of aberrant attribution of motivational salience and are proposed to result from accumulated childhood adversity and genetic risk, making the striatal system hyper-responsive to stress. However, few studies have examined whether children with psychotic-like experiences (PLEs) also exhibit these alterations, limiting our understanding of how differences in reward processing relate to hallucinations and delusional ideation in childhood. Consequently, we examined whether PLEs and PLE-related distress were associated with reward-related activation in the nucleus accumbens (NAcc). The sample consisted of children (N = 6718) from the Adolescent Brain Cognitive Development (ABCD) study aged 9-10 years who had participated in the Monetary Incentive Delay (MID) task in functional MRI. We used robust mixed-effects linear regression models to investigate the relationship between PLEs and NAcc activation during the reward anticipation and reward outcome stages of the MID task. Analyses were adjusted for gender, household income, ethnicity, depressive symptoms, movement in the scanner, pubertal development, scanner ID, subject and family ID. There was no reliable association between PLEs and alterations to anticipation- or outcome-related striatal reward processing. We discuss the implications for developmental models of psychosis and suggest a developmental delay model of how PLEs may arise at this stage of development.

Associations Between Traumatic Stress, Brain Volumes and Post-traumatic Stress Disorder Symptoms in Children: Data from the ABCD Study

Bustamante D, Amstadter AB, Pritikin JN, Brick TR, Neale MC. Associations Between Traumatic Stress, Brain Volumes and Post-traumatic Stress Disorder Symptoms in Children: Data from the ABCD Study. Behav Genet. 2021 Dec 3. doi: 10.1007/s10519-021-10092-6. Epub ahead of print. PMID: 34860306.

Reduced volumes in brain regions of interest (ROIs), primarily from adult samples, are associated with posttraumatic stress disorder (PTSD). We extended this work to children using data from the Adolescent Brain Cognitive Development (ABCD) Study® (N = 11,848; Mage = 9.92). Structural equation modeling and an elastic-net (EN) machine-learning approach were used to identify potential effects of traumatic events (TEs) on PTSD symptoms (PTSDsx) directly, and indirectly via the volumes 300 subcortical and cortical ROIs. We then estimated the genetic and environmental variation in the phenotypes. TEs were directly associated with PTSDsx (r = 0.92) in children, but their indirect effects (r < 0.0004)-via the volumes of EN-identified subcortical and cortical ROIs-were negligible at this age. Additive genetic factors explained a modest proportion of the variance in TEs (23.4%) and PTSDsx (21.3%), and accounted for most of the variance of EN-identified volumes of four of the five subcortical (52.4-61.8%) three of the nine cortical ROIs (46.4-53.3%) and cerebral white matter in the left hemisphere (57.4%). Environmental factors explained most of the variance in TEs (C = 61.6%, E = 15.1%), PTSDsx (residual-C = 18.4%, residual-E = 21.8%), right lateral ventricle (C = 15.2%, E = 43.1%) and six of the nine EN-identified cortical ROIs (C = 4.0-13.6%, E = 56.7-74.8%). There is negligible evidence that the volumes of brain ROIs are associated with the indirect effects of TEs on PTSDsx at this age. Overall, environmental factors accounted for more of the variation in TEs and PTSDsx. Whereas additive genetic factors accounted for most of the variability in the volumes of a minority of cortical and in most of subcortical ROIs.

Psychotic-like experiences associated with sleep disturbance and brain volumes in youth: Findings from the adolescent brain cognitive development study

Lunsford-Avery JR, Damme KSF, Vargas T, Sweitzer MM, Mittal VA. Psychotic-like experiences associated with sleep disturbance and brain volumes in youth: Findings from the adolescent brain cognitive development study. Association for Child and Adolescent Mental Health. Dec. 2, 2021. https://doi.org/10.1002/jcv2.12055.

Background
Sleep disturbance is characteristic of schizophrenia and at-risk populations, suggesting a possible etiological role in psychosis. Biological mechanisms underlying associations between sleep and psychosis vulnerability are unclear, although reduced sleep-regulatory brain structure volumes are a proposed contributor. This study is the first to examine relationships between psychotic-like experiences (PLEs; subclinical symptoms reflecting psychosis vulnerability/risk), sleep, and brain volumes in youth.

Methods
Brain volumes of five sleep-related structures were examined in relation to PLEs and difficulties initiating and maintaining sleep (DIMS) in 9,260 9- to 11-year-olds participating in the Adolescent Brain Cognitive Development (ABCD) study. Analytic models examined relationships between DIMS, PLEs, and brain volumes, as well as DIMS as a mediator of brain volume–PLEs relationships. Although sleep regulation structures (i.e., thalamus, basal forebrain, and hypothalamus) were of primary interest, other potentially relevant structures to sleep-related functioning and psychosis (i.e., hippocampus and amygdala) were also examined.

Results
PLEs were associated with increased DIMS as well as reduced volume in some, but not all, brain structures, including the thalamus and basal forebrain in children. DIMS was also associated with reduced left thalamus volume in youth. Increased DIMS partially, statistically mediated the relationship between left thalamic volume and PLEs, although the effect was relatively small.

Conclusions
Results highlight left thalamic volume as a potential neural mechanism underlying sleep disturbances and PLEs in childhood. Future studies should assess causal relationships between sleep, PLEs, and brain structure across adolescent development, interactions with other psychosis risk factors, and the role of sleep interventions in prevention of psychosis and a range of psychiatric conditions across the lifespan.

Association of Outdoor Ambient Fine Particulate Matter With Intracellular White Matter Microstructural Properties Among Children

Burnor E, Cserbik D, Cotter DL, Palmer CE, Ahmadi H, Eckel SP, Berhane K, McConnell R, Chen JC, Schwartz J, Jackson R, Herting MM. Association of Outdoor Ambient Fine Particulate Matter With Intracellular White Matter Microstructural Properties Among Children. JAMA Netw Open. 2021 Dec 1;4(12):e2138300. doi: 10.1001/jamanetworkopen.2021.38300. PMID: 34882178.

Importance: Outdoor particulate matter 2.5 μm or less in diameter (PM2.5) is a ubiquitous environmental neurotoxicant that may affect the developing brain. Little is known about associations between PM2.5 and white matter connectivity.

Objectives: To assess associations between annual residential PM2.5 exposure and white matter microstructure health in a US sample of children 9 to 10 years of age and to examine whether associations are specific to certain white matter pathways or vary across neuroimaging diffusion markers reflective of intracellular and extracellular microstructural processes.

Design, setting, and participants: This cross-sectional study, the Adolescent Brain and Cognitive Development (ABCD) Study, was composed of 21 study sites across the US and used baseline data collected from children 9 to 10 years of age from September 1, 2016, to October 15, 2018. Data analysis was performed from September 15, 2020, to June 30, 2021.

Exposures: Annual mean PM2.5 exposure estimated by ensemble-based models and assigned to the primary residential addresses at baseline.

Main outcomes and measures: Diffusion-weighted imaging (DWI) and tractography were used to delineate white matter tracts. The biophysical modeling technique of restriction spectrum imaging (RSI) was implemented to examine total hindered diffusion and restricted isotropic and anisotropic intracellular diffusion in each tract. Hierarchical mixed-effects models with natural splines were used to analyze the associations between PM2.5 exposure and DWI.

Results: In a study population of 7602 children (mean [SD] age, 119.1 [7.42] months; 3955 [52.0%] female; 160 [ 21.%] Asian, 1025 [13.5%] Black, 1616 [21.3%] Hispanic, 4025 [52.9%] White, and 774 [10.2%] other [identified by parents as American Indian/Native American or Alaska Native; Native Hawaiian, Guamanian, Samoan, other Pacific Islander; Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, or other Asian; or other race]), associations were seen between annual ambient PM2.5 and hemispheric differences in white matter microstructure. Hemisphere-stratified models revealed significant associations between PM2.5 exposure and restricted isotropic intracellular diffusion in the left cingulum, in the left superior longitudinal fasciculus, and bilaterally in the fornix and uncinate fasciculus. In tracts with strong positive associations, a PM2.5 increase from 8 to 12 μg/m3 was associated with increases of 2.16% (95% CI, 0.49%-3.84%) in the left cingulum, 1.95% (95% CI, 0.43%-3.47%) in the left uncinate, and 1.68% (95% CI, 0.01%-3.34%) in the right uncinate. Widespread negative associations were observed between PM2.5 and mean diffusivity.

Conclusions and relevance: The findings of this cross-sectional study suggest that annual mean PM2.5 exposure during childhood is associated with increased restricted isotropic diffusion and decreased mean diffusivity of specific white matter tracts, potentially reflecting differences in the composition of white matter microarchitecture.

Internalizing-externalizing comorbidity and regional brain volumes in the ABCD study

Schettini E, Wilson S, Beauchaine TP. Internalizing-externalizing comorbidity and regional brain volumes in the ABCD study. Dev Psychopathol. 2021 Dec;33(5):1620-1633. doi: 10.1017/s0954579421000560. Epub 2021 Dec 7. PMID: 36238203; PMCID: PMC9555230.

Despite nonoverlapping diagnostic criteria, internalizing and externalizing disorders show substantial comorbidity. This comorbidity is attributable, at least in part, to transdiagnostic neuroaffective mechanisms. Both unipolar depression and externalizing disorders are characterized by structural and functional compromises in the striatum and its projections to the anterior cingulate cortex (ACC) and other frontal regions. Smaller volumes and dampened reward responding in these regions are associated with anhedonia and irritability – mood states that cut across the internalizing and externalizing spectra. In contrast, smaller amygdala volumes and dampened amygdala function differentiate externalizing disorders from internalizing disorders. Little is known, however, about associations between internalizing-externalizing comorbidity and brain volumes in these regions, or whether such patterns differ by sex. Using a transdiagnostic, research domain criteria (RDoC)-informed approach, we evaluate associations between heterotypic (Internalizing × Externalizing) symptom interactions and striatal, amygdalar, and ACC volumes among participants in the Adolescent Brain Cognitive Development study (N = 6,971, mean age 9.9 years, 51.6% female). Heterotypic symptoms were associated with ACC volumes for both sexes, over and above the main effects of internalizing and externalizing alone. However, heterotypic comorbidity was associated with larger ACC volumes for girls, but with smaller ACC volumes for boys. These findings suggest a need for further studies and transdiagnostic assessment by sex.

Racism-Related Diminished Returns of Socioeconomic Status on Adolescent Brain and Cognitive Development

Boyce S, Darvishi M, Marandi R, Rahmanian R, Akhtar S, Patterson J, Assari S. Racism-Related Diminished Returns of Socioeconomic Status on Adolescent Brain and Cognitive Development. Research in Health Science, 6(4):p1, December 2021, DOI:10.22158/rhs.v6n4p1

Socioeconomic status (SES) influences health, behaviors, and well-being. Emerging information suggests that SES effects on health may be in part be due to SES effects on brain development. We have conducted a mini review of U.S.-based studies examining SES effects on brain development to synthesize the existing knowledge on what brain structures and functions show large and consistent SES influences. We have reviewed SES effects on performance in various cognitive functions such as learning, memory, and language. Additionally, we have reviewed the emerging literature from the Adolescent Brain Cognitive Development (ABCD) study on the effects of social marginalization in reducing the effects of SES on children and youth brain development. These diminished returns of SES in minoritized youth are not due to genetics; rather, we argue that they stem from systemic and structural racism, social stratification, and marginalization that generate inequalities across the SES spectrum. As a result of these diminished returns, inequalities expand from low-SES to mid- and high SES sections of US society.

Predicting multilingual effects on executive function and individual connectomes in children: An ABCD study

Kwon YH, Yoo K, Nguyen H, Jeong Y, Chun MM. Predicting multilingual effects on executive function and individual connectomes in children: An ABCD study. Proc Natl Acad Sci U S A. 2021 Dec 7;118(49):e2110811118. doi: 10.1073/pnas.2110811118. PMID: 34845019.

While there is a substantial amount of work studying multilingualism’s effect on cognitive functions, little is known about how the multilingual experience modulates the brain as a whole. In this study, we analyzed data of over 1,000 children from the Adolescent Brain Cognitive Development (ABCD) Study to examine whether monolinguals and multilinguals differ in executive function, functional brain connectivity, and brain-behavior associations. We observed significantly better performance from multilingual children than monolinguals in working-memory tasks. In one finding, we were able to classify multilinguals from monolinguals using only their whole-brain functional connectome at rest and during an emotional n-back task. Compared to monolinguals, the multilingual group had different functional connectivity mainly in the occipital lobe and subcortical areas during the emotional n-back task and in the occipital lobe and prefrontal cortex at rest. In contrast, we did not find any differences in behavioral performance and functional connectivity when performing a stop-signal task. As a second finding, we investigated the degree to which behavior is reflected in the brain by implementing a connectome-based behavior prediction approach. The multilingual group showed a significant correlation between observed and connectome-predicted individual working-memory performance scores, while the monolingual group did not show any correlations. Overall, our observations suggest that multilingualism enhances executive function and reliably modulates the corresponding brain functional connectome, distinguishing multilinguals from monolinguals even at the developmental stage.

Big Data-Driven Brain Parcellation from fMRI: Impact of Cohort Heterogeneity on Functional Connectivity Maps

Brooks SJ, Parks SM, Stamoulis C. Big Data-Driven Brain Parcellation from fMRI: Impact of Cohort Heterogeneity on Functional Connectivity Maps. Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021:3133-3136. doi: 10.1109/EMBC46164.2021.9630267. PMID: 34891905.

Ongoing large-scale human brain studies are generating complex neuroimaging data from thousands of individuals that can be leveraged to derive data-driven, anatomically accurate brain parcellations. However, despite their promise and many strengths, these data are highly heterogeneous, a characteristic that may affect the anatomical accuracy and generalization of the template but has received relatively little attention. Using multiple similarity measures and thresholding approaches, this study investigated the topological intra- and inter-individual variability of restingstate (rs) functional edge maps (often used for brain parcellation), estimated from rs-fMRI connectivity in n = 5878 children from the Adolescent Brain Cognitive Development (ABCD) study. Findings from this initial investigation indicate that choosing a subject- vs cohort-based threshold for estimating edge maps from connectivity matrices does not significantly impact the map topology. In contrast, the choice of similarity measure and non-linear relationship between similarity and edge map sparsity may have a significant impact on map classification and the generation of parcellation atlases. Multi-level classification revealed multiple clusters with a potentially complex mapping onto biological variables beyond simple demographics.Clinical Relevance- Case-control neuroimaging studies should use domain-specific (e.g., demographics-specific) atlases for parcellating the brain, to improve accuracy and rigor of cohort comparisons. To be generalizable, such atlases need to be derived from large datasets, which are inherently heterogeneous. In a cohort of 5878 children (age ~9-10 years), this study systematically assessed the impact of heterogeneity and similarity of edge maps, which are derived from rs-fMRI connectivity and typically used to generate parcellation atlases.

Multimodal ensemble deep learning to predict disruptive behavior disorders in children

Menon, S. S., & Krishnamurthy, K. (2021). Multimodal ensemble deep learning to predict disruptive behavior disorders in children. Frontiers in Neuroinformatics, doi:http://dx.doi.org/10.3389/fninf.2021.742807

Oppositional defiant disorder and conduct disorder, collectively referred to as disruptive behavior disorders (DBDs), are prevalent psychiatric disorders in children. Early diagnosis of DBDs is crucial because they can increase the risks of other mental health and substance use disorders without appropriate psychosocial interventions and treatment. However, diagnosing DBDs is challenging as they are often comorbid with other disorders, such as attention-deficit/hyperactivity disorder, anxiety, and depression. In this study, a multimodal ensemble 3D convolutional neural network (CNN) deep learning model was used to classify children with DBDs and typically developing children. The study participants included 419 girls and 681 boys, aged 108 to 131 months who were enrolled in the Adolescent Brain Cognitive Development Study. Children were grouped based on the presence of DBDs (n=550) and typically developing (n=550); assessments were based on the scores from the Child Behavior Checklist and on the Schedule for Affective Disorders and Schizophrenia for School-age Children–Present and Lifetime version for DSM-5. The diffusion, structural, and resting-state functional magnetic resonance imaging (rs-fMRI) data were used as input data to the 3D CNN. The model achieved 72% accuracy in classifying children with DBDs with 70% sensitivity and 72% specificity. In addition, the discriminative power of the classifier was investigated by delineating the cortical and subcortical regions primarily involved in the prediction of DBDs using a gradient class activation map. The classification results were compared with those obtained using the three neuroimaging modalities individually, and a connectome-based graph CNN and a multi-scale recurrent neural network using only the rs-fMRI data.

Graph auto-encoding brain networks with applications to analyzing large-scale brain imaging datasets

Liu M, Zhang Z, Dunson DB. Graph auto-encoding brain networks with applications to analyzing large-scale brain imaging datasets. Neuroimage. 2021 Nov 22:118750. doi: 10.1016/j.neuroimage.2021.118750. Epub ahead of print. PMID: 34823023.

Brain structural associations with depression in a large early adolescent sample (the ABCD study®)

Shen X, MacSweeney N, Chan SWY, Barbu MC, Adams MJ, Lawrie SM, Romaniuk L, McIntosh AM, Whalley HC. Brain structural associations with depression in a large early adolescent sample (the ABCD study®), EClinicalMedicine, Volume 42, 2021, 101204, ISSN 2589-5370, https://doi.org/10.1016/j.eclinm.2021.101204.

Background
Depression is the leading cause of disability worldwide with > 50% of cases emerging before the age of 25 years. Large-scale neuroimaging studies in depression implicate robust structural brain differences in the disorder. However, most studies have been conducted in adults and therefore, the temporal origins of depression-related imaging features remain largely unknown. This has important implications for understanding aetiology and informing timings of potential intervention.

Methods
Here, we examine associations between brain structure (cortical metrics and white matter microstructural integrity) and depression ratings (from caregiver and child), in a large sample (N = 8634) of early adolescents (9 to 11 years old) from the US-based, Adolescent Brain and Cognitive Development (ABCD) Study®. Data was collected from 2016 to 2018.

Findings
We report significantly decreased global cortical and white matter metrics, and regionally in frontal, limbic and temporal areas in adolescent depression (Cohen’s d = -0⋅018 to -0⋅041, β = -0·019 to -0⋅057). Further, we report consistently stronger imaging associations for caregiver-reported compared to child-reported depression ratings. Divergences between reports (caregiver vs child) were found to significantly relate to negative socio-environmental factors (e.g., family conflict, absolute β = 0⋅048 to 0⋅169).

Interpretation
Depression ratings in early adolescence were associated with similar imaging findings to those seen in adult depression samples, suggesting neuroanatomical abnormalities may be present early in the disease course, arguing for the importance of early intervention. Associations between socio-environmental factors and reporter discrepancy warrant further consideration, both in the wider context of the assessment of adolescent psychopathology, and in relation to their role in aetiology.

Minding the Gap: Adolescent and Parent/Caregiver Reporter Discrepancies on Symptom Presence, Impact of Covariates, and Clinical Implications

Ford SH, McCoy TP. Minding the Gap: Adolescent and Parent/Caregiver Reporter Discrepancies on Symptom Presence, Impact of Covariates, and Clinical Implications. J Pediatr Health Care. 2021 Nov 18:S0891-5245(21)00238-8. doi: 10.1016/j.pedhc.2021.09.010. Epub ahead of print. PMID: 34802858.

Brain signatures in children who contemplate suicide: Learning from the large-scale ABCD study

Wiglesworth, A., Falke, C., Fiecas, M., Luciana, M., Cullen, K., & Klimes-Dougan, B. (2021). Brain signatures in children who contemplate suicide: Learning from the large-scale ABCD study. Psychological Medicine, 1-10. doi:10.1017/S0033291721004074

Background
Suicide is the second-leading cause of death in youth. Understanding the neural correlates of suicide ideation (SI) in children is crucial to ongoing efforts to understand and prevent youth suicide. This study characterized key neural networks during rest and emotion task conditions in an epidemiologically informed sample of children who report current, past, or no SI.

Methods
Data are from the adolescent brain cognitive development study, including 8248 children (ages 9–10; mean age = 119.2 months; 49.2% female) recruited from the community. Resting-state functional connectivity (RSFC) and activation to emotional stimuli in the salience (SN) and default mode (DMN) networks were measured through fMRI. Self-reported SI and clinical profiles were gathered. We examined the replicability of our model results through repeated sub-sample reliability analyses.

Results
Children with current SI (2.0%), compared to those without any past SI, showed lower DMN RSFC (B = −0.267, p < 0.001) and lower DMN activation in response to negative as compared to neutral faces (B = −0.204, p = 0.010). These results were robust to the effects of MDD, ADHD, and medication use. Sub-sample analysis further supported the robustness of these results. We did not find support for differences in SN RSFC or in SN activation to positive or negative stimuli for children with or without SI.

Conclusions
Results from a large brain imaging study using robust statistical approaches suggest aberrant DMN functioning in children with current suicide ideation. Findings suggest potential mechanisms that may be targeted in suicide prevention efforts.

Persistent and distressing psychotic-like experiences using adolescent brain cognitive development℠ study data

Karcher NR, Loewy RL, Savill M, Avenevoli S, Huber RS, Makowski C, Sher KJ, & Barch DM. Persistent and distressing psychotic-like experiences using adolescent brain cognitive development℠ study data. Mol Psychiatry (Nov. 16, 2021). https://doi.org/10.1038/s41380-021-01373-x

Childhood psychotic-like experiences (PLEs) are associated with a range of impairments; a subset of children experiencing PLEs will develop psychiatric disorders, including psychotic disorders. A potential distinguishing factor between benign PLEs versus PLEs that are clinically relevant is whether PLEs are distressing and/or persistent. The current study used three waves of Adolescent Brain Cognitive Development℠ (ABCD) study PLEs assessments to examine the extent to which persistent and/or distressing PLEs were associated with relevant baseline risk factors (e.g., cognition) and functioning/mental health service utilization domains. Four groups varying in PLE persistence and distress endorsement were created based on all available data in ABCD Release 3.0, with group membership not contingent on complete data: persistent distressing PLEs (n = 272), transient distressing PLEs (n = 298), persistent non-distressing PLEs (n = 221), and transient non-distressing PLEs (n = 536) groups. Using hierarchical linear models, results indicated youth with distressing PLEs, whether transient or persistent, showed delayed developmental milestones (β = 0.074, 95%CI:0.013,0.134) and altered structural MRI metrics (β = −0.0525, 95%CI:−0.100,−0.005). Importantly, distress interacted with PLEs persistence for the domains of functioning/mental health service utilization (β = 0.079, 95%CI:0.016,0.141), other reported psychopathology (β = 0.101, 95%CI:0.030,0.170), cognition (β = −0.052, 95%CI:0.−0.099,−0.002), and environmental adversity (β = 0.045, 95%CI:0.003,0.0.86; although no family history effects), with the interaction characterized by greatest impairment in the persistent distressing PLEs group. These results have implications for disentangling the importance of distress and persistence for PLEs with regards to impairments, including functional, pathophysiological, and environmental outcomes. These novel longitudinal data underscore that it is often only in the context of distress that persistent PLEs were related to impairments.

Neural vulnerability and hurricane-related media are associated with post-traumatic stress in youth

Dick, A.S., Silva, K., Gonzalez, R. et al. Neural vulnerability and hurricane-related media are associated with post-traumatic stress in youth. Nat Hum Behav 5, 1578–1589 (2021). https://doi.org/10.1038/s41562-021-01216-3

The human toll of disasters extends beyond death, injury and loss. Post-traumatic stress (PTS) can be common among directly exposed individuals, and children are particularly vulnerable. Even children far removed from harm’s way report PTS, and media-based exposure may partially account for this phenomenon. In this study, we examine this issue using data from nearly 400 9- to 11-year-old children collected before and after Hurricane Irma, evaluating whether pre-existing neural patterns moderate associations between hurricane experiences and later PTS. The ‘dose’ of both self-reported objective exposure and media exposure predicted PTS, the latter even among children far from the hurricane. Furthermore, neural responses in brain regions associated with anxiety and stress conferred particular vulnerability. For example, heightened amygdala reactivity to fearful stimuli moderated the association between self-reported media exposure and PTS. Collectively, these findings show that for some youth with measurable vulnerability, consuming extensive disaster-related media may offer an alternative pathway to disaster exposure that transcends geography and objective risk.

Widespread attenuating changes in brain connectivity associated with the general factor of psychopathology in 9- and 10-year olds

Sripada C, Angstadt M, Taxali A, Kessler D, Greathouse T, Rutherford S, Clark DA, Hyde LW, Weigard A, Brislin SJ, Hicks B, Heitzeg M. Widespread attenuating changes in brain connectivity associated with the general factor of psychopathology in 9- and 10-year olds. Transl Psychiatry. 2021 Nov 9;11(1):575. doi: 10.1038/s41398-021-01708-w. PMID: 34753911.

Convergent research identifies a general factor (“P factor”) that confers transdiagnostic risk for psychopathology. Large-scale networks are key organizational units of the human brain. However, studies of altered network connectivity patterns associated with the P factor are limited, especially in early adolescence when most mental disorders are first emerging. We studied 11,875 9- and 10-year olds from the Adolescent Brain and Cognitive Development (ABCD) study, of whom 6593 had high-quality resting-state scans. Network contingency analysis was used to identify altered interconnections associated with the P factor among 16 large-scale networks. These connectivity changes were then further characterized with quadrant analysis that quantified the directionality of P factor effects in relation to neurotypical patterns of positive versus negative connectivity across connections. The results showed that the P factor was associated with altered connectivity across 28 network cells (i.e., sets of connections linking pairs of networks); pPERMUTATION values < 0.05 FDR-corrected for multiple comparisons. Higher P factor scores were associated with hypoconnectivity within default network and hyperconnectivity between default network and multiple control networks. Among connections within these 28 significant cells, the P factor was predominantly associated with “attenuating” effects (67%; pPERMUTATION < 0.0002), i.e., reduced connectivity at neurotypically positive connections and increased connectivity at neurotypically negative connections. These results demonstrate that the general factor of psychopathology produces attenuating changes across multiple networks including default network, involved in spontaneous responses, and control networks involved in cognitive control. Moreover, they clarify mechanisms of transdiagnostic risk for psychopathology and invite further research into developmental causes of distributed attenuated connectivity.

Racism May Interrupt Age-related Brain Growth of African American Children in the United States

Assari S, Mincy R. Racism May Interrupt Age-related Brain Growth of African American Children in the United States. J Pediatr Child Health Care. 2021;6(3):1047. Epub 2021 Nov 9. PMID: 34966911; PMCID: PMC8713722.

Background: Considerable research has documented age-related growth in brain size as a marker of normal brain development. This is particularly important because brain volume has a significant role in overall cognitive performance. However, less research is done on whether age-related changes in the global brain volume differ across diverse racial and ethnic groups. We hypothesized that age-related growth in brain size would be disrupted in African American children who are historically affected by racism.

Purpose: Considering race as a proxy of racism rather than genetics, this study tested racial and ethnic differences in the effects of age on global brain volume using structural brain imaging data. Built on a sociological, rather than a biological theory, we built our study on Marginalization-related Diminished Returns (MDRs) framework, which argues that under racism, resources and assets are less effective for social groups that are historically racialized, discriminated against, marginalized, and segregated. Considering age as an asset/resource that increases the global brain volume, we expected weaker effects of age on overall brain size of African American and Hispanic children, than White and non-Hispanic children, again as a result of racism.

Methods: We borrowed the structural Magnetic Resonance Imaging (sMRI) data from the Children Brain Cognitive Development (ABCD) study, which included 9,311 9-10 year old children. The independent variable was the child’s age treated as a continuous measure (in months). The primary outcome was global brain volume. Sex, parental employment, parental education, household income, and parental marital status were the covariates. Race and ethnicity, as proxies of racism, were the moderators. To analyze the data, we used linear regression models.

Results: Age was positively associated with the global brain size in children. In line with the MDRs, the positive association between age and global brain volume was weaker for African American than White children, while family structure, sex, and family socioeconomic status was controlled.

Conclusions: Under racism, age has unequal effects on global brain size of diverse racial groups. In line with the MDRs, we observe diminished age-related growth of the brain for African American children, which documents detrimental effects of racism. For White children who are not affected by racism, age makes a large difference regarding global brain volume. Age-related growth of global brain size is diminished in African American children, whose daily lives are shaped by racism. School and residential segregation may have a role in reducing the effect of age on children’s brain growth in African American families. The results should not be interpreted as inferiority of one group but social processes that hinder normal development of a historically oppressed group.

Brain-wide functional connectivity patterns support general cognitive ability and mediate effects of socioeconomic status in youth

Sripada C, Angstadt M, Taxali A, Clark DA, Greathouse T, Rutherford S, Dickens JR, Shedden K, Gard AM, Hyde LW, Weigard A, Heitzeg M. Brain-wide functional connectivity patterns support general cognitive ability and mediate effects of socioeconomic status in youth. Transl Psychiatry. 2021 Nov 8;11(1):571. doi: 10.1038/s41398-021-01704-0. PMID: 34750359.

General cognitive ability (GCA) is an individual difference dimension linked to important academic, occupational, and health-related outcomes and its development is strongly linked to differences in socioeconomic status (SES). Complex abilities of the human brain are realized through interconnections among distributed brain regions, but brain-wide connectivity patterns associated with GCA in youth, and the influence of SES on these connectivity patterns, are poorly understood. The present study examined functional connectomes from 5937 9- and 10-year-olds in the Adolescent Brain Cognitive Development (ABCD) multi-site study. Using multivariate predictive modeling methods, we identified whole-brain functional connectivity patterns linked to GCA. In leave-one-site-out cross-validation, we found these connectivity patterns exhibited strong and statistically reliable generalization at 19 out of 19 held-out sites accounting for 18.0% of the variance in GCA scores (cross-validated partial η2). GCA-related connections were remarkably dispersed across brain networks: across 120 sets of connections linking pairs of large-scale networks, significantly elevated GCA-related connectivity was found in 110 of them, and differences in levels of GCA-related connectivity across brain networks were notably modest. Consistent with prior work, socioeconomic status was a strong predictor of GCA in this sample, and we found that distributed GCA-related brain connectivity patterns significantly statistically mediated this relationship (mean proportion mediated: 15.6%, p < 2 × 10-16). These results demonstrate that socioeconomic status and GCA are related to broad and diffuse differences in functional connectivity architecture during early adolescence, potentially suggesting a mechanism through which socioeconomic status influences cognitive development.

Pubertal Timing and Functional Neurodevelopmental Alterations Independently Mediate the Effect of Family Conflict on Adolescent Psychopathology

Petrican R, Miles S, Rudd L, Wasiewska W, Graham KS, Lawrence AD (2021). Pubertal Timing and Functional Neurodevelopmental Alterations Independently Mediate the Effect of Family Conflict on Adolescent Psychopathology, Developmental Cognitive Neuroscience, Volume 52, December 2021, 101032, 101032, ISSN 1878-9293, https://doi.org/10.1016/j.dcn.2021.101032.

This study tested the hypothesis that early life adversity (ELA) heightens psychopathology risk by concurrently altering pubertal and neurodevelopmental timing, and associated gene transcription signatures. Analyses focused on threat (family conflict/neighbourhood crime) and deprivation-related ELAs (parental inattentiveness/unmet material needs), using longitudinal data from 1514 biologically unrelated youths in the Adolescent Brain and Cognitive Development (ABCD) study. Typical developmental changes in white matter microstructure corresponded to widespread BOLD signal variability (BOLDsv) increases (linked to cell communication and biosynthesis genes) and region-specific task-related BOLDsv increases/decreases (linked to signal transduction, immune and external environmental response genes). Increasing resting-state (RS), but decreasing task-related BOLDsv predicted normative functional network segregation. Family conflict was the strongest concurrent and prospective contributor to psychopathology, while material deprivation constituted an additive risk factor. ELA-linked psychopathology was predicted by higher Time 1 threat-evoked BOLDSV (associated with axonal development, myelination, cell differentiation and signal transduction genes), reduced Time 2 RS BOLDsv (associated with cell metabolism and attention genes) and greater Time 1 to Time 2 control/attention network segregation. Earlier pubertal timing and neurodevelopmental alterations independently mediated ELA effects on psychopathology. Our results underscore the differential roles of the immediate and wider external environment(s) in concurrent and longer-term ELA consequences.

Greater radiologic evidence of hypothalamic gliosis predicts adiposity gain in children at risk for obesity

Sewaybricker LE, Kee S, Melhorn SJ, Schur EA. Greater radiologic evidence of hypothalamic gliosis predicts adiposity gain in children at risk for obesity. Obesity (Silver Spring). 2021 Nov;29(11):1770-1779. doi: 10.1002/oby.23286. PMID: 34734493.

Objective: This study investigated, in a large pediatric population, whether magnetic resonance imaging (MRI) evidence of mediobasal hypothalamic (MBH) gliosis is associated with baseline or change over 1 year in body adiposity.

Methods: Cross-sectional and prospective cohort analyses were conducted within the Adolescent Brain Cognitive Development Study. Study 1 included 169 children with usable baseline T2-weighted MRI images and anthropometrics from baseline and 1-year follow-up study visits. Signal ratios compared T2 signal intensity in MBH and two reference regions (amygdala [AMY] and putamen) as a measure of MBH gliosis. Study 2 included a distinct group of 238 children with overweight or obesity to confirm initial findings in an independent sample.

Results: In Study 1, MBH/AMY signal ratio was positively associated with BMI z score (β = 4.27, p < 0.001). A significant interaction for the association of MBH/AMY signal ratio with change in BMI z score suggested that relationships differed by baseline weight status. Study 2 found that higher MBH/AMY signal ratios associated with an increase in BMI z score for children with overweight (β = 0.58, p = 0.01), but not those with obesity (β = 0.02, p = 0.91).

Conclusions: Greater evidence of hypothalamic gliosis by MRI is associated with baseline BMI z score and predicts adiposity gain in young children at risk of obesity.

Cingulo-opercular and Cingulo-parietal Brain Networks Functional Connectivity in Pre-adolescents: Multiplicative Effects of Race, Ethnicity, and Parental Education

Assari S. Cingulo-opercular and Cingulo-parietal Brain Networks Functional Connectivity in Pre-adolescents: Multiplicative Effects of Race, Ethnicity, and Parental Education. Res Health Sci. 2021;6(2):76-99. doi: 10.22158/rhs.v6n2p76. PMID: 34734154; PMCID: PMC8562861.

Introduction: A growing body of research has shown a diminished association between socioeconomic status (SES) indicators and a wide range of neuroimaging indicators for racial and ethnic minorities compared to majority groups. However, less is known about these effects for resting-state functional connectivity between various brain networks.

Purpose: This study investigated racial and ethnic variation in the correlation between parental education and resting-state functional connectivity between the cingulo-opercular (CO) and cingulo-parietal (CP) networks in children.

Methods: This cross-sectional study used data from the Adolescent Brain Cognitive Development (ABCD) study; we analyzed the resting-state functional Magnetic Resonance Imaging (rsfMRI) data of 8,464 American pre-adolescents between the ages of 9 and 10. The main outcome measured was resting-state functional connectivity between the CO and CP networks calculated using rsfMRI. The independent variable was parental education, which was treated as a nominal variable. Age, sex, and family marital status were the study covariates. Race and ethnicity were the moderators. Mixed-effects regression models were used for data analysis, with and without interaction terms between parental education and race and ethnicity.

Results: Higher parental education was associated with higher resting-state functional connectivity between the CO and CP networks. Race and ethnicity both showed statistically significant interactions with parental education on children’s resting-state functional connectivity between CO and CP networks, suggesting that the correlation between parental education and the resting-state functional connectivity was significantly weaker for Black and Hispanic pre-adolescents compared to White and non-Hispanic pre-adolescents.

Conclusions: In line with the Minorities’ Diminished Returns theory, the association between parental education and pre-adolescents resting-state functional connectivity between CO and CP networks may be weaker in Black and Hispanic children than in White and non-Hispanic children. The weaker link between parental education and brain functional connectivity for Blacks and Hispanics than for Whites and non-Hispanics may reflect racism, racialization, and social stratification that collectively minimize the returns of SES indicators, such as parental education for non-Whites, who become others in the US.

Smaller Hippocampal Volume Among Black and Latinx Youth Living in High-Stigma Contexts

Hatzenbuehler ML, Weissman DG, McKetta S, Lattanner MR, Ford JV, Barch DM, McLaughlin KA. Smaller Hippocampal Volume Among Black and Latinx Youth Living in High-Stigma Contexts. J Am Acad Child Adolesc Psychiatry. 2021 Sep 2:S0890-8567(21)01361-7. doi: 10.1016/j.jaac.2021.08.017. Epub ahead of print. PMID: 34481917.

Objective: To determine whether structural and individual forms of stigma are associated with neurodevelopment in children.

Method: Stigma related to gender, race, and Latinx ethnicity was measured at the structural level using objective state-level indicators of social policies and prejudicial attitudes and at the individual level using self-reports of perceived discrimination. Respective associations of stigma with hippocampal volume and amygdala reactivity to threat were examined using data from the Adolescent Brain Cognitive Development (ABCD) Study (N ¼ 11,534, mean age 9.9 years), the first multisite neuroimaging study that provided substantial variability in sociopolitical contexts and that included individuallevel measures of stigma among youth.

Results: In a preregistered analysis, Black (B ¼ 58.26, p ¼ .023) and Latinx (B ¼ 40.10, p ¼ .044) youths in higher (vs lower) structural stigma contexts were found to have smaller hippocampal volume, controlling for total intracranial volume, demographics, and family socioeconomic status. This association was also observed at a trend-level among girls (p ¼ .082). The magnitude of the difference in hippocampal volume between high and low structural stigma states was equivalent to the predicted impact of a $20,000 difference in annual family income in this sample. As hypothesized, structural stigma was not associated with hippocampal volume in nonstigmatized youths, providing evidence of specificity. Perceived discrimination was unrelated to hippocampal volume in stigmatized groups. No associations between perceived discrimination or structural stigma and amygdala reactivity to threat were observed.

Conclusion: This study provides novel evidence that an objective measure of structural stigma may be more strongly related to hippocampal volume than subjective perceptions of stigma, suggesting that contextual approaches to stigma could yield new insights into neurodevelopment among marginalized youth.

Concussion Among Children in the United States General Population: Incidence and Risk Factors

Cook NE, Iverson GL. Concussion Among Children in the United States General Population: Incidence and Risk Factors. Front Neurol. 2021 Nov 1;12:773927. doi: 10.3389/fneur.2021.773927. PMID: 34790165; PMCID: PMC8591091.

The objective of this study was to examine the incidence of concussion and risk factors for sustaining concussion among children from the United States general population. This prospective cohort study used data from the Adolescent Brain Cognitive Development (ABCD) Study®. Children were recruited from schools across the US, sampled to reflect the sociodemographic variation of the US population. The current sample includes 11,013 children aged 9 to 10 years old (47.6% girls; 65.5% White) who were prospectively followed for an average of 1 year (mean = 367.9 days, SD = 40.8, range 249-601). The primary outcome was caregiver-reported concussion during a 1 year follow-up period. Logistic regression was used to determine which potential clinical, health history, and behavioral characteristics (assessed at baseline) were prospectively associated with concussion. In the 1 year follow-up period between ages 10 and 11, 1 in 100 children (n = 123, 1.1%) sustained a concussion. In univariate models, three baseline predictors (ADHD, prior concussion, and accident proneness) were significantly associated with sustaining a concussion. In a multivariate model, controlling for all other predictors, only prior concussion remained significantly associated with the occurrence of a concussion during the observation period (Odds Ratio = 5.49, 95% CI: 3.40-8.87). The most robust and only independent prospective predictor of sustaining a concussion was history of a prior concussion. History of concussion is associated with 5.5 times greater odds of sustaining concussion between ages 10 and 11 among children from the general US population.

Screen Time Use Among US Adolescents During the COVID-19 Pandemic: Findings From the Adolescent Brain Cognitive Development (ABCD) Study

Nagata JM, Cortez CA, Cattle CJ, Ganson KT, Iyer P, Bibbins-Domingo K, Baker FC. Screen Time Use Among US Adolescents During the COVID-19 Pandemic: Findings From the Adolescent Brain Cognitive Development (ABCD) Study. JAMA Pediatr. 2021 Nov 1. doi: 10.1001/jamapediatrics.2021.4334. Epub ahead of print. PMID: 34724543.

Methods
Cross-sectional data from the May 2020 COVID-19 survey (COVID-19 Rapid Response Research Release) from the Adolescent Brain Cognitive Development (ABCD) Study were analyzed. The sample consisted of 5412 adolescents predominantly aged 12 to 13 years. Centralized institutional review board approval was obtained from the University of California, San Diego. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. Written informed consent and assent were obtained from a parent or guardian and the child, respectively, to participate in the ABCD study.

Screen use for the following modalities was determined using adolescents’ self-reported hours of use on a typical day, excluding hours spent on school-related work: multiple-player gaming, single-player gaming, texting, social media, video chatting, browsing the internet, and watching or streaming movies, videos, or television shows.5 Total typical daily screen use, excluding schoolwork, was calculated as the sum. Multiple linear regression analyses estimated associations between mental health and resiliency factors (eMethods in the Supplement provides the measures) and total screen use, after adjustment for potential confounders including sex, race and ethnicity (as self-reported from a list of categories), annual household income, parent educational level, and study site. Analyses were conducted in 2021 using Stata 15.1, weighting data to approximate the American Community Survey by the US Census. Testing was 2-sided, and P < .05 was considered statistically significant.

Results
Among the 5412 adolescents included in our sample, 50.7% were female and 49.3% were male. The sample was racially and ethnically diverse (7.2% Asian; 11.1% Black; 17.2% Hispanic, Latina, and Latino; 2.5% Native American; 60.6% White; and 1.4% self-reported as other). Adolescents reported a mean (SD) of 7.70 (5.74) h/d of screen use, mostly spent on watching or streaming videos, movies, or television shows (2.42 [2.45] h/d), multiple-player gaming (1.44 [2.21] h/d), and single-player gaming (1.17 [1.82] h/d). The mean and SD screen use time for each modality by sociodemographic characteristics are given in Table 1. In adjusted models (Table 2), poorer mental health (B, 0.29; 95% CI, 0.06-0.52; P = .01) and greater perceived stress (B, 0.67; 95% CI, 0.43-0.91; P < .001) were associated with higher total screen use, while more social support (B, −0.32; 95% CI, −0.59 to −0.04; P = .02) and coping behaviors (B, −0.17; 95% CI, −0.26 to −0.09; P < .001) were associated with lower total screen use.

Discussion
In this cross-sectional study of a large, national sample of adolescents surveyed early in the COVID-19 pandemic, we found that the mean total daily screen use was 7.70 h/d. This is higher than prepandemic estimates (3.8 h/d) from the same cohort at baseline, although younger age and slightly different screen time categories could also account for differences.6 Despite the gradual reversal of quarantine restrictions, studies have suggested that screen use may remain persistently elevated.4 Screen time disparities across racial, ethnic, and income groups in adolescents have been reported previously and may be due to structural and systemic racism–driven factors (eg, built environment, access to financial resources, and digital media education)—all of which have been amplified in the COVID-19 pandemic.2 Different screen use modalities may have differential positive or negative consequences for adolescents’ well-being during the COVID-19 pandemic. Adolescents experiencing stress and poor mental health may use screens to manage negative feelings or withdraw from stressors. Although some screen modalities may be used to promote social connection, higher coping behaviors and social support in this sample were associated with lower total screen usage. Limitations of this study include the use of self-reported data. Furthermore, adolescents often multitask on screens; thus, the computed total could be an overestimate. Future studies should examine screen use trends as pandemic restrictions are lifted and also explore mechanisms to prevent sociodemographic disparities.

Demographic and Mental Health Assessments in the Adolescent Brain and Cognitive Development Study: Updates and Age-Related Trajectories

Deanna M. Barch, Matthew D. Albaugh, Arielle Baskin-Sommers, Brittany E. Bryant, Duncan B. Clark, Anthony Steven Dick, Eric Feczko, John J. Foxe, Dylan G. Gee, Jay Giedd, Meyer D. Glantz, James J. Hudziak, Nicole R. Karcher, Kimberly LeBlanc, Melanie Maddox, Erin C. McGlade, Carrie Mulford, Bonnie J. Nagel, Gretchen Neigh, Clare E Palmer, Alexandra S. Potter, Kenneth J. Sher, Susan F. Tapert, Wesley K. Thompson, Laili Xie (2021). Demographic and Mental Health Assessments in the Adolescent Brain and Cognitive Development Study: Updates and Age-Related Trajectories, Developmental Cognitive Neuroscience, Volume 52, December 2021, 101031, ISSN 1878-9293, https://doi.org/10.1016/j.dcn.2021.101031.

The Adolescent Brain Cognitive Development (ABCD) Study of 11,880 youth incorporates a comprehensive range of measures assessing predictors and outcomes related to mental health across childhood and adolescence in participating youth, as well as information about family mental health history. We have previously described the logic and content of the mental health assessment battery at Baseline and 1-year follow-up. Here, we describe changes to that battery and issues and clarifications that have emerged, as well as additions to the mental health battery at the 2-, 3-, 4-, and 5-year follow-ups. We capitalize on the recent release of longitudinal data for caregiver and youth report of mental health data to evaluate trajectories of dimensions of psychopathology as a function of demographic factors. For both caregiver and self-reported mental health symptoms, males showed age-related decreases in internalizing and externalizing symptoms, while females showed an increase in internalizing symptoms with age. Multiple indicators of socioeconomic status (caregiver education, family income, financial adversity, neighborhood poverty) accounted for unique variance in both caregiver and youth-reported externalizing and internalizing symptoms. These data highlight the importance of examining developmental trajectories of mental health as a function of key factors such as sex and socioeconomic environment.

Contributions of PTSD polygenic risk and environmental stress to suicidality in preadolescents

Daskalakis NP, Schultz LM, Visoki E, Moore TM, Argabright ST, Harnett NG, DiDomenico GE, Warrier V, Almasy L, Barzilay R. Contributions of PTSD polygenic risk and environmental stress to suicidality in preadolescents. Neurobiol Stress. 2021 Oct 27;15:100411. doi: 10.1016/j.ynstr.2021.100411. PMID: 34765698; PMCID: PMC8569631.

Suicidal ideation and attempts (i.e., suicidality) are complex behaviors driven by environmental stress, genetic susceptibility, and their interaction. Preadolescent suicidality is a major health problem with rising rates, yet its underlying biology is understudied. Here we studied effects of genetic stress susceptibility, approximated by the polygenic risk score (PRS) for post-traumatic-stress-disorder (PTSD), on preadolescent suicidality in participants from the Adolescent Brain Cognitive Development (ABCD) Study®. We further evaluated PTSD-PRS effects on suicidality in the presence of environmental stressors that are established suicide risk factors. Analyses included both European and African ancestry participants using PRS calculated based on summary statistics from ancestry-specific genome-wide association studies. In European ancestry participants (N = 4,619, n = 378 suicidal), PTSD-PRS was associated with preadolescent suicidality (odds ratio [OR] = 1.12, 95%CI 1-1.25, p = 0.038). Results in African ancestry participants (N = 1,334, n = 130 suicidal) showed a similar direction but were not statistically significant (OR = 1.21, 95%CI 0.93-1.57, p = 0.153). Sensitivity analyses using non-psychiatric polygenic score for height and using cross-ancestry PTSD-PRS did not reveal any association with suicidality, supporting the specificity of the association of ancestry-specific PTSD-PRS with suicidality. Environmental stressors were robustly associated with suicidality across ancestries with moderate effect size for negative life events and family conflict (OR 1.27-1.6); and with large effect size (OR ∼ 4) for sexual-orientation discrimination. When combined with environmental factors, PTSD-PRS showed marginal additive effects in explaining variability in suicidality, with no evidence for G × E interaction. Results support use of cross-phenotype PRS, specifically stress-susceptibility, as a genetic marker for suicidality risk early in the lifespan.

Shorter Duration and Lower Quality Sleep Have Widespread Detrimental Effects on Developing Functional Brain Networks in Early Adolescence

Skylar J Brooks, Eliot S Katz, Catherine Stamoulis, Shorter Duration and Lower Quality Sleep Have Widespread Detrimental Effects on Developing Functional Brain Networks in Early Adolescence, Cerebral Cortex Communications, 2021; tgab062, https://doi.org/10.1093/texcom/tgab062

Sleep is critical for cognitive health, especially during complex developmental periods such as adolescence. However, its effects on maturating brain networks that support cognitive function are only partially understood. We investigated the impact of shorter duration and reduced quality sleep, common stressors during development, on functional network properties in early adolescence—a period of significant neural maturation, using resting-state fMRI from 5566 children (median age = 120.0 months; 52.1% females) in the Adolescent Brain Cognitive Development (ABCD) cohort. Decreased sleep duration, increased sleep latency, frequent waking up at night, and sleep-disordered breathing symptoms were associated with lower topological efficiency, flexibility, and robustness of visual, sensorimotor, attention, fronto-parietal control, default-mode and/or limbic networks, and with aberrant changes in the thalamus, basal ganglia, hippocampus and cerebellum (p < 0.05). These widespread effects, many of which were BMI-independent, suggest that unhealthy sleep in early adolescence may impair neural information processing and integration across incompletely developed networks, potentially leading to deficits in their cognitive correlates, including attention, reward, emotion processing and regulation, memory, and executive control. Shorter sleep duration, frequent snoring, difficulty waking up and daytime sleepiness had additional detrimental network effects in non-white participants, indicating racial disparities in the influence of sleep metrics.

Large-scale functional brain networks of maladaptive childhood aggression identified by connectome-based predictive modeling

Ibrahim K, Noble S, He G, Lacadie C, Crowley MJ, McCarthy G, Scheinost D, Sukhodolsky DG. Large-scale functional brain networks of maladaptive childhood aggression identified by connectome-based predictive modeling. Mol Psychiatry. 2021 Oct 25. doi: 10.1038/s41380-021-01317-5. Epub ahead of print. PMID: 34690348.

Disruptions in frontoparietal networks supporting emotion regulation have been long implicated in maladaptive childhood aggression. However, the association of connectivity between large-scale functional networks with aggressive behavior has not been tested. The present study examined whether the functional organization of the connectome predicts severity of aggression in children. This cross-sectional study included a transdiagnostic sample of 100 children with aggressive behavior (27 females) and 29 healthy controls without aggression or psychiatric disorders (13 females). Severity of aggression was indexed by the total score on the parent-rated Reactive-Proactive Aggression Questionnaire. During fMRI, participants completed a face emotion perception task of fearful and calm faces. Connectome-based predictive modeling with internal cross-validation was conducted to identify brain networks that predicted aggression severity. The replication and generalizability of the aggression predictive model was then tested in an independent sample of children from the Adolescent Brain Cognitive Development (ABCD) study. Connectivity predictive of aggression was identified within and between networks implicated in cognitive control (medial-frontal, frontoparietal), social functioning (default mode, salience), and emotion processing (subcortical, sensorimotor) (r = 0.31, RMSE = 9.05, p = 0.005). Out-of-sample replication (p < 0.002) and generalization (p = 0.007) of findings predicting aggression from the functional connectome was demonstrated in an independent sample of children from the ABCD study (n = 1791; n = 1701). Individual differences in large-scale functional networks contribute to variability in maladaptive aggression in children with psychiatric disorders. Linking these individual differences in the connectome to variation in behavioral phenotypes will advance identification of neural biomarkers of maladaptive childhood aggression to inform targeted treatments.

Associations of Family Distress, Family Income, and Acculturation on Pediatric Cognitive Performance Using the NIH Toolbox: Implications for Clinical and Research Settings

Thompson RC, Montena AL, Liu K, Watson J, Warren SL. Associations of Family Distress, Family Income, and Acculturation on Pediatric Cognitive Performance Using the NIH Toolbox: Implications for Clinical and Research Settings. Arch Clin Neuropsychol. 2021 Oct 19:acab082. doi: 10.1093/arclin/acab082. Epub ahead of print. PMID: 34664626.

Objective: There is a growing recognition that the use of conventional norms (e.g., age, sex, years of education, race) as proxies to capture a broad range of sociocultural variability on cognitive performance is suboptimal, limiting sample representativeness. The present study evaluated the incremental utility of family income, family conflict, and acculturation beyond the established associations of age, gender,maternal years of education, and race on cognitive performance.

Method: Hierarchical linear regressions evaluated the incremental utility of sociocultural factors on National Institutes of Health Toolbox in a nationally representative sample of pre-adolescent children (n = 11,878; Mage = 10.0 years; Adolescent Brain Cognitive Development Study). A regression-based norming procedure was implemented for significant models. Paired sample t-tests were used to compare original and newly created demographically corrected T-scores.

Results: Nearly all regression models predicted performance on the NIH-TB subtests and composite scores (p < .005). Greater family income and lower family conflict predicted better performance, although the effect sizes were small by traditional standards. Acculturation scores did not explain additional variance in cognitive performance. Lastly, there were no significant differences between the original and newly created demographically corrected T-scores (Mdiff < 0.50).

Conclusions: The present study highlights that, although family income, family conflict, and acculturation have been shown to routinely influence cognitive performance in preadolescent children, the NIH-TB appears to be highly robust to individual differences in sociocultural factors in children between ages 9 and 10. Contextual and temporal implications of the present results are discussed.

Passive Sensing of Preteens’ Smartphone Use: An Adolescent Brain Cognitive Development (ABCD) Cohort Substudy

Wade N, Ortigara JM, Sullivan RM, Tomko RL, Breslin FJ, Baker FC, Fuemmeler BF, Delrahim Howlett K, Lisdahl KM, Marshall AT, Mason MJ, Neale MC, Squeglia LM, Wolff-Hughes DL, Tapert SF, Bagot KS; ABCD Novel Technologies Workgroup. Passive Sensing of Preteens’ Smartphone Use: An Adolescent Brain Cognitive Development (ABCD) Cohort Substudy. JMIR Ment Health. 2021 Oct 18;8(10):e29426. doi: 10.2196/29426. PMID: 34661541.

Background: Concerns abound regarding childhood smartphone use, but studies to date have largely relied on self-reported screen use. Self-reporting of screen use is known to be misreported by pediatric samples and their parents, limiting the accurate determination of the impact of screen use on social, emotional, and cognitive development. Thus, a more passive, objective measurement of smartphone screen use among children is needed.

Objective: This study aims to passively sense smartphone screen use by time and types of apps used in a pilot sample of children and to assess the feasibility of passive sensing in a larger longitudinal sample.

Methods: The Adolescent Brain Cognitive Development (ABCD) study used passive, objective phone app methods for assessing smartphone screen use over 4 weeks in 2019-2020 in a subsample of 67 participants (aged 11-12 years; 31/67, 46% female; 23/67, 34% White). Children and their parents both reported average smartphone screen use before and after the study period, and they completed a questionnaire regarding the acceptability of the study protocol. Descriptive statistics for smartphone screen use, app use, and protocol feasibility and acceptability were reviewed. Analyses of variance were run to assess differences in categorical app use by demographics. Self-report and parent report were correlated with passive sensing data.

Results: Self-report of smartphone screen use was partly consistent with objective measurement (r=0.49), although objective data indicated that children used their phones more than they reported. Passive sensing revealed the most common types of apps used were for streaming (mean 1 hour 57 minutes per day, SD 1 hour 32 minutes), communication (mean 48 minutes per day, SD 1 hour 17 minutes), gaming (mean 41 minutes per day, SD 41 minutes), and social media (mean 36 minutes per day, SD 1 hour 7 minutes). Passive sensing of smartphone screen use was generally acceptable to children (43/62, 69%) and parents (53/62, 85%).

Conclusions: The results of passive, objective sensing suggest that children use their phones more than they self-report. Therefore, use of more robust methods for objective data collection is necessary and feasible in pediatric samples. These data may then more accurately reflect the impact of smartphone screen use on behavioral and emotional functioning. Accordingly, the ABCD study is implementing a passive sensing protocol in the full ABCD cohort. Taken together, passive assessment with a phone app provided objective, low-burden, novel, informative data about preteen smartphone screen use.

An Update on the Assessment of Culture and Environment in the ABCD Study®: Emerging Literature and Protocol Updates over Three Measurement Waves

Gonzalez R, Thompson EL, Sanchez M, Morris A, Gonzalez MR, Feldstein Ewing SW, Mason MJ, Arroyo J, Howlett K, Tapert SF, Zucker RA (2021).  An Update on the Assessment of Culture and Environment in the ABCD Study®: Emerging Literature and Protocol Updates over Three Measurement Waves. Developmental Cognitive Neuroscience, Volume 52, December 2021, 101021, ISSN 1878-9293, https://doi.org/10.1016/j.dcn.2021.101021.

Advances in our understanding of risk and resilience factors in adolescent brain health and development increasingly demand a broad set of assessment tools that consider a youth’s peer, family, school, neighborhood, and cultural contexts in addition to neurobiological, genetic, and biomedical information. The Culture and Environment (CE) Workgroup (WG) of the Adolescent Brain Cognitive Development (ABCD) Study curates these important components of the protocol throughout ten years of planned data collection. In this report, the CE WG presents an update on the evolution of the ABCD Study® CE protocol since study inception (Zucker et al., 2018), as well as emerging findings that include CE measures. Background and measurement characteristics of instruments present in the study since baseline have already been described in our 2018 report, and therefore are only briefly described here. New measures introduced since baseline are described in more detail. Descriptive statistics on all measures are presented based on a total sample of 11,000+ youth and their caregivers assessed at baseline and the following two years. Psychometric properties of the measures, including longitudinal aspects of the data, are reported, along with considerations for future measurement waves. The CE WG ABCD® components are an essential part of the overall protocol that permits characterization of the unique cultural and social environment within which each developing brain is transactionally embedded.

Associations Among Negative Life Events, Changes in Cortico-Limbic Connectivity, and Psychopathology in the ABCD Study

Brieant AE, Sisk LM, Gee DG (2021). Associations Among Negative Life Events, Changes in Cortico-Limbic Connectivity, and Psychopathology in the ABCD Study. Developmental Cognitive Neuroscience. Available online 16 October 2021, 101022. Volume 52, December 2021, 101022. https://doi.org/10.1016/j.dcn.2021.101022.

Adversity exposure is a risk factor for psychopathology, which most frequently onsets during adolescence, and prior research has demonstrated that alterations in cortico-limbic connectivity may account in part for this association. In a sample of youth from the Adolescent Brain Cognitive Development (ABCD) Study (N = 4006), we tested a longitudinal structural equation model to examine the indirect effect of adversity exposure (negative life events) on later psychopathology via changes in cortico-limbic resting-state functional connectivity (rsFC). We also examined the potential protective effects of parental acceptance. Generally, cortico-limbic connectivity became more strongly negative between baseline and year 2 follow-up, suggesting that stronger negative correlations within these cortico-limbic networks may reflect a more mature phenotype. Exposure to a greater number of negative life events was associated with stronger negative cortico-limbic rsFC which, in turn, was associated with lower internalizing (but not externalizing) symptoms. The indirect effect of negative life events on internalizing symptoms via cortico-limbic rsFC was significant. Parental acceptance did not moderate the association between negative life events and rsFC. Our findings highlight how stressful childhood experiences may accelerate neurobiological maturation in specific cortico-limbic connections, potentially reflecting an adaptive process that protects against internalizing problems in the context of adversity.

Association between parental age, brain structure, and behavioral and cognitive problems in children

Du J, Rolls ET, Gong W, Cao M, Vatansever D, Zhang J, Kang J, Cheng W, Feng J. Association between parental age, brain structure, and behavioral and cognitive problems in children. Mol Psychiatry. 2021 Oct 14. doi: 10.1038/s41380-021-01325-5. Epub ahead of print. PMID: 34650205.

Objective: To investigate the relation between parental age, and behavioral, cognitive and brain differences in the children.

Method: Data with children aged 9-11 of 8709 mothers with parental age 15-45 years were analyzed from the Adolescent Brain Cognitive Development (ABCD) study. A general linear model was used to test the associations of the parental age with brain structure, and behavioral and cognitive problems scores.

Results: Behavioral and cognitive problems were greater in the children of the younger mothers, and were associated with lower volumes of cortical regions in the children. There was a linear correlation between the behavioral and cognitive problems scores, and the lower brain volumes (r > 0.6), which was evident when parental age was included as a stratification factor. The regions with lower volume included the anterior cingulate cortex, medial and lateral orbitofrontal cortex and amygdala, parahippocampal gyrus and hippocampus, and temporal lobe (FDR corrected p < 0.01). The lower cortical volumes and areas in the children significantly mediated the association between the parental age and the behavioral and cognitive problems in the children (all p < 10-4). The effects were large, such as the 71.4% higher depressive problems score, and 27.5% higher rule-breaking score, in the children of mothers aged 15-19 than the mothers aged 34-35.

Conclusions: Lower parental age is associated with behavioral problems and reduced cognitive performance in the children, and these differences are related to lower volumes and areas of some cortical regions which mediate the effects in the children. The findings are relevant to psychiatric understanding and assessment.

Risk of lead exposure, subcortical brain structure, and cognition in a large cohort of 9- to 10-year-old children

Marshall AT, McConnell R, Lanphear BP, Thompson WK, Herting MM, Sowell ER. Risk of lead exposure, subcortical brain structure, and cognition in a large cohort of 9- to 10-year-old children. PLoS One. 2021 Oct 14;16(10):e0258469. doi: 10.1371/journal.pone.0258469. PMID: 34648580.

Adolescent civic engagement: Lessons from Black Lives Matter

Baskin-Sommers A, Simmons C, Conley M, Chang SA, Estrada S, Collins M, Pelham W, Beckford E Mitchell-Adams H, Berrian N, Tapert SF, Gee DG, Casey BJ. Adolescent civic engagement: Lessons from Black Lives Matter. PNAS October 12, 2021 118 (41) e2109860118; https://doi.org/10.1073/pnas.2109860118.

In 2020, individuals of all ages engaged in demonstrations condemning police brutality and supporting the Black Lives Matter (BLM) movement. Research that used parent reports and trends commented on in popular media suggested that adolescents under 18 had become increasingly involved in this movement. In the first large-scale quantitative survey of adolescents’ exposure to BLM demonstrations, 4,970 youth (meanage = 12.88 y) across the United States highlighted that they were highly engaged, particularly with media, and experienced positive emotions when exposed to the BLM movement. In addition to reporting strong engagement and positive emotions related to BLM demonstrations, Black adolescents in particular reported higher negative emotions when engaging with different types of media and more exposure to violence during in-person BLM demonstrations. Appreciating youth civic engagement, while also providing support for processing complex experiences and feelings, is important for the health and welfare of young people and society.

A Comprehensive Overview of the Physical Health of the Adolescent Brain Cognitive Development Study Cohort at Baseline

Palmer CE, Sheth C, Marshall AT, Adise S, Baker FC, Chang L, Clark DB, Coronado C, Dagher RK, Diaz V, Dowling GJ, Gonzalez MR, Haist F, Herting MM, Huber RS, Jernigan TL, LeBlanc K, Lee K, Lisdahl KM, Neigh G, Patterson MW, Renshaw P, Rhee KE, Tapert S, Thompson WK, Uban K, Sowell ER, Yurgelun-Todd D. A Comprehensive Overview of the Physical Health of the Adolescent Brain Cognitive Development Study Cohort at Baseline. Front Pediatr. 2021 Oct 5;9:734184. doi: 10.3389/fped.2021.734184. PMID: 34692610; PMCID: PMC8526338.

Physical health in childhood is crucial for neurobiological as well as overall development, and can shape long-term outcomes into adulthood. The landmark, longitudinal Adolescent Brain Cognitive Development StudySM (ABCD study®), was designed to investigate brain development and health in almost 12,000 youth who were recruited when they were 9-10 years old and will be followed through adolescence and early adulthood. The overall goal of this paper is to provide descriptive analyses of physical health measures in the ABCD study at baseline, including but not limited to sleep, physical activity and sports involvement, and body mass index. Further this summary will describe how physical health measures collected from the ABCD cohort compare with current normative data and clinical guidelines. We propose this data set has the potential to facilitate clinical recommendations and inform national standards of physical health in this age group. This manuscript will also provide important information for ABCD users and help guide analyses investigating physical health including new avenues for health disparity research as it pertains to adolescent and young adult development.

Recalibrating expectations about effect size: A multi-method survey of effect sizes in the ABCD study

Owens MM, Potter A, Hyatt CS, Albaugh M, Thompson WK, Jernigan T, Yuan D, Hahn S, Allgaier N, Garavan H. Recalibrating expectations about effect size: A multi-method survey of effect sizes in the ABCD study. PLoS One. 2021 Sep 23;16(9):e0257535. doi: 10.1371/journal.pone.0257535. PMID: 34555056.

Effect sizes are commonly interpreted using heuristics established by Cohen (e.g., small: r = .1, medium r = .3, large r = .5), despite mounting evidence that these guidelines are mis-calibrated to the effects typically found in psychological research. This study’s aims were to 1) describe the distribution of effect sizes across multiple instruments, 2) consider factors qualifying the effect size distribution, and 3) identify examples as benchmarks for various effect sizes. For aim one, effect size distributions were illustrated from a large, diverse sample of 9/10-year-old children. This was done by conducting Pearson’s correlations among 161 variables representing constructs from all questionnaires and tasks from the Adolescent Brain and Cognitive Development Study® baseline data. To achieve aim two, factors qualifying this distribution were tested by comparing the distributions of effect size among various modifications of the aim one analyses. These modified analytic strategies included comparisons of effect size distributions for different types of variables, for analyses using statistical thresholds, and for analyses using several covariate strategies. In aim one analyses, the median in-sample effect size was .03, and values at the first and third quartiles were .01 and .07. In aim two analyses, effects were smaller for associations across instruments, content domains, and reporters, as well as when covarying for sociodemographic factors. Effect sizes were larger when thresholding for statistical significance. In analyses intended to mimic conditions used in “real-world” analysis of ABCD data, the median in-sample effect size was .05, and values at the first and third quartiles were .03 and .09. To achieve aim three, examples for varying effect sizes are reported from the ABCD dataset as benchmarks for future work in the dataset. In summary, this report finds that empirically determined effect sizes from a notably large dataset are smaller than would be expected based on existing heuristics.

Covariate Correcting Networks for Identifying Associations Between Socioeconomic Factors and Brain Outcomes in Children

Cho H., Park G., Isaiah A., Kim W.H. (2021) Covariate Correcting Networks for Identifying Associations Between Socioeconomic Factors and Brain Outcomes in Children. In: de Bruijne M. et al. (eds) Medical Image Computing and Computer Assisted Intervention – MICCAI 2021. MICCAI 2021. Lecture Notes in Computer Science, vol 12907. Springer, Cham. https://doi.org/10.1007/978-3-030-87234-2_40

Brain development in adolescence is synthetically influenced by various factors such as age, education, and socioeconomic conditions. To identify an independent effect from a variable of interest (e.g., socioeconomic conditions), statistical models such as General Linear Model (GLM) are typically adopted to account for covariates (e.g., age and gender). However, statistical models may be vulnerable with insufficient sample size and outliers, and multiple tests for a whole brain analysis lead to inevitable false-positives without sufficient sensitivity. Hence, it is necessary to develop a unified framework for multiple tests that robustly fits the observation and increases sensitivity. We therefore propose a unified flexible neural network that optimizes on the contribution from the main variable of interest as introduced in original GLM, which leads to improved statistical outcomes. The results on group analysis with fractional anisotropy (FA) from Diffusion Tensor Images from Adolescent Brain Cognitive Development (ABCD) study demonstrate that the proposed method provides much more selective and meaningful detection of ROIs related to socioeconomic status over conventional methods.

Prevalence and correlates of suicidal ideation and suicide attempts in preadolescent children: A US population-based study

Lawrence HR, Burke TA, Sheehan AE, Pastro B, Levin RY, Walsh RFL, Bettis AH, Liu RT. Prevalence and correlates of suicidal ideation and suicide attempts in preadolescent children: A US population-based study. Transl Psychiatry 11, 489 (2021). https://doi.org/10.1038/s41398-021-01593-3.

The present study evaluated sociodemographic and diagnostic predictors of suicidal ideation and attempts in a nationally representative sample of preadolescent youth enrolled in the Adolescent Brain Cognitive Development Study. Rates and predictors of psychiatric treatment utilization among suicidal youth also were examined. Eleven thousand eight hundred and seventy-five 9- and 10-year-old children residing in the United States were assessed. Children and their parents/guardians provided reports of children’s lifetime history of suicidal ideation, suicide attempts, and psychiatric disorders. Parents also reported on sociodemographic characteristics and mental health service utilization. Multivariate logistic regression analyses were employed to evaluate sociodemographic and diagnostic correlates of suicidal ideation, suicide attempts among youth with suicidal ideation, and treatment utilization among youth with suicidal ideation and suicide attempts. Lifetime prevalence rates were 14.33% for suicidal ideation and 1.26% for suicide attempts. Youth who identified as male, a sexual minority, or multiracial had greater odds of suicidal ideation, and sexual minority youth and youth with a low family income had greater odds of suicide attempts. Comorbid psychopathology was associated with higher odds of both suicidal ideation and suicide attempts. In youth, 34.59% who have suicidal ideation and 54.82% who had attempted suicide received psychiatric treatment. Treatment utilization among suicidal youth was lower among those who identified as female, Black, and Hispanic. Suicidal ideation and attempts among preadolescent children are concerningly high and targeted assessment and preventative efforts are needed, especially for males, racial, ethnic, and sexual minority youth, and those youth experiencing comorbidity.

Vertex-wise multivariate genome-wide association study identifies 780 unique genetic loci associated with cortical morphology

Shadrin AA, Kaufmann T, van der Meer D, Palmer CE, Makowski C, Loughnan R, Jernigan TL, Seibert TM, Hagler DJ, Smeland OB, Motazedi E, Chu Y, Lin A, Cheng W, Hindley G, Thompson WK, Fan CC, Holland D, Westlye LT, Frei O, Andreassen OA, Dale AM. Vertex-wise multivariate genome-wide association study identifies 780 unique genetic loci associated with cortical morphology. Neuroimage. 2021 Sep 21;244:118603. doi: 10.1016/j.neuroimage.2021.118603. Epub ahead of print. PMID: 34560273.

Brain morphology has been shown to be highly heritable, yet only a small portion of the heritability is explained by the genetic variants discovered so far. Here we extended the Multivariate Omnibus Statistical Test (MOSTest) and applied it to genome-wide association studies (GWAS) of vertex-wise structural magnetic resonance imaging (MRI) cortical measures from N=35,657 participants in the UK Biobank. We identified 695 loci for cortical surface area and 539 for cortical thickness, in total 780 unique genetic loci associated with cortical morphology robustly replicated in 8,060 children of mixed ethnicity from the Adolescent Brain Cognitive Development (ABCD) Study®. This reflects more than 8-fold increase in genetic discovery at no cost to generalizability compared to the commonly used univariate GWAS methods applied to region of interest (ROI) data. Functional follow up including gene-based analyses implicated 10% of all protein-coding genes and pointed towards pathways involved in neurogenesis and cell differentiation. Power analysis indicated that applying the MOSTest to vertex-wise structural MRI data triples the effective sample size compared to conventional univariate GWAS approaches. The large boost in power obtained with the vertex-wise MOSTest together with pronounced replication rates and highlighted biologically meaningful pathways underscores the advantage of multivariate approaches in the context of highly distributed polygenic architecture of the human brain.

Identifying profiles of brain structure and associations with current and future psychopathology in youth

Mattoni M, Wilson S, Olino T. Identifying profiles of brain structure and associations with current and future psychopathology in youth. Developmental Cognitive Neuroscience, Volume 51, October 2021, 101013, https://doi.org/10.1016/j.dcn.2021.101013.

Brain structure is often studied as a marker of youth psychopathology by examining associations between volume or thickness of individual regions and specific diagnoses. However, these univariate approaches do not address whether the effect of a particular region may depend on the structure of other regions. Here, we identified subgroups of individuals with distinct profiles of brain structure and examined how these profiles were associated with concurrent and future youth psychopathology. We used latent profile analysis to identify distinct neuroanatomical profiles of subcortical region volume and orbitofrontal cortical thickness in the ABCD study (N = 9376, mean age = 9.91, SD = 0.62). We identified a five-profile solution consisting of a reduced subcortical volume profile, a reduced orbitofrontal thickness profile, a reduced limbic and elevated striatal volume profile, an elevated orbitofrontal thickness and reduced striatal volume profile, and an elevated orbitofrontal thickness and subcortical volume profile. While controlling for age, sex, and intracranial volume, profiles exhibited differences in concurrent psychopathology measured dimensionally and categorically and in psychopathology at 1-year follow-up measured dimensionally. Results show that profiles of brain structure have incremental validity for associations with youth psychopathology beyond intracranial volume.

Sleep Disturbances, Obesity, and Cognitive Function in Childhood: A Mediation Analysis

Mattey-Mora PP, Nelson EJ. Sleep Disturbances, Obesity, and Cognitive Function in Childhood: A Mediation Analysis. Curr Dev Nutr. 2021 Sep 15;5(10):nzab119. doi: 10.1093/cdn/nzab119. PMID: 34661044; PMCID: PMC8513758.

Background: Childhood cognitive development is influenced by biological and environmental factors. One such factor, obesity, impairs cognitive development and is associated with sleep disturbances.

Objectives: We aimed to examine the mediating role of sleep disturbances on the relation between BMI and cognitive function in children.

Methods: A total of 9951 children aged 9-10 y were included in this cross-sectional study. Children were recruited from the longitudinal ABCD (Adolescent Brain Cognitive Development) Study. Cognitive development was assessed using metrics for fluid, crystallized, and total cognitive function. Mediation analyses were conducted via linear regression modeling, with adjustment for potential confounders (sex, age, ethnicity, household income, parental education, and self-reported physical activity) for each of the 3 outcomes. Mediation significance was determined by bootstrapping.

Results: A statistically significant inverse association was found between BMI and total (β = -0.41, P < 0.001) and fluid (β = -0.49, P < 0.001) cognition, but not for crystallized cognition. Total sleep disturbances partially mediated the association between BMI and fluid cognition (indirect effect: -0.02, P = 0.002; proportion of the total effect: 0.05, P = 0.002), but no mediation was found in the association between BMI and total cognition.

Conclusions: Sleep disturbances partially mediate the effect of childhood obesity on cognitive function, particularly in fluid cognitions. Future work is necessary to understand the effects of sleep disturbances and obesity on reduced childhood cognition throughout time, predominantly across the life course.

Multimodal MR Images-Based Diagnosis of Early Adolescent Attention-Deficit/Hyperactivity Disorder Using Multiple Kernel Learning

Zhou X, Lin Q, Gui Y, Wang Z, Liu M, Lu H. Multimodal MR Images-Based Diagnosis of Early Adolescent Attention-Deficit/Hyperactivity Disorder Using Multiple Kernel Learning. Front Neurosci. 2021 Sep 14;15:710133. doi: 10.3389/fnins.2021.710133. PMID: 34594183; PMCID: PMC8477011.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common brain diseases among children. The current criteria of ADHD diagnosis mainly depend on behavior analysis, which is subjective and inconsistent, especially for children. The development of neuroimaging technologies, such as magnetic resonance imaging (MRI), drives the discovery of brain abnormalities in structure and function by analyzing multimodal neuroimages for computer-aided diagnosis of brain diseases. This paper proposes a multimodal machine learning framework that combines the Boruta based feature selection and Multiple Kernel Learning (MKL) to integrate the multimodal features of structural and functional MRIs and Diffusion Tensor Images (DTI) for the diagnosis of early adolescent ADHD. The rich and complementary information of the macrostructural features, microstructural properties, and functional connectivities are integrated at the kernel level, followed by a support vector machine classifier for discriminating ADHD from healthy children. Our experiments were conducted on the comorbidity-free ADHD subjects and covariable-matched healthy children aged 9-10 chosen from the Adolescent Brain and Cognitive Development (ABCD) study. This paper is the first work to combine structural and functional MRIs with DTI for early adolescents of the ABCD study. The results indicate that the kernel-level fusion of multimodal features achieves 0.698 of AUC (area under the receiver operating characteristic curves) and 64.3% of classification accuracy for ADHD diagnosis, showing a significant improvement over the early feature fusion and unimodal features. The abnormal functional connectivity predictors, involving default mode network, attention network, auditory network, and sensorimotor mouth network, thalamus, and cerebellum, as well as the anatomical regions in basal ganglia, are found to encode the most discriminative information, which collaborates with macrostructure and diffusion alterations to boost the performances of disorder diagnosis.

Genetic variation in endocannabinoid signaling is associated with differential network-level functional connectivity in youth

Sisk LM, Rapuano KM, Conley MI, Greene AS, Horien C, Rosenberg MD, Scheinost D, Constable RT, Glatt CE, Casey BJ, Gee DG. Genetic variation in endocannabinoid signaling is associated with differential network-level functional connectivity in youth. J Neurosci Res. 2021 Sep 8. doi: 10.1002/jnr.24946. Epub ahead of print. PMID: 34496065.

The endocannabinoid system is an important regulator of emotional responses such as fear, and a number of studies have implicated endocannabinoid signaling in anxiety. The fatty acid amide hydrolase (FAAH) C385A polymorphism, which is associated with enhanced endocannabinoid signaling in the brain, has been identified across species as a potential protective factor from anxiety. In particular, adults with the variant FAAH 385A allele have greater fronto-amygdala connectivity and lower anxiety symptoms. Whether broader network-level differences in connectivity exist, and when during development this neural phenotype emerges, remains unknown and represents an important next step in understanding how the FAAH C385A polymorphism impacts neurodevelopment and risk for anxiety disorders. Here, we leveraged data from 3,109 participants in the nationwide Adolescent Brain Cognitive Development Study℠ (10.04 ± 0.62 years old; 44.23% female, 55.77% male) and a cross-validated, data-driven approach to examine associations between genetic variation and large-scale resting-state brain networks. Our findings revealed a distributed brain network, comprising functional connections that were both significantly greater (95% CI for p values = [<0.001, <0.001]) and lesser (95% CI for p values = [0.006, <0.001]) in A-allele carriers relative to non-carriers. Furthermore, there was a significant interaction between genotype and the summarized connectivity of functional connections that were greater in A-allele carriers, such that non-carriers with connectivity more similar to A-allele carriers (i.e., greater connectivity) had lower anxiety symptoms (β = -0.041, p = 0.030). These findings provide novel evidence of network-level changes in neural connectivity associated with genetic variation in endocannabinoid signaling and suggest that genotype-associated neural differences may emerge at a younger age than genotype-associated differences in anxiety.

Screen time and early adolescent mental health, academic, and social outcomes in 9- and 10- year old children: Utilizing the Adolescent Brain Cognitive Development ℠ (ABCD) Study

Paulich KN, Ross JM, Lessem JM, Hewitt JK. Screen time and early adolescent mental health, academic, and social outcomes in 9- and 10- year old children: Utilizing the Adolescent Brain Cognitive Development ℠ (ABCD) Study. PLoS One. 2021 Sep 8;16(9):e0256591. doi: 10.1371/journal.pone.0256591. PMID: 34496002.

In a technology-driven society, screens are being used more than ever. The high rate of electronic media use among children and adolescents begs the question: is screen time harming our youth? The current study draws from a nationwide sample of 11,875 participants in the United States, aged 9 to 10 years, from the Adolescent Brain Cognitive Development Study (ABCD Study®). We investigate relationships between screen time and mental health, behavioral problems, academic performance, sleep habits, and peer relationships by conducting a series of correlation and regression analyses, controlling for SES and race/ethnicity. We find that more screen time is moderately associated with worse mental health, increased behavioral problems, decreased academic performance, and poorer sleep, but heightened quality of peer relationships. However, effect sizes associated with screen time and the various outcomes were modest; SES was more strongly associated with each outcome measure. Our analyses do not establish causality and the small effect sizes observed suggest that increased screen time is unlikely to be directly harmful to 9-and-10-year-old children.

Associations Between Neighborhood Disadvantage, Resting-State Functional Connectivity, and Behavior in the Adolescent Brain Cognitive Development Study: The Moderating Role of Positive Family and School Environments

Rakesh D, Seguin C, Zalesky A, Cropley V, Whittle S. Associations between neighborhood disadvantage, resting-state functional connectivity, and behavior in the Adolescent Brain Cognitive Development (ABCD) Study: Moderating role of positive family and school environments. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Volume 6, Issue 9, September 2021, Pages 877-886. https://doi.org/10.1016/j.bpsc.2021.03.008

Background
Neighborhood disadvantage has consistently been associated with mental health and cognitive function, in addition to alterations in brain function and connectivity. However, positive environmental influences may buffer these effects. The aim of this study was to examine the association between neighborhood disadvantage and resting-state functional connectivity (rsFC), the moderating role of positive parenting and school environment, and relationships between disadvantage-associated rsFC patterns and mental health and cognition.

Methods
In this preregistered study, we tested this hypothesis in a large sample of 7618 children (aged 9–10 years) from the Adolescent Brain Cognitive Development (ABCD) study. Specifically, we analyzed the relationship between neighborhood disadvantage and system-level FC. We also tested whether positive family and school environmental factors and sex moderated effects. Finally, we investigated multivariate relationships between disadvantage-associated rsFC patterns and cognition and mental health.

Results
Disadvantage was associated with widespread alterations in FC across both higher-order (e.g., default mode network and dorsal attention network) and sensorimotor functional systems, some of which were moderated by positive environments. Implicated connections showed multivariate associations with behavior, whereby disadvantage-associated rsFC was generally associated with worse cognition and mental health. Disadvantage-associated connections also predicted variation in cognitive scores using machine learning models.

Conclusions
Our findings shed light on potential mechanisms (i.e., alteration of neural circuitry) through which neighborhood disadvantage may affect youth cognition and mental well-being. This work highlights the importance of positive family and school environments in mitigating some of these effects.

Cortical Thickness in bilingual and monolingual children: Relationships to language use and language skill

Vaughn KA, Nguyen MVH, Ronderos J, Hernandez AE. Cortical Thickness in bilingual and monolingual children: Relationships to language use and language skill. Neuroimage. 2021 Sep 7;243:118560. doi: 10.1016/j.neuroimage.2021.118560. Epub ahead of print. PMID: 34506917.

There is a growing body of evidence based on adult neuroimaging that suggests that the brain adapts to bilingual experiences to support language proficiency. The Adolescent Brain Cognitive Development (ABCD) Study is a useful source of data for evaluating this claim during childhood, as it involves data from a large sample of American children. Using the baseline ABCD Study data collected at ages nine and ten, the goal of this study was to identify differences in cortical thickness between bilinguals and monolinguals and to evaluate how variability in English vocabulary and English use within bilinguals might explain these group differences. We identified bilingual participants as children who spoke a non-English language and were exposed to the non-English language at home. We then identified a matched sample of English monolingual participants based on age, sex, pubertal status, parent education, household income, non-verbal IQ, and handedness. Bilinguals had thinner cortex than monolinguals in widespread cortical regions. Within bilinguals, more English use was associated with greater frontal and parietal cortical thickness; greater English vocabulary was associated with greater frontal and temporal cortical thickness. These findings replicate and extend previous research with bilingual children and highlight unexplained cortical thickness differences between bilinguals and monolinguals.

Children’s Knowledge of Cannabis and Other Substances in States with Different Cannabis Use Regulations

Ross JM, Rieselbach MM, Hewitt JK, Banich MT, Rhee SH. Children’s Knowledge of Cannabis and Other Substances in States with Different Cannabis Use Regulations. Subst Use Misuse. 2021 Sep 5:1-8. doi: 10.1080/10826084.2021.1972316. Epub ahead of print. PMID: 34486481.

Public acceptance of cannabis continues to increase across the US, yet there has been little research on how cannabis legalization affects young children. The present study compared knowledge of cannabis and other substances among children living in states with different cannabis laws and examined whether the association between such substance knowledge and externalizing behavior varies by state cannabis regulations. Methods: Participants were from the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®) at the baseline assessment (N = 11,875, ages 9-11, collected from 2016 to 2018). Chi-square difference tests were used to compare nested models testing group differences in knowledge of substances and the association between externalizing disorder/behavior and substance knowledge as a function of state legality of cannabis use (recreational, medical, low THC/CBD, none). Results: Children living in states with more permissive cannabis laws had a greater knowledge of cannabis and reported more alcohol experimentation. In contrast, knowledge regarding alcohol, tobacco, and other illicit drugs was not greater in children from states with more permissive cannabis laws. Externalizing disorder/behavior was not significantly associated with cannabis knowledge in any group and not significantly different across groups. The association between externalizing disorder/behavior and illicit drug knowledge was significant only in states with the recreational and medical use laws but did not differ significantly across groups. Conclusion: Children living in environments with more permissive cannabis regulations have greater knowledge of cannabis, but not other substances, and report more experimentation with alcohol.

Motivation and Cognitive Abilities as Mediators Between Polygenic Scores and Psychopathology in Children

Pat N, Riglin L, Anney R, Wang Y, Barch DM, Thapar A, Stringaris A. Motivation and Cognitive Abilities as Mediators Between Polygenic Scores and Psychopathology in Children. J Am Acad Child Adolesc Psychiatry. 2021 Sep 3:S0890-8567(21)01363-0. doi: 10.1016/j.jaac.2021.08.019. Epub ahead of print. PMID: 34506929.

Objective: Fundamental questions in biological psychiatry concern the mechanisms that mediate between genetic liability and psychiatric symptoms. Genetic liability for many common psychiatric disorders often confers transdiagnostic risk to develop a wide variety of psychopathological symptoms through yet unknown pathways. We examine the psychological and cognitive pathways that might mediate the relationship between genetic liability (indexed by polygenic scores; PS) and broad psychopathology (indexed by p factor and its underlying dimensions).

Method: We first identified which of the common psychiatric PSs (major depressive disorder [MDD], attention-deficit/hyperactivity disorder [ADHD], anxiety, bipolar, schizophrenia, autism) were associated with p factor. We then focused on three pathways: punishment sensitivity (reflected by behavioral inhibition system; BIS), reward sensitivity (reflected by behavioral activation system; BAS) and cognitive abilities (reflected by g factor based on 10 neurocognitive tasks). We applied structural equation modeling on the Adolescent Brain Cognitive Development (ABCD) dataset (n=4,814; 2,263 female children; 9-10 years old).

Results: MDD and ADHD PSs were associated with p factor. The association between MDD PS and psychopathology was partially mediated by punishment sensitivity and cognitive abilities: proportion mediated= 22.35%. Conversely, the influence of ADHD PS on psychopathology was partially mediated by reward sensitivity and cognitive abilities: proportion mediated=30.04%. The mediating role of punishment sensitivity was specific to the emotional/internalizing. This mediating role of both reward sensitivity and cognitive abilities was focusing on the behavioral/externalizing and neurodevelopmental dimensions of psychopathology.

Conclusion: We provide a better understanding of how genetic risks for MDD and ADHD confer risks for psychopathology and suggest potential prevention/intervention targets for children at-risk.

Morphology of the Prefrontal Cortex Predicts Body Composition in Early Adolescence: Cognitive Mediators and Environmental Moderators in the ABCD Study

Hall PA, Best J, Beaton EA, Sakib MN, Danckert J. Morphology of the Prefrontal Cortex Predicts Body Composition in Early Adolescence: Cognitive Mediators and Environmental Moderators in the ABCD Study. Soc Cogn Affect Neurosci. 2021 Sep 2:nsab104. doi: 10.1093/scan/nsab104. Epub ahead of print. PMID: 34471927.

Morphological features of the lateral prefrontal cortex (PFC) in late childhood and early adolescence may provide important clues as to the developmental etiology of clinical conditions such as obesity. Body composition measurements and structural brain imaging were performed on 11,226 youth at baseline (age 9 or 10) and follow-up (age 11 or 12). Baseline morphological features of the lateral PFC were examined as predictors of body composition. Findings revealed reliable associations between mid-frontal gyrus volume, thickness and surface area and multiple indices of body composition. These findings were consistent across both time points, and remained significant after covariate adjustment. Cortical thickness of the inferior frontal gyrus and lateral orbitofrontal cortex were also reliable predictors. Morphology effects on body composition were mediated by performance on a non-verbal reasoning task. Modest but reliable moderation effects were observed with respect to environmental self-regulatory demand after controlling for sex, race/ethnicity, income and methodological variables. Overall findings suggest that prefrontal cortex morphology is a reliable predictor of body composition in early adolescence, as mediated through select cognitive functions and partially moderated by environmental characteristics.

Sociodemographic Correlates of Contemporary Screen Time Use among 9-10-Year-Old Children

Nagata JM, Ganson KT, Iyer P, Chu J, Baker FC, Gabriel KP, Garber AK, Murray SB, Bibbins-Domingo K. Sociodemographic Correlates of Contemporary Screen Time Use among 9-10-Year-Old Children. J Pediatr. 2021 Sep 2:S0022-3476(21)00862-3. doi: 10.1016/j.jpeds.2021.08.077. Epub ahead of print. PMID: 34481807.

Objective: To determine sociodemographic correlates of contemporary screen time use among a diverse population-based sample of 9-10-year-old children.

Study design: In 2021, we analyzed cross-sectional baseline (2016-2018) data from the Adolescent Brain Cognitive Development (ABCD) Study (N=10,755). Multiple linear regression analyses were conducted to estimate associations between sociodemographic factors (sex, race/ethnicity, country of birth, household income, parental education) and six contemporary forms of screen time (television, videos [eg, YouTube], video games, social networking, texting, and video chat).

Results: On average, children reported 3.99 hours of screen time per day across six modalities, with the most time spent watching/streaming television shows/movies (1.31 hours), playing video games (1.06 hours), and watching/streaming videos (1.05 hours). On average, Black children reported 1.58 more hours of screen time per day and Asian children reported 0.35 less hours of screen time per day compared with White children (mean 3.46 hours per day), and these trends persisted across most modalities. Boys reported higher overall screen time (0.75 hours more) than girls, which was primarily attributed to video games and videos. Girls reported more time texting, social networking, and video chatting than boys. Higher income was associated with lower screen time usage across all modalities except video chat. However, in high-income households, Latinx children reported 0.65 more hours of screen time per day than White children.

Conclusions: Given the sociodemographic differences in child screen use, guideline implementation strategies can focus on key populations, encourage targeted counseling by pediatricians, and adapt Family Media Use Plans for diverse backgrounds.

The relationship between brain structure and general psychopathology in preadolescents

Mewton L, Lees B, Squeglia LM, Forbes MK, Sunderland M, Krueger R, Koch FC, Baillie A, Slade T, Hoy N, Teesson M. The relationship between brain structure and general psychopathology in preadolescents. J Child Psychol Psychiatry. 2021 Sep 1. doi: 10.1111/jcpp.13513. Epub ahead of print. PMID: 34468031.

Neural response to monetary loss among youth with disruptive behavior disorders and callous-unemotional traits in the ABCD study

Byrd AL, Hawes SW, Waller R, Delgado MR, Sutherland MT, Dick AS, Trucco EM, Riedel MC, Pacheco-Colón I, Laird AR, Gonzalez R. Neural response to monetary loss among youth with disruptive behavior disorders and callous-unemotional traits in the ABCD study. Neuroimage Clin. 2021 Sep 1;32:102810. doi: 10.1016/j.nicl.2021.102810. Epub ahead of print. PMID: 34530359.

Etiological models highlight reduced punishment sensitivity as a core risk factor for disruptive behavior disorders (DBD) and callous-unemotional (CU) traits. The current study examined neural sensitivity to the anticipation and receipt of loss, one key aspect of punishment sensitivity, among youth with DBD, comparing those with and without CU traits. Data were obtained from the Adolescent Brain and Cognitive Development (ABCD)SM Study (N = 11,874; Mage = 9.51; 48% female). Loss-related fMRI activity during the monetary incentive delay task was examined across 16 empirically-derived a priori brain regions (e.g., striatum, amygdala, insula, anterior cingulate cortex, medial prefrontal cortex) and compared across the following groups: (1) typically developing (n = 693); (2) DBD (n = 995), subdivided into those (3) with CU traits (DBD + CU, n = 198), and (4) without CU traits (DBD-only, n = 276). Latent variable modeling was also employed to examine network-level activity. There were no significant between-group differences in brain activity to loss anticipation or receipt. Null findings were confirmed with and without covariates, using alternative grouping approaches, and in dimensional models. Network-level analyses also demonstrated comparable activity across groups during loss anticipation and receipt. Findings suggest that differences in punishment sensitivity among youth with DBD are unrelated to loss anticipation or receipt. More precise characterizations of other aspects punishment sensitivity are needed to understand risk for DBD and CU traits.

Similar but distinct – Effects of different socioeconomic indicators on resting state functional connectivity: findings from the Adolescent Brain Cognitive Development (ABCD) Study®

Rakesh D, Zalesky A, Sarah Whittle S (2021). Similar but distinct – Effects of different socioeconomic indicators on resting state functional connectivity: findings from the Adolescent Brain Cognitive Development (ABCD) Study®. Developmental Cognitive Neuroscience, Volume 51, October 2021, 101005, ISSN 1878-9293, https://doi.org/10.1016/j.dcn.2021.101005.

Early socioeconomic status (SES) has consistently been associated with child health and cognitive outcomes, in addition to alterations in brain function and connectivity. The goal of the present study was to probe the effects of different facets of SES (parent education, income, and neighborhood disadvantage), that likely represent varying aspects of the environment, on resting state functional connectivity (rsFC). We investigated this question in a large sample of 9475 children (aged 9-10 years) from the Adolescent Brain Cognitive Development (ABCD) Study. Specifically, we analyzed the association between household SES (parent education, income-to-needs ratio) and neighborhood disadvantage, and system-level rsFC using within-sample split-half replication. We then tested whether the associations were unique to each SES measure, and whether household SES and neighborhood disadvantage had interactive effects on rsFC. SES measures had both common and distinct effects on rsFC, with sensory-motor systems (e.g., sensorimotor network) and cognitive networks (e.g., front-parietal network) particularly implicated. The association between neighborhood disadvantage and sensorimotor network connectivity was less pronounced in the presence of high income-to-needs. Findings demonstrate that different facets of SES have distinct and interacting effects on rsFC, highlighting the importance of considering different indicators when studying the effects of SES on the brain.

Reducing the effects of motion artifacts in fMRI: A structured matrix completion approach

Balachandrasekaran A, Cohen AL, Afacan O, Warfield SK, Gholipour A. Reducing the effects of motion artifacts in fMRI: A structured matrix completion approach. IEEE Trans Med Imaging. 2021 Aug 25;PP. doi: 10.1109/TMI.2021.3107829. Epub ahead of print. PMID: 34432631.

Functional MRI (fMRI) is widely used to study the functional organization of normal and pathological brains. However, the fMRI signal may be contaminated by subject motion artifacts that are only partially mitigated by motion correction strategies. These artifacts lead to distance-dependent biases in the inferred signal correlations. To mitigate these spurious effects, motion-corrupted volumes are censored from fMRI time series. Censoring can result in discontinuities in the fMRI signal, which may lead to substantial alterations in functional connectivity analysis. We propose a new approach to recover the missing entries from censoring based on structured low rank matrix completion. We formulated the artifact-reduction problem as the recovery of a super-resolved matrix from unprocessed fMRI measurements. We enforced a low rank prior on a large structured matrix, formed from the samples of the time series, to recover the missing entries. The recovered time series, in addition to being motion compensated, are also slice-time corrected at a fine temporal resolution. To achieve a fast and memory-efficient solution for our proposed optimization problem, we employed a variable splitting strategy. We validated the algorithm with simulations, data acquired under different motion conditions, and datasets from the ABCD study. Functional connectivity analysis showed that the proposed reconstruction resulted in connectivity matrices with lower errors in pair-wise correlation than non-censored and censored time series based on a standard processing pipeline. In addition, seed-based correlation analyses showed improved delineation of the default mode network. These demonstrate that the method can effectively reduce the adverse effects of motion in fMRI analysis.

Early Adolescent Substance Use Before and During the COVID-19 Pandemic: A Longitudinal Survey in the ABCD Study Cohort

Pelham III WE, Tapert S, Robledo Gonzalez M, McCabe CJ, Lisdahl KM, Alzueta E, Baker FC, Breslin FJ, Dick AS, Dowling GJ, Guillaume M, Hoffman EA, Marshall AT, McCandliss BD, Sheth CS, Sowell ER, Thompson WK, Van Rinsveld AM, Wade NE, Brown SA. Early Adolescent Substance Use Before and During the COVID-19 Pandemic: A Longitudinal Survey in the ABCD Study Cohort. Journal of Adolescent Health, Volume 69, Issue 3, P390-397, September 01, 2021. DOI:https://doi.org/10.1016/j.jadohealth.2021.06.015.

Purpose
Evaluate changes in early adolescent substance use during the coronavirus disease 2019 (COVID-19) pandemic using a prospective, longitudinal, nationwide cohort.

Methods
Participants were enrolled in the Adolescent Brain Cognitive Development Study. A total of 7,842 youth (mean age = 12.4 years, range = 10.5–14.6) at 21 study sites across the U.S. completed a three-wave assessment of substance use between May and August 2020. Youth reported whether they had used alcohol, nicotine, cannabis, or other substances in the past 30 days. Data were linked to prepandemic surveys that the same youth had completed in the years 2018–2020, before the advent of the COVID-19 pandemic.

Results
Past-30-day substance use remained stable in the 6 months since stay-at-home orders were first issued in U.S. states/counties; was primarily episodic (1–2 days in the past month); and was typically limited to a single substance. Using pretest/posttest and age-period designs, we found that compared to before the pandemic, fewer youth were using alcohol and more youth were using nicotine or misusing prescription drugs. During the pandemic, youth were more likely to use substances when they were more stressed by pandemic-related uncertainty; their family experienced material hardship; their parents used alcohol or drugs; or they experienced greater depression or anxiety. Neither engagement in social distancing nor worry about COVID-19 infection was associated with substance use. Several risk factors were stronger among older (vs. younger) adolescents.

Conclusions
Among youth in early adolescence, advent of the COVID-19 pandemic was associated with decreased use of alcohol and increased use of nicotine and misuse of prescription drugs.

Association Between Discrimination Stress and Suicidality in Preadolescent Children

Argabright ST, Visoki E, Moore TM, Ryan DT, DiDomenico GE, Njoroge WFM, Taylor JH, Guloksuz S, Gur RC, Gur RE, Benton TD, Barzilay R. Association Between Discrimination Stress and Suicidality in Preadolescent Children. J Am Acad Child Adolesc Psychiatry. 2021 Aug 20:S0890-8567(21)01355-1. doi: 10.1016/j.jaac.2021.08.011. Epub ahead of print. PMID: 34425231.

Objective: US youth suicide rates are increasing in recent years, especially in Black Americans, the reasons for which are unclear. Environmental adversity is key in youth suicidality, hence there is a need to study stressors that disproportionately impact Black youths. We aimed to disentangle the unique contribution of racial/ethnic discrimination from other adversities associated with childhood suicidal ideation and attempts (suicidality).

Method: We analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study® that included a large, diverse sample of US children (N=11,235, mean age 10.9 years, 20.2% Black) assessed for multiple environmental adversities including discrimination. Multivariate regression models tested the association of self-reported racial/ethnic discrimination with suicidality, covarying for multiple confounders including other discrimination types (towards non-US-born individuals; sexual orientation-based; weight-based). Matched analyses contrasted effects of racial/ethnic discrimination and racial identity on suicidality.

Results: Black youths reported more discrimination and higher suicidality rates than non-Black youths. High racial/ethnic discrimination was positively and significantly associated with suicidality, adjusting for other discrimination types (odds ratio [OR]=2.6, 95%CI=2.1-3.2). Findings remained significant after adjusting for multiple suicidality risk factors. Once experienced, racial/ethnic discrimination was similarly associated with suicidality in White, Black, and Hispanic youths. Matched analyses revealed that racial/ethnic discrimination was associated with suicidality (relative risk [RR]=2.7, 95%CI=2-3.5), while Black race was not (RR=0.9, 95%CI=0.7-1.2).

Conclusion: Racial/ethnic discrimination is disproportionately experienced by Black children, and is associated with preadolescent suicidality, over and above other adversities. Findings highlight the need to address discrimination as part of suicide prevention strategies. Cross-sectional design hampers causal inferences.

Shared Genetic Etiology between Cortical Brain Morphology and Tobacco, Alcohol, and Cannabis Use

Rabinowitz JA, Campos AI, Ong JS, García-Marín LM, Alcauter S, Mitchell BL, Grasby KL, Cuéllar-Partida G, Gillespie NA, Huhn AS, Martin NG, Thompson PM, Medland SE, Maher BS, Rentería ME. Shared Genetic Etiology between Cortical Brain Morphology and Tobacco, Alcohol, and Cannabis Use. Cereb Cortex. 2021 Aug 11:bhab243. doi: 10.1093/cercor/bhab243. Epub ahead of print. PMID: 34379727.

Genome-wide association studies (GWAS) have identified genetic variants associated with brain morphology and substance use behaviors (SUB). However, the genetic overlap between brain structure and SUB has not been well characterized. We leveraged GWAS summary data of 71 brain imaging measures and alcohol, tobacco, and cannabis use to investigate their genetic overlap using linkage disequilibrium score regression. We used genomic structural equation modeling to model a “common SUB genetic factor” and investigated its genetic overlap with brain structure. Furthermore, we estimated SUB polygenic risk scores (PRS) and examined whether they predicted brain imaging traits using the Adolescent Behavior and Cognitive Development (ABCD) study. We identified 8 significant negative genetic correlations, including between (1) alcoholic drinks per week and average cortical thickness, and (2) intracranial volume with age of smoking initiation. We observed 5 positive genetic correlations, including those between (1) insula surface area and lifetime cannabis use, and (2) the common SUB genetic factor and pericalcarine surface area. SUB PRS were associated with brain structure variation in ABCD. Our findings highlight a shared genetic etiology between cortical brain morphology and SUB and suggest that genetic variants associated with SUB may be causally related to brain structure differences.

Predicting fluid intelligence in adolescence from structural MRI with deep learning methods

Susmita Saha, Alex Pagnozzi, Dana Bradford, Jurgen Fripp, Predicting fluid intelligence in adolescence from structural MRI with deep learning methods, Intelligence, Volume 88, Sept-Oct 2021, 101568, ISSN 0160-2896, https://doi.org/10.1016/j.intell.2021.101568.

Background
The objective of this study was to investigate the potential of unsegmented structural T1w MR images of adolescent brain for predicting uncorrected/actual fluid intelligence scores without any predefined feature extraction. We also examined whether prediction of uncorrected scores is simply a harder problem from both biological and technical point of view, than prediction of residualised scores.

Methods

ABCD (Adolescent Brain Cognitive Development) study data was used from 7709 children aged 9–10, including T1-weighted MRIs and fluid intelligence scores, with data split into training (n = 3739), validation (n = 415) and test (n = 3555) subsets. We developed several deep learning convolutional neural network (CNN) models for both actual and residualised fluid intelligence score prediction from the MR images. State of the art, conventional or reverse 2D/3D CNN architectures were developed to perform the regression task and optimised based on Pearson’s correlation coefficient, r. The models were then compared with published results on the same dataset.

Results

Our proposed model achieved prediction accuracies of r = 0.18 (p < 0.001) for the validation and r = 0.1 (p < 0.05) for the test, for actual IQ prediction. Our results showed that, although we achieved ~10 times higher correlation for the residualised score prediction than the correlations reported by previous CNN studies, using the same unsegmented MR images, it could not exceed the actual IQ prediction performance. This suggests that the image features associated with covariates aided up in the uncorrected score prediction rather than making the task harder.

Conclusion

Our deep learning CNN was able to establish a weak but stable correlation between structural brain features and raw fluid intelligence. To improve neuroimaging-based fluid intelligence prediction performance, future studies will be required to explore ensembled regression strategies with multiple machine learning algorithms on multimodal MRIs.

Relationships between apparent cortical thickness and working memory across the lifespan – effects of genetics and socioeconomic status

Stine K. Krogsrud, Athanasia M. Mowinckel, Donatas Sederevicius, Didac Vidal-Piñeiro, Inge K. Amlien, Yunpeng Wang, Øystein Sørensen, Kristine B. Walhovd, Anders M. Fjell (2021). Relationships between apparent cortical thickness and working memory across the lifespan – effects of genetics and socioeconomic status, Developmental Cognitive Neuroscience, Volume 51, October 2021, 100997, ISSN 1878-9293, https://doi.org/10.1016/j.dcn.2021.100997.

Working memory (WM) supports several higher-level cognitive abilities, yet we know less about factors associated with development and decline in WM compared to other cognitive processes. Here, we investigated lifespan changes in WM capacity and their structural brain correlates, using a longitudinal sample including 2358 magnetic resonance imaging (MRI) scans and WM scores from 1656 participants (4.4-86.4 years, mean follow-up interval 4.3 years). 8764 participants (9.0-10.9 years) with MRI, WM scores and genetic information from the Adolescent Brain Cognitive Development study were used for follow-up analyses. Results showed that both the information manipulation component and the storage component of WM improved during childhood and adolescence, but the age-decline could be fully explained by reductions in passive storage capacity alone. Greater WM function in development was related to apparent thinner cortex in both samples, also when general cognitive function was accounted for. The same WM-apparent thickness relationship was found for young adults. The WM-thickness relationships could not be explained by SNP-based co-heritability or by socioeconomic status. A larger sample with genetic information may be necessary to disentangle the true gene-environment effects. In conclusion, WM capacity changes greatly through life and has anatomically extended rather than function-specific structural cortical correlates.

Racial Disparities in Elementary School Disciplinary Actions: Findings From the ABCD Study

Fadus MC, Valadez EA, Bryant BE, Garcia AM, Neelon B, Tomko RL, Squeglia LM. Racial Disparities in Elementary School Disciplinary Actions: Findings From the ABCD Study. Journal of the American Academy of Child & Adolescent Psychiatry, Vol 60, Issue 8, P998-1009, AUGUST 01, 2021.

Objective
Detentions and suspensions are common practices of school discipline, despite evidence that they are largely ineffective and disproportionately affect children from racial and ethnic minority backgrounds, particularly Black children, and children of lower socioeconomic status. However, few studies have examined suspension and detention rates among race, ethnicity, and family structure (single parent versus secondary caregiver) when controlling for typical behaviors associated with detention and suspension such as externalizing symptoms, age, sex, family income, family education, family conflict, and special education needs.

Method
Caregivers of 11,875 children between ages 9 and 10 years from the Adolescent Brain Cognitive Development (ABCD) study completed a questionnaire assessing their child’s demographics, family information, emotions and behaviors, and past-year school discipline history. Data were analyzed with logistic regression, implemented with a generalized estimating equations model.

Results
5.4% of children received a detention or suspension. Controlling for typical predictors of behaviors, Black and multiracial Black children had up to 3.5 times greater odds of receiving a detention or suspension than White children; there were no disciplinary differences for Hispanic or Asian children compared to White children. Children from single-parent households had 1.4 times the odds of receiving detentions or suspensions than children in homes with a secondary caregiver.

Conclusion
Disciplinary actions that can impair typical childhood development, lead to academic failure and dropout, and cause significant emotional and psychological distress disproportionately affect Black children, multiracial Black children, and children from single-parent homes. Racism in elementary school discipline can perpetuate disparities in today’s educational system.

 

Substance use patterns in 9-10 year olds: Baseline findings from the adolescent brain cognitive development (ABCD) study

Krista M. Lisdahl, Susan Tapert, Kenneth J. Sher, Raul Gonzalez, Sara Jo Nixon, Sarah W. Feldstein Ewing, Kevin P. Conway, Alex Wallace, Ryan Sullivan, Kelah Hatcher, Christine Kaiver, Wes Thompson, Chase Reuter, Hauke Bartsch, Natasha E. Wade, Joanna Jacobus, M.D. Albaugh, N. Allgaier, A.P. Anokhin, K. Bagot, F.C. Baker, M.T. Banich, D.M. Barch, A. Baskin-Sommers, F.J. Breslin, S.A. Brown, V. Calhoun, B.J. Casey, B. Chaarani, L. Chang, D.B. Clark, C. Cloak, R.T. Constable, L.B. Cottler, R. Dagher, M. Dapretto, A. Dick, E.K. Do, N.U.F. Dosenbach, G.J. Dowling, D.A. Fair, P. Florsheim, J.J. Foxe, E.G. Freedman, N. Friedman, H.P. Garavan, D.G. Gee, M.D. Glantz, P. Glaser, M.R. Gonzalez, K.M. Gray, S. Grant, F. Haist, S. Hawes, S.G. Heeringa, R. Hermosillo, M.M. Herting, J.M. Hettema, J.K. Hewitt, C. Heyser, E.A. Hoffman, K.D. Howlett, R.S. Huber, M.A. Huestis, L.W. Hyde, W.G. Iacono, A. Isaiah, M.Y. Ivanova, R.S. James, T.L. Jernigan, N.R. Karcher, J.M. Kuperman, A.R. Laird, C.L. Larson, K.H. LeBlanc, M.F. Lopez, M. Luciana, B. Luna, H.H. Maes, A.T. Marshall, M.J. Mason, E. McGlade, A.S. Morris, C. Mulford, B.J. Nagel, G. Neigh, C.E. Palmer, M.P. Paulus, D. Pecheva, D. Prouty, A. Potter, L.I. Puttler, N. Rajapakse, J.M Ross, M. Sanchez, C. Schirda, J. Schulenberg, C. Sheth, P.D. Shilling, E.R. Sowell, N. Speer, L. Squeglia, C. Sripada, J. Steinberg, M.T. Sutherland, R. Tomko, K. Uban, S. Vrieze, S.R.B. Weiss, D. Wing, D.A. Yurgelun-Todd, R.A. Zucker, Mary M. Heitzeg (2021). Substance use patterns in 9-10 year olds: Baseline findings from the adolescent brain cognitive development (ABCD) study, Drug and Alcohol Dependence, Volume 227, 1 October 2021, 108946, ISSN 0376-8716, https://doi.org/10.1016/j.drugalcdep.2021.108946.

Background
The Adolescent Brain Cognitive Development ™ Study (ABCD StudyⓇ) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12.

Methods
This study aims to report the detailed ABCD StudyⓇ SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort’s early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD).

Primary Results
At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, 0.1 % used cannabis, <0.02 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p’s<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03).

Conclusions
ABCD Study participants aged 9–10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort.

Testing whether implicit emotion regulation mediates the association between discrimination and symptoms of psychopathology in late childhood: An RDoC perspective

Vargas TG, Mittal VA. Testing whether implicit emotion regulation mediates the association between discrimination and symptoms of psychopathology in late childhood: An RDoC perspective. Dev Psychopathol. 2021 Jul 29:1-14. doi: 10.1017/S0954579421000638. Epub ahead of print. PMID: 34323206.

Discrimination has been associated with adverse mental health outcomes, though it is unclear how early in life this association becomes apparent. Implicit emotion regulation, developing during childhood, is a foundational skill tied to a range of outcomes. Implicit emotion regulation has yet to be tested as an associated process for mental illness symptoms that can often emerge during this sensitive developmental period. Youth aged 9-11 were recruited for the Adolescent Brain Cognitive Development (ABCD) study. Associations between psychotic-like experiences, depressive symptoms, and total discrimination (due to race, ethnicity, nationality, weight, or sexual minority status) were tested, as well as associations with implicit emotion regulation measures (emotional updating working memory and inhibitory control). Analyses examined whether associations with symptoms were mediated by implicit emotion regulation. Discrimination related to decreased implicit emotion regulation performance, and increased endorsement of depressive symptoms and psychotic-like experiences. Emotional updating working memory performance partially mediated the association between discrimination and psychotic-like experiences, while emotional inhibitory control did not. Discrimination and implicit emotion regulation could serve as putative transdiagnostic markers of vulnerability. Results support the utility of using multiple units of analysis to improve understanding of complex emerging neurocognitive functions and developmentally sensitive periods.

Prenatal caffeine exposure: association with neurodevelopmental outcomes in 9- to 11-year-old children

Zhang R, Manza P, Volkow ND. Prenatal caffeine exposure: association with neurodevelopmental outcomes in 9- to 11-year-old children. J Child Psychol Psychiatry. 2021 Jul 27. doi: 10.1111/jcpp.13495. Epub ahead of print. PMID: 34318489.

Background: Despite the widespread use of caffeine including consumption during pregnancy, the effect of prenatal caffeine exposure on child brain development and behavior is unclear.

Methods: To address this, we used data from the Adolescent Brain and Cognitive Development Study (n = 11,875 children aged 9-11 years from 22 sites across the United States). We explored the associations between prenatal caffeine exposure and various developmental outcomes including birth outcomes, physical health, behavior problems, cognition, substance use and brain structure in children, and evaluated dose effects.

Results: Among 9,978 children (4,745 females) who had valid data for prenatal caffeine exposure and whose mothers did not use drugs of abuse after knowing of pregnancy, 4,170 (41.79%) had no prenatal caffeine exposure, 2,292 (22.97%) had daily, 1,933 (19.37%) had weekly, and 1,583 (15.86%) had less than weekly exposures. Prenatal caffeine exposure including the widely recommended ‘safe’ dose was associated with greater externalizing problems, whereas greater BMI and soda consumption were only observed in children with high dose exposures (3+ per day). Notably, the effect size for association of externalizing problems with prenatal caffeine exposure was comparable with that reported for prenatal alcohol (The American Journal of Psychiatry, 177, 2020 and 1060) and prenatal cannabis (JAMA Psychiatry, 78, 2020 and 64) exposures from previous ABCD publications. Additionally, prenatal caffeine exposure was associated with brain structural changes that included greater posterior and lower frontal cortical thickness and altered parietooccipital sulcal depth.

Conclusions: The recommended ‘safe’ dose of caffeine during pregnancy should be carefully studied to assess whether the behavioral and brain correlates observed here are clinically relevant and determine whether it needs adjustment. Because of the high prevalence of caffeine use in the general population, studies on prenatal exposure to drugs of abuse should include prenatal caffeine use as a covariate.

Is executive dysfunction a risk marker or consequence of psychopathology? A test of executive function as a prospective predictor and outcome of general psychopathology in the adolescent brain cognitive development study®

Romer AL, Pizzagalli DA. Is executive dysfunction a risk marker or consequence of psychopathology? A test of executive function as a prospective predictor and outcome of general psychopathology in the adolescent brain cognitive development study®. Dev Cogn Neurosci. 2021 Jul 22;51:100994. doi: 10.1016/j.dcn.2021.100994. Epub ahead of print. PMID: 34332330.

A general psychopathology (‘p’) factor captures shared variation across mental disorders. One hypothesis is that poor executive function (EF) contributes to p. Although EF is related to p concurrently, it is unclear whether EF predicts or is a consequence of p. For the first time, we examined prospective relations between EF and p in 9845 preadolescents (aged 9-12) from the Adolescent Brain Cognitive Development Study® longitudinally over two years. We identified higher-order factor models of psychopathology at baseline and one- and two-year follow-up waves. Consistent with previous research, a cross-sectional inverse relationship between EF and p emerged. Using residualized-change models, baseline EF prospectively predicted p factor scores two years later, controlling for prior p, sex, age, race/ethnicity, parental education, and family income. Baseline p factor scores also prospectively predicted change in EF two years later. Tests of specificity revealed that bi-directional prospective relations between EF and p were largely generalizable across externalizing, internalizing, neurodevelopmental, somatization, and detachment symptoms. EF consistently predicted change in externalizing and neurodevelopmental symptoms. These novel results suggest that executive dysfunction is both a risk marker and consequence of general psychopathology. EF may be a promising transdiagnostic intervention target to prevent the onset and maintenance of psychopathology.

Genetic and environmental influences on executive functions and intelligence in middle childhood

Freis SM, Morrison CL, Lessem JM, Hewitt JK, Friedman NP (2021). Genetic and environmental influences on executive functions and intelligence in middle childhood. Dev Sci. 2021 Jul 20. doi: 10.1111/desc.13150. Epub ahead of print. PMID: 34288270.

Executive functions (EFs) and intelligence (IQ) are phenotypically correlated. In twin studies, latent variables for EFs and IQ display moderate to high heritability estimates; however, they show variable genetic correlations in twin studies spanning childhood to middle age. We analyzed data from over 11,000 children (9-10-year-olds, including 749 twin pairs) in the Adolescent Brain Cognitive Development (ABCD) Study to examine the phenotypic and genetic relations between EFs and IQ in childhood. We identified two EF factors — Common EF and Updating-Specific — which were both related to IQ (rs = .64-.81). Common EF and IQ were heritable (53-67%), and their genetic correlation (rG = .86) was not significantly different than 1. These results suggest that EFs and IQ are phenotypically but not genetically separable in middle childhood, meaning that this phenotypic separability may be influenced by environmental factors. This article is protected by copyright. All rights reserved.

Heterogeneity Within Youth With Childhood-Onset Conduct Disorder in the ABCD Study

Brislin SJ, Martz ME, Cope LM, Hardee JE, Weigard A, Heitzeg MM. Heterogeneity Within Youth With Childhood-Onset Conduct Disorder in the ABCD Study. Front Psychiatry. 2021 Jul 16;12:701199. doi: 10.3389/fpsyt.2021.701199. PMID: 34335337; PMCID: PMC8322519.

The purpose of this study was to examine if personality traits can be used to characterize subgroups of youth diagnosed with childhood-onset conduct disorder (CD). Participants were 11,552 youth from the Adolescent Brain Cognitive Development study. Data used in this report came from doi: 10.15154/1504041 (M age 9.92; 45.3% female, 49.6% white, 19.0% Hispanic). A subset of this sample (n = 365) met criteria for CD. Latent profile analyses (LPA) were performed on this subgroup (n = 365) to define profiles of individuals with CD based on self-report measures of impulsivity, punishment sensitivity, reward response, and callous-unemotional traits. Follow up analyses determined if these groups differed on clinically relevant variables including psychopathology, environmental risk factors, social risk factors, and neurocognitive functioning. Participants with a CD diagnosis scored significantly higher on psychological, environmental, social, and neurocognitive risk factors. The LPA revealed three unique profiles, which differed significantly on liability for broad psychopathology and domain-specific liability for externalizing psychopathology but were largely matched on environmental and social risk factors. These unique configurations provide a useful way to further parse clinically relevant subgroups within youth who meet criteria for childhood-onset CD, setting the stage for prospective longitudinal research using these latent profiles to better understand the development of youth with childhood-onset CD.

Psychotic-like experiences and polygenic liability in the ABCD Study®

Karcher NR, Paul SE, Johnson EC, Hatoum AS, Baranger DA, Agrawal A, Thompson WK, Barch DM, Bogdan R (2021). Psychotic-like experiences and polygenic liability in the ABCD Study®. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Jul 13:S2451-9022(21)00191-9. doi: 10.1016/j.bpsc.2021.06.012. Epub ahead of print. PMID: 34271214.

Background: Childhood psychotic-like experiences (PLEs) often precede the development of later severe psychopathology. The current study examined whether childhood PLEs are associated with several psychopathology-related polygenic scores (PGS), and additionally examined possible neural and behavioral mechanisms.

Methods: Adolescent Brain Cognitive Development℠ Study baseline data from children with European ancestry (n=4,650; ages 9-10; 46.8% female) were used to estimate associations between PLEs (i.e., both total and presence of significantly distressing) and PGS for psychopathology (i.e., schizophrenia, psychiatric cross-disorder risk, PLEs) and related phenotypes (i.e., educational attainment [EDU]), birth-weight, inflammation). We also assessed whether variability in brain structure indices (i.e., volume, cortical thickness, surface area), as well as behaviors proximal to PGS (e.g., cognition for EDU), indirectly linked PGS to PLEs using mediational models.

Results: Total and significantly distressing PLEs were associated with EDU and cross-disorder PGS (all %ΔR2s=0.202-0.660%; pFDRs<0.006). Significantly distressing PLEs were also associated with higher schizophrenia and PLEs PGS (both %ΔR2=0.120-0.171%; pFDRs<0.03). There was evidence global brain volume metrics and cognitive performance indirectly linked EDU PGS to PLEs (estimated proportion mediated: 3.33-32.22%).

Conclusions: Total and significantly distressing PLEs were associated with genomic risk indices of broad-spectrum psychopathology risk (i.e., EDU and cross-disorder PGS). Significantly distressing PLEs were also associated with genomic risk for psychosis (i.e., schizophrenia, PLEs). Global brain volume metrics and PGS-proximal behaviors represent promising putative intermediary phenotypes that may indirectly link genomic risk to psychopathology. Broadly, polygenic scores derived from genome-wide association studies of adult samples generalize to indices of psychopathology risk among children.

History of depression, elevated BMI, and waist-to-height ratio in pre-adolescent children

Lewis-de Los Angeles WW, Liu RT (2021). History of depression, elevated BMI, and waist-to-height ratio in pre-adolescent children. Psychosom Med. 2021 Jul 13. doi: 10.1097/PSY.0000000000000982. Epub ahead of print. PMID: 34267084.

Objective: To evaluate whether a history of depression or self-injurious thoughts and behaviors predict elevated BMI and elevated waist-to-height ratio in pre-adolescents.

Methods: Baseline data were evaluated from a large, nationally representative cohort study of 9- and 10-year-old children (unweighted n = 11,875), the Adolescent Brain and Cognitive Development (ABCD) study.

Results: In the weighted sample, 10.6 % of children had a history of depression, 7.0% had engaged in non-suicidal self-injury, 13.1% had experienced suicidal ideation in their lifetime, and 1.1% had a history of attempted suicide. 34.1% of children had an elevated BMI in the overweight or obese range and 31.9% of children had a waist-to-height ratio > 0.5. In multivariate analyses, history of depression was associated with elevated BMI and waist-to-height ratio. Furthermore, interactions with sex were found; girls with a history of depression were more likely to have an elevated BMI (OR 1.47, 95% CI: 1.24-1.74) and elevated waist-to-height ratio (OR 1.48, 95% CI: 1.18-1.86) than girls without a history of depression, but no differences were observed between boys with and without a history of depression. Self-injurious thoughts and behaviors were not associated with elevated BMI or elevated waist-to-height.

Conclusions: In this study, nine- and ten-year-old girls with a history of depression were more likely to have an elevated BMI and elevated waist-to-height ratio than girls with no history of depression. These results provide important clinical context in caring for pre-adolescents with a history of depression.

Parental Education and Children’s Sleep Disturbance: Minorities’ Diminished Returns

Assari S (2021). Parental Education and Children’s Sleep Disturbance: Minorities’ Diminished Returns. Int J Epidemiol Res. 2021 Winter;8(1):31-39. PMID: 34263059; PMCID: PMC8277116.

Background and aims: While increased parental education reduces children’s sleep problems, less is known about racial variation in such protection. According to Minorities’ Diminished Returns (MDRs) theory, economic resources such as parental education show weaker health effects for minority groups such as Blacks and Latinos than non-Latino Whites, which is due to racism and social stratification. In this study, we investigated the association between parental education and children’s sleep problems, as a proxy of sleep problems, by race.

Methods: This cross-sectional study included 11718 American children aged 9-10. All participants were recruited to the Adolescent Brain Cognitive Development (ABCD) study. The independent variable was parental education, a five-level nominal variable. The dependent variable – sleep problems, was a continuous variable. Race/ethnicity was the effect modifier. Age, sex, and marital status were the covariates. Mixed-effects regression models were used for data analysis.

Results: Parental education was associated with children’s sleep problems. However, there was a weaker inverse association seen in non-Latino Black and Latino families compared to non-Latino White families. This was documented by a significant statistical interaction between race and ethnicity and parental education on children’s sleep problems.

Conclusion: Diminished protective effect of parental education on children’s sleep problems for non- Latino Black and Latino families compared to non-Latino White families is similar to the MDRs in other domains. Worse than expected sleep may contribute to higher-than-expected health risks of middle-class Black and Latino children.

Imaging and health metrics in incidental cerebellar tonsillar ectopia: findings from the Adolescent Brain Cognitive Development Study (ABCD)

Nwotchouang BST, Ibrahimy A, Loth DM, Labuda E, Labuda N, Eppleheimer M, Labuda R, Bapuraj JR, Allen PA, Klinge P, Loth F. Imaging and health metrics in incidental cerebellar tonsillar ectopia: findings from the Adolescent Brain Cognitive Development Study (ABCD). Neuroradiology. 2021 Jul 11. doi: 10.1007/s00234-021-02759-y. Epub ahead of print. PMID: 34247260.

Purpose: Incidental cerebellar tonsillar ectopia (ICTE) that meets the radiographic criterion for Chiari malformation type I (CMI) is an increasingly common finding in the clinical setting, but its significance is unclear. The present study examined posterior cranial fossa (PCF) morphometrics and a broad range of health instruments of pediatric ICTE cases and matched controls extracted from the Adolescent Brain Cognitive Development (ABCD) dataset.

Methods: One-hundred-six subjects with ICTE and 106 matched controls without ICTE were identified from 11,411 anatomical MRI of healthy screened pediatric subjects from the ABCD project. Subjects were matched by sex, age, body mass index, race, and ethnicity. Twenty-two brain morphometrics and 22 health instruments were compared between the two groups to identify unrecognized CMI symptoms and assess the general health impact of ICTE.

Results: Twelve and 15 measures were significantly different between the ICTE and control groups for females and males, respectively. Notably, for females, the anterior CSF space was significantly smaller (p = 0.00005) for the ICTE group than controls. For males, the clivus bone length was significantly shorter (p = 0.0002) for the ICTE group compared to controls. No significant differences were found among the 22 health instruments between the two groups.

Conclusion: This study demonstrated that pediatric ICTE subjects have similar PCF morphometrics to adult CMI. ICTE alone did not appear to cause any unrecognized CMI symptoms and had no impact on the subjects’ current mental, physical, or behavioral health. Still, given their cranial and brain morphology, these cases may be at risk for adult-onset symptomatic CMI.

Child reward neurocircuitry and parental substance use history: Findings from the adolescent brain cognitive development study

Kwarteng AE, Rahman MM, Gee DG, Infante MA, Tapert SF, Curtis BL (2021). Child reward neurocircuitry and parental substance use history: Findings from the adolescent brain cognitive development study, Addictive Behaviors, Volume 122, 2021, 107034, ISSN 0306-4603, https://doi.org/10.1016/j.addbeh.2021.107034.

Background
Substance use research has focused on family history of alcohol use disorders but less on other addictions in biological family members. We examined how parental substance use history relates to reward system functioning, specifically nucleus accumbens (NAcc) and putamen activation at age 9-10 in the Adolescent Brain Cognitive Development (ABCD) Study. This research hopes to address limitations in prior literature by focusing analyses on a large, substance-naïve sample.

Method
We included ABCD participants with valid Monetary Incentive Delay task fMRI Baseline data and parent substance use history at project baseline from Data Release 2.0 (N =10,622). Parent-history-positive (PH+) participants had one or both biological parents with a history of two+ problems with alcohol (n = 741; PH+A) and/or other drugs (n =638; Ph+D). Of participants who were parent-history-negative (PH-) for alcohol and/or drugs, a stratified random sample based on six sociodemographic variables was created and matched to the PH+ group (PH-A n = 699; PH-D n = 615). The contrast of interest was anticipation of a large reward vs. neutral response.

Results
PH+A youth had more activation in the right NAcc during large reward anticipation than PH-A. PH+D youth showed enhanced left putamen activation during large reward anticipation than PH-D youth. Bayesian hypothesis testing showed moderate evidence (BF > 3) in favor of the null hypothesis.

Conclusion
These findings suggest that pre-adolescents whose biological parents had a history of substance-related problems show small differences in reward processing compared to their PH- peers.

Psychiatric comorbidity of eating disorders in children between the ages of 9 and 10

Convertino AD, Blashill AJ. Psychiatric comorbidity of eating disorders in children between the ages of 9 and 10. J Child Psychol Psychiatry. 2021 Jul 5. doi: 10.1111/jcpp.13484. Epub ahead of print. PMID: 34225382.

Background: Eating disorders exhibit high comorbidity with other psychiatric disorders, most notably mood, substance use, and anxiety disorders. However, most studies examining psychiatric comorbidity are conducted in adolescents and adults. Therefore, the comorbidity among children living with eating disorders is unknown. The aim of this study was to characterize co-occurring psychiatric disorders with eating disorders in a US sample of children aged 9-10 years old utilizing the Adolescent Brain Cognitive Development study.

Methods: The analytic sample included 11,718 children aged 9-10 years. Anorexia nervosa, bulimia nervosa, binge eating disorder, and other specified feeding and eating disorder subtype diagnoses were examined. Statistical analyses were conducted using complex sampling. Odds ratios and 95% confidence intervals were calculated comparing the likelihood of being diagnosed for a psychiatric disorder when having an eating disorder, as compared to children without an eating disorder, children diagnosed with major depressive disorder, and children diagnosed with posttraumatic stress disorder using binary logistic regression.

Results: Co-occurring psychiatric disorders were substantially higher in children with eating disorders as compared to children without eating disorders, but not as compared to children diagnosed with major depressive disorder or posttraumatic stress disorder. The most common comorbidities for the eating disorder group were anxiety disorders (71.4%), attention deficit/hyperactivity disorder (47.9%), disruptive/impulse control disorders (45.0%), mood disorders (29.6%), and obsessive-compulsive disorder (28.8%), largely in line with previous research.

Conclusions: This study extends prior research finding high rates of comorbidity in eating disorders, specifically with anxiety, mood, and disruptive/impulse control disorders. Clinicians assessing for psychiatric disorders should be aware that eating disorders can occur in children 9 and 10 years old and are associated with severe comorbidity. Referrals for specialty mental health care should be considered.

Morphometry of the Lateral Orbitofrontal Cortex is Associated With Eating Dispositions in Early Adolescence: Findings From a Large Population-Based Study

Peter A Hall, John Best, James Danckert, Elliott A Beaton, Jessica Lee (2021). Morphometry of the Lateral Orbitofrontal Cortex is Associated With Eating Dispositions in Early Adolescence: Findings From a Large Population-Based Study, Social Cognitive and Affective Neuroscience, 2021, nsab084, https://doi.org/10.1093/scan/nsab084

Early adolescence is a critical period for eating behavior as children gain autonomy around food choice and peer influences increase in potency. From a neurodevelopmental perspective, significant structural changes take place in the prefrontal cortex during this time, including the orbitofrontal cortex (OFC), which is involved in socially contextualized decision making. We examined morphological features of the OFC in relation to food choice in a sample of 10,309 early adolescent children from the ABCD study. Structural parameters of the OFC and insula were examined for relationships with two important aspects of food choice: limiting consumption of fast/fried food and maximizing consumption of nutritious foods. Raw, partially and fully adjusted models were evaluated. Findings revealed that larger surface area of the lateral OFC was associated with higher odds of limiting fast/fried food consumption in raw (OR=1.07, CI:1.02,1.12, p=.002, pFDR=.012), partially adjusted (OR=1.11, CI:1.03,1.19, p=.004, pFDR=.024), and fully adjusted models (OR=1.11, CI:1.03,1.19, p=.006, pFDR=.036). In contrast, larger insula volume was associated with lower odds of maximizing healthy foods in raw (OR=0.94, CI:.91,0.97, p <.001, pFDR=.003) and partially adjusted (OR=0.93, CI: 0.88-0.98, p=.008, pFDR=.048) models. These findings refine understanding of the OFC as a network node implicated in socially mediated eating behavior.

Symptom-Based Profiling and Multimodal Neuroimaging of a Large Preteenage Population Identifies Distinct Obsessive-Compulsive Disorder-like Subtypes With Neurocognitive Differences

Wu X, Yu G, Zhang K, Feng J, Zhang J, Sahakian BJ, Robbins TW. Symptom-Based Profiling and Multimodal Neuroimaging of a Large Preteenage Population Identifies Distinct Obsessive-Compulsive Disorder-like Subtypes With Neurocognitive Differences. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Jul 2:S2451-9022(21)00175-0. doi: 10.1016/j.bpsc.2021.06.011. Epub ahead of print. PMID: 34224907.

Background: Obsessive-compulsive disorder (OCD) is characterized by both internalizing (anxiety) and externalizing (compulsivity) symptoms. Currently, little is known about their interrelationships and their relative contributions to disease heterogeneity. Our goal is to resolve affective and cognitive symptom heterogeneity related to internalized and externalized symptom dimensions by determining subtypes of children with OCD symptoms, and to identify any corresponding neural differences.

Methods: A total of 1269 children with OCD symptoms screened using the Child Behavior Checklist Obsessive-Compulsive Symptom scale and 3987 matched control subjects were obtained from the Adolescent Brain Cognitive Development (ABCD) Study. Consensus hierarchical clustering was used to cluster children with OCD symptoms into distinct subtypes. Ten neurocognitive task scores and 20 Child Behavior Checklist syndrome scales were used to characterize cognitive/behavioral differences. Gray matter volume, fractional anisotropy of major white matter fiber tracts, and functional connectivity among networks were used in case-control studies.

Results: We identified two subgroups with contrasting patterns in internalized and externalized dimensions. Group 1 showed compulsive thoughts and repeated acts but relatively low anxiety symptoms, whereas group 2 exhibited higher anxiety and perfectionism and relatively low repetitive behavior. Only group 1 had significant cognitive impairments and gray matter volume reductions in the bilateral inferior parietal lobe, precentral gyrus, and precuneus gyrus, and had white matter tract fractional anisotropy reductions in the corticostriatal fasciculus.

Conclusions: Children with OCD symptoms are heterogeneous at the level of symptom clustering and its underlying neural basis. Two subgroups represent distinct patterns of externalizing and internalizing symptoms, suggesting that anxiety is not its major predisposing factor. These results may have implications for the nosology and treatment of preteenage OCD.

Neurobiological antecedents of multisite pain in children

Kaplan CM, Schrepf A, Mawla I, Ichesco E, Boehnke KF, Beltz A, Foxen-Craft E, Puglia M, Tsodikov A, Williams DA, Hassett AL, Clauw DJ, Harte SE, Harris RE. (2021). Neurobiological antecedents of multisite pain in children. PAIN: July 02, 2021 – doi: 10.1097/j.pain.0000000000002431

Altered brain structure and function is evident in adults with multisite chronic pain. Although many such adults trace their pain back to childhood, it has been difficult to disentangle whether central nervous system alterations precede or are consequences of chronic pain. If the former is true, aberrant brain activity may identify children vulnerable to developing chronic pain later in life. We examined structural and functional brain magnetic resonance imaging metrics in a subset of children from the first two assessments of the Adolescent Brain and Cognitive Development (ABCD) Study. Children (ages 9-10) who were pain-free at baseline and then developed multisite pain one year later (n=115) were matched to control children who were pain-free at both timepoints (n=230). We analyzed brain structure (cortical thickness and gray matter volume) and function (spontaneous neural activity and functional connectivity). Results were deemed significant at the cluster level p < 0.05 false discovery rate corrected for multiple comparisons. At baseline, children who subsequently developed multisite pain had increased neural activity in superior parietal/primary somatosensory and motor cortices and decreased activity in the medial prefrontal cortex. They also exhibited stronger functional connectivity between the salience network, somatosensory and default mode network regions. No significant differences in brain structure were observed. Increased neural activity and functional connectivity between brain regions, consistent to that seen in adults with chronic pain, exist in children prior to developing multisite pain. These findings may represent a neural vulnerability to developing future chronic pain.

Concurrent and prospective associations between fitbit wearable-derived RDoC arousal and regulatory constructs and adolescent internalizing symptoms

Nelson BW, Flannery JE, Flournoy J, Duell N, Prinstein MJ, Telzer E. Concurrent and prospective associations between fitbit wearable-derived RDoC arousal and regulatory constructs and adolescent internalizing symptoms. J Child Psychol Psychiatry. 2021 Jun 29. doi: 10.1111/jcpp.13471. Epub ahead of print. PMID: 34184767.

Background: Adolescence is characterized by alterations in biobehavioral functioning, during which individuals are at heightened risk for onset of psychopathology, particularly internalizing disorders. Researchers have proposed using digital technologies to index daily biobehavioral functioning, yet there is a dearth of research examining how wearable metrics are associated with mental health.

Methods: We preregistered analyses using the Adolescent Brain Cognitive Development Study dataset using wearable data collection in 5,686 adolescents (123,862 person-days or 2,972,688 person-hours) to determine whether wearable indices of resting heart rate (RHR), step count, and sleep duration and variability in these measures were cross-sectionally associated with internalizing symptomatology. All models were also run controlling for age, sex, body mass index, socioeconomic status, and race. We then performed prospective analyses on a subset of this sample (n = 143) across 25 months that had Fitbit data available at baseline and follow-up in order to explore directionality of effects.

Results: Cross-sectional analyses revealed a small, yet significant, effect size (R2 = .053) that higher RHR, lower step count and step count variability, and greater variability in sleep duration were associated with greater internalizing symptoms. Cross-lagged panel model analysis revealed that there were no prospective associations between wearable variables and internalizing symptoms (partial R2 = .026), but greater internalizing symptoms and higher RHR predicted lower step count 25 months later (partial R2 = .010), while higher RHR also predicted lower step count variability 25 months later (partial R2 = .008).

Conclusions: Findings indicate that wearable indices concurrently associate with internalizing symptoms during early adolescence, while a larger sample size is likely required to accurately assess prospective or directional effects between wearable indices and mental health. Future research should capitalize on the temporal resolution provided by wearable devices to determine the intensive longitudinal relations between biobehavioral risk factors and acute changes in mental health.

Contemporary screen time usage among children 9-10-years-old is associated with higher body mass index percentile at 1-year follow-up: A prospective cohort study

Nagata JM, Iyer P, Chu J, Baker FC, Gabriel KP, Garber AK, Murray SB, Bibbins-Domingo K, Ganson KT (2021). Contemporary screen time usage among children 9-10-years-old is associated with higher body mass index percentile at 1-year follow-up: A prospective cohort study. Pediatr Obes. 2021 Jun 28:e12827. doi: 10.1111/ijpo.12827. Epub ahead of print. PMID: 34180585.

Objective: There is a paucity of prospective research exploring the relationship among contemporary screen time modalities (e.g., video streaming, video chatting, texting and social networking) and body mass index (BMI) percentile. The objective of this study was to determine the prospective associations between screen time behaviours in a large and demographically diverse population-based cohort of 9-10-year-old children and BMI percentile at 1-year follow-up.

Methods: We analyzed prospective cohort data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11 066). Multiple linear regression analyses were conducted to estimate associations between baseline screen time behaviours (exposure) and BMI percentile at 1-year follow-up, adjusting for race/ethnicity, sex, household income, parent education, depression, binge-eating disorder and baseline BMI percentile.

Results: Each additional hour of total screen time per week was prospectively associated with a 0.22 higher BMI percentile at 1-year follow-up (95% CI 0.10-0.34) after adjusting for covariates. When examining specific screen time behaviours, each additional hour of texting (B = 0.92, 95% CI 0.29-1.55), video chat (B = 0.72, 95% CI 0.09-1.36) and video games (B = 0.42, 95% CI 0.06-0.78) was significantly prospectively associated with higher BMI percentile.

Conclusions: Screen time is prospectively associated with a higher BMI percentile 1 year later among children 9-10 years old.

Brain structure is linked to the association between family environment and behavioral problems in children in the ABCD study

Gong, W., Rolls, E.T., Du, J. et al. (2021). Brain structure is linked to the association between family environment and behavioral problems in children in the ABCD study. Nat Commun 12, 3769 (2021). https://doi.org/10.1038/s41467-021-23994-0

Children’s behavioral problems have been associated with their family environments. Here, we investigate whether specific features of brain structures could relate to this link. Using structural magnetic resonance imaging of 8756 children aged 9-11 from the Adolescent Brain Cognitive Developmental study, we show that high family conflict and low parental monitoring scores are associated with children’s behavioral problems, as well as with smaller cortical areas of the orbitofrontal cortex, anterior cingulate cortex, and middle temporal gyrus. A longitudinal analysis indicates that psychiatric problems scores are associated with increased family conflict and decreased parental monitoring 1 year later, and mediate associations between the reduced cortical areas and family conflict, and parental monitoring scores. These results emphasize the relationships between the brain structure of children, their family environments, and their behavioral problems.

Meaningful Associations in the Adolescent Brain Cognitive Development Study

Dick AS, Lopez DA, Watts AL, Heeringa S, Reuter C, Bartsch H, Fan CC, Kennedy DN, Palmer C, Marshall A, Haist F, Hawes S, Nichols TE, Barch DM, Jernigan TL, Garavan H, Grant S, Pariyadath V, Hoffman E, Neale M, Stuart EA, Paulus MP, Sher KJ, Thompson WK. Meaningful Associations in the Adolescent Brain Cognitive Development Study. Neuroimage. 2021 Jun 17:118262. doi: 10.1016/j.neuroimage.2021.118262. Epub ahead of print. PMID: 34147629.

The Adolescent Brain Cognitive Development (ABCD) Study is the largest single-cohort prospective longitudinal study of neurodevelopment and children’s health in the United States. A cohort of n= 11,880 children aged 9-10 years (and their parents/guardians) were recruited across 22 sites and are being followed with in-person visits on an annual basis for at least 10 years. The study approximates the US population on several key sociodemographic variables, including sex, race, ethnicity, household income, and parental education. Data collected include assessments of health, mental health, substance use, culture and environment and neurocognition, as well as geocoded exposures, structural and functional magnetic resonance imaging (MRI), and whole-genome genotyping. Here, we describe the ABCD Study aims and design, as well as issues surrounding estimation of meaningful associations using its data, including population inferences, hypothesis testing, power and precision, control of covariates, interpretation of associations, and recommended best practices for reproducible research, analytical procedures and reporting of results.

Baseline brain function in the preadolescents of the ABCD Study

Chaarani, B., Hahn, S., Allgaier, N. et al. Baseline brain function in the preadolescents of the ABCD Study. Nat Neurosci (2021). https://doi.org/10.1038/s41593-021-00867-9

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Polygenic Risk Scores for Alcohol Involvement Relate to Brain Structure in Substance-Naïve Children: Results from the ABCD Study

Hatoum AS, Johnson EC, Baranger DAA, Paul SE, Agrawal A, Bogdan R (2021). Polygenic Risk Scores for Alcohol Involvement Relate to Brain Structure in Substance-Naïve Children: Results from the ABCD Study. Genes Brain Behav. 2021 Jun 6;e12756. doi: 10.1111/gbb.12756. Online ahead of print.

Background and aims: Brain imaging-derived structural correlates of alcohol involvement have largely been speculated to arise as a consequence of alcohol exposure. However, they may also reflect predispositional risk.

Methods: In substance naïve children of European ancestry who completed the baseline session of the Adolescent Brain Cognitive Development (ABCD) Study (n=3,013), mixed-effects models estimated whether polygenic risk scores (PRS) for Problematic Alcohol Use (PAU-PRS) and Drinks Per Week (DPW-PRS) are associated with magnetic resonance imaging-derived brain structure phenotypes (i.e., total and regional: cortical thickness, surface area and volume; subcortical volume; white matter volume, fractional anisotropy, mean diffusivity). Follow-up analyses evaluated whether any identified regions were also associated with polygenic risk among substance naïve children of African ancestry (n=898).

Results: After adjustment for multiple testing correction, polygenic risk for problematic alcohol use was associated with lower volume of the left frontal pole and greater cortical thickness of the right supramarginal gyrus (|βs|>0.009; ps<0.001; psfdr <0.046; r2 s < 0.004). PAU PRS and DPW PRS showed nominally significant associations with a host of other regional brain structure phenotypes (e.g., insula surface area and volume). None of these regions showed any, even nominal association among children of African ancestry.

Conclusions: Genomic liability to alcohol involvement may manifest as variability in brain structure during middle childhood prior to alcohol use initiation. Broadly, alcohol-related variability in brain morphometry may partially reflect predisposing genomic influence. Larger discovery GWASs and target samples of diverse ancestries are needed to determine whether observed associations may generalize across ancestral origins.

Evaluation of Attention-Deficit/Hyperactivity Disorder Medications, Externalizing Symptoms, and Suicidality in Children

Shoval G, Visoki E, Moore TM, DiDomenico GE, Argabright ST, Huffnagle NJ, Alexander-Bloch AF, Waller R, Keele L, Benton TD, Gur RE, Barzilay R (2021). Evaluation of Attention-Deficit/Hyperactivity Disorder Medications, Externalizing Symptoms, and Suicidality in Children. JAMA Netw Open. 2021;4(6):e2111342. June 4, 2021. doi:10.1001/jamanetworkopen.2021.11342

Importance
Childhood suicidality (ie, suicidal ideation or attempts) rates are increasing, and attention-deficit/hyperactivity disorder (ADHD) and externalizing symptoms are common risk factors associated with suicidality. More data are needed to describe associations of ADHD pharmacotherapy with childhood suicidality.

Objective
To investigate the associations of ADHD pharmacotherapy with externalizing symptoms and childhood suicidality.

Design, Setting, and Participants
In this cohort study, cross-sectional and 1-year-longitudinal associations were examined using data (collected during 2016-2019) from the Adolescent Brain Cognitive Development (ABCD) Study, a large, diverse US sample of children aged 9 to 11 years. Data analysis was performed from November to December 2020.

Exposures
Main and interaction associations of externalizing symptoms (hyperactivity ADHD symptoms, oppositional defiant, and conduct disorder symptoms) and ADHD medication treatment (methylphenidate and amphetamine derivatives, α-2-agonists, and atomoxetine) at baseline assessment.

Main Outcomes and Measures
Child-reported suicidality (past and present at baseline; current at longitudinal assessment). Covariates were age, sex, race/ethnicity, parents’ education, marital status, and concomitant child psychiatric pharmacotherapy (antidepressants and antipsychotics).

Results
Among 11 878 children at baseline assessment (mean [SD] age, 9.9 [0.6] years; 6196 boys [52.2%]; 8805 White [74.1%]), 1006 (8.5%) were treated with ADHD medication and 1040 (8.8%) reported past or current suicidality. Externalizing symptoms (median [range], 1 [0-29] symptom count) were associated with suicidality (for a change of 1 SD in symptoms, odds ratio [OR], 1.34; 95% CI, 1.26-1.42; P < .001), as was ADHD medication treatment (OR, 1.32; 95% CI, 1.06-1.64; P = .01). ADHD medication use was associated with less suicidality in children with more externalizing symptoms (significant symptom-by-medication interaction, B = −0.250; SE = 0.086; P = .004), such that for children who were not receiving ADHD medications, there was an association between more externalizing symptoms and suicidality (for a change of 1 SD in symptoms, OR, 1.42; 95% CI, 1.33-1.52; P < .001); however, for children who were receiving ADHD medication, there was no such association (OR, 1.15; 95% CI, 0.97-1.35; P = .10). The association with medication remained even when covarying for multiple confounders, including risk and protective factors for suicidality in ABCD, and was replicated in 1-year longitudinal follow-up. Sensitivity analyses matching participants with high numbers of externalizing symptoms taking and not taking ADHD medication treatment confirmed its association with less suicidality.

Conclusions and Relevance
These findings suggest that ADHD medication treatment is associated with less suicidality in children with substantial externalizing symptoms and may be used to inform childhood suicide prevention strategies.

Parents’ Perceived Neighborhood Safety and Children’s Cognitive Performance: Complexities by Race, Ethnicity, and Cognitive Domain

Assari S, Boyce S, Mistry R, Thomas A, Nicholson Jr HL, Cobb RJ, Cuevas AG, Lee DB, Bazargan M, Caldwell CH, Curry TJ, Zimmerman MA (2021). Parents’ Perceived Neighborhood Safety and Children’s Cognitive Performance: Complexities by Race, Ethnicity, and Cognitive Domain. Urban Science, 5(2), doi: 10.3390/urbansci5020046

Background: Aim: To examine racial/ethnic variations in the effect of parents’ subjective neighborhood safety on children’s cognitive performance. Methods: This cross-sectional study included 10,027 children from the Adolescent Brain Cognitive Development (ABCD) study. The exposure variable was parents’ subjective neighborhood safety. The outcomes were three domains of children’s cognitive performance: general cognitive performance, executive functioning, and learning/memory. We used mixed-effects regression models for data analysis. Results: Overall, parents’ subjective neighborhood safety was positively associated with children’s executive functioning, but not general cognitive performance or learning/memory. Higher parents’ subjective neighborhood safety had a more positive influence on the executive functioning of non-Hispanic White than Asian American children. Higher parents’ subjective neighborhood safety was associated with higher general cognitive performance and learning/memory for non-White children relative to non-Hispanic White children. Conclusion: The race/ethnicity of children moderates the association between neighborhood safety and cognitive performance. This becomes more complicated, as the patterns seem to differ across ethnicity and cognitive domains. It is unknown whether the observed racial/ethnic variations in the effect of neighborhood safety on cognitive performance are neighborhood characteristics such as residential segregation. Addressing neighborhood inequalities is needed if we wish to reduce racial/ethnic inequities in the cognitive development of children.

Race, Socioeconomic Status, and Cerebellum Cortex Fractional Anisotropy in Pre-Adolescents. Adolescents

Assari S, Boyce S (2021). Race, Socioeconomic Status, and Cerebellum Cortex Fractional Anisotropy in Pre-Adolescents. Adolescents. 2021 Jun;1(2):70-94. doi: 10.3390/adolescents1020007. Epub 2021 Mar 31.

Introduction: Cerebellum cortex fractional anisotropy is a proxy of the integrity of the cerebellum cortex. However, less is known about how it is shaped by race and socioeconomic status (SES) indicators such as parental education and household income.

Purpose: In a national sample of American pre-adolescents, this study had two aims: to test the effects of two SES indicators, namely parental education and household income, on cerebellum cortex fractional anisotropy, and to explore racial differences in these effects.

Methods: Using data from the Adolescent Brain Cognitive Development (ABCD) study, we analyzed the diffusion Magnetic Resonance Imaging (dMRI) data of 9565, 9-10-year-old pre-adolescents. The main outcomes were cerebellum cortex fractional anisotropy separately calculated for right and left hemispheres using dMRI. The independent variables were parental education and household income; both treated as categorical variables. Age, sex, ethnicity, and family marital status were the covariates. Race was the moderator. To analyze the data, we used mixed-effects regression models without and with interaction terms. We controlled for propensity score and MRI device.

Results: High parental education and household income were associated with lower right and left cerebellum cortex fractional anisotropy. In the pooled sample, we found significant interactions between race and parental education and household income, suggesting that the effects of parental education and household income on the right and left cerebellum cortex fractional anisotropy are all significantly larger for White than for Black pre-adolescents.

Conclusions: The effects of SES indicators, namely parental education and household income, on pre-adolescents’ cerebellum cortex microstructure and integrity are weaker in Black than in White families. This finding is in line with the Marginalization-related Diminished Returns (MDRs), defined as weaker effects of SES indicators for Blacks and other racial and minority groups than for Whites.

Responsible Use of Open-Access Developmental Data: The Adolescent Brain Cognitive Development (ABCD) Study

Simmons C, Conley MI, Gee DG, Baskin-Sommers A, Barch DM, Hoffman EA, Huber RS, Iacono WG, Nagel BJ, Palmer CE, Sheth CS, Sowell ER, Thompson WK, Casey BJ (2021). Responsible Use of Open-Access Developmental Data: The Adolescent Brain Cognitive Development (ABCD) Study. Psychol Sci. 2021 May 27;9567976211003564. doi: 10.1177/09567976211003564. Online ahead of print.

Household Income and Children’s Depressive Symptoms: Immigrants’ Diminished Returns

Assari S (2021). Household Income and Children’s Depressive Symptoms: Immigrants’ Diminished Returns. Int J Travel Med Glob Health. Fall 2020;8(4):157-164. doi: 10.34172/IJTMGH.2020.27.

Introduction: Relative to socially privileged groups, socially marginalized people experience weaker health effects of household income and other economic resources, a pattern known as Minorities’ Diminished Returns (MDRs). These MDRs are frequently seen in racial and ethnic minorities, but less is known about the relevance of such MDRs in immigrant families. To investigate the MDRs of household income on children’s depression as a function of immigration, we compared non-immigrant and immigrant children for the effect of household income on children’s depressive symptoms.

Methods: This cross-sectional study was conducted across multiple cities in the United States. Baseline data from the Adolescent Brain Cognitive Development (ABCD) study collected in 2018 was used. A total of 6,412 children between the ages of 9-10-year-old were included. The predictor variable was household income. The primary outcome was children’s depression measured by the Child Behavior Checklist (CBCL). Race, ethnicity, age, sex, parental marital status, parental employment, and financial difficulties were the covariates. Immigration status was the effect modifier.

Results: Overall, high household income was associated with lower children’s depressive symptoms. Immigration status showed a statistically significant interaction with household income on children’s depression. This interaction term suggested that high household income has a smaller protective effect against depression for immigrant children than non-immigrant children.

Conclusion: The protective effect of household income against children’s depression is diminished for immigrant than non-immigrant children.

Prediction of suicidal ideation and attempt in 9 and 10 year-old children using transdiagnostic risk features

Harman G, Kliamovich D, Morales AM, Gilbert S, Barch DM, Mooney MA, Feldstein Ewing SW, Fair DA, Nagel BJ (2021). Prediction of suicidal ideation and attempt in 9 and 10 year-old children using transdiagnostic risk features. PLoS One. 2021 May 25;16(5):e0252114. doi: 10.1371/journal.pone.0252114. eCollection 2021.

The objective of the current study was to build predictive models for suicidal ideation in a sample of children aged 9-10 using features previously implicated in risk among older adolescent and adult populations. This case-control analysis utilized baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study, collected from 21 research sites across the United States (N = 11,369). Several regression and ensemble learning models were compared on their ability to classify individuals with suicidal ideation and/or attempt from healthy controls, as assessed by the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version. When comparing control participants (mean age: 9.92±0.62 years; 4944 girls [49%]) to participants with suicidal ideation (mean age: 9.89±0.63 years; 451 girls [40%]), both logistic regression with feature selection and elastic net without feature selection predicted suicidal ideation with an AUC of 0.70 (CI 95%: 0.70-0.71). The random forest with feature selection trained to predict suicidal ideation predicted a holdout set of children with a history of suicidal ideation and attempt (mean age: 9.96±0.62 years; 79 girls [41%]) from controls with an AUC of 0.77 (CI 95%: 0.76-0.77). Important features from these models included feelings of loneliness and worthlessness, impulsivity, prodromal psychosis symptoms, and behavioral problems. This investigation provided an unprecedented opportunity to identify suicide risk in youth. The use of machine learning to examine a large number of predictors spanning a variety of domains provides novel insight into transdiagnostic factors important for risk classification.

 

Sex Differences in Psychopathology in a Large Cohort of Nine and Ten-Year-Olds

Loso HM, Dube SL, Chaarani B, Garavan H, Albaugh M, Ivanova M, Potter A (2021). Sex Differences in Psychopathology in a Large Cohort of Nine and Ten-Year-Olds. Psychiatry Res. 2021 May 24;302:114026. doi: 10.1016/j.psychres.2021.114026. Online ahead of print.

The current study quantified sex differences in psychopathology among 9 and 10-year-olds, examined sex differences among those with clinically elevated symptoms and investigated if puberty moderates the relationship between sex and psychopathology. Data were obtained from the Adolescent Brain and Cognitive Development (ABCD)® Study’s NDA data release 2.0. Results suggest that males have higher scores and greater frequency of clinically meaningful levels of psychopathology across several domains. Puberty did not interact with sex to affect psychopathology. However, as puberty advanced, the percentage of males and females with elevated scores increased.

Feasibility of Race by Sex Intersectionality Research on Suicidality in the Adolescent Brain Cognitive Development (ABCD) Study

Assari S, Boyce S, Bazargan M (2021). Feasibility of Race by Sex Intersectionality Research on Suicidality in the Adolescent Brain Cognitive Development (ABCD) Study. Children 2021, 8(6), 437; https://doi.org/10.3390/children8060437

Intersectional research on childhood suicidality requires studies with a reliable and valid measure of suicidality, as well as a large sample size that shows some variability of suicidality across sex by race intersectional groups. Objectives: We aimed to investigate the feasibility of intersectionality research on childhood suicidality in the Adolescent Brain Cognitive Development (ABCD) study. We specifically explored the reliability and validity of the measure, sample size, and variability of suicidality across sex by race intersectional groups. Methods: We used cross-sectional data (wave 1) from the ABCD study, which sampled 9013 non-Hispanic white (NHW) or non-Hispanic black (NHB) children between the ages of 9 and 10 between years 2016 and 2018. Four intersectional groups were built based on race and sex: NHW males (n = 3554), NHW females (n = 3158), NHB males (n = 1164), and NHB females (n = 1137). Outcome measure was the count of suicidality symptoms, reflecting all positive history and symptoms of suicidal ideas, plans, and attempts. To validate our measure, we tested the correlation between our suicidality measure and depression and Child Behavior Checklist (CBCL) sub-scores. Cronbach alpha was calculated for reliability across each intersectional group. We also compared groups for suicidality. Results: We observed some suicidality history in observed 3.2% (n = 101) of NHW females, 4.9% (n = 175) of NHW males, 5.4% (n = 61) of NHB females, and 5.8% (n = 68) of NHB males. Our measure’s reliability was acceptable in all race by sex groups (Cronbach alpha higher than 0.70+ in all intersectional groups). Our measure was valid in all intersectional groups, documented by a positive correlation with depression and CBCL sub-scores. We could successfully model suicidality across sex by race groups, using multivariable models. Conclusion: Given the high sample size, reliability, and validity of the suicidality measure, variability of suicidality, it is feasible to investigate correlates of suicidality across race by sex intersections in the ABCD study. We also found evidence of higher suicidality in NHB than NHW children in the ABCD study. The ABCD rich data in domains of social context, self-report, schools, parenting, psychopathology, personality, and brain imaging provides a unique opportunity to study intersectional differences in neural circuits associated with youth suicidality.

Parental Educational Attainment, the Superior Temporal Cortical Surface Area, and Reading Ability among American Children: A Test of Marginalization-Related Diminished Returns

Assari S, Boyce S, Bazargan M, Thomas A, Cobb RJ, Hudson D, Curry TJ, Nicholson, Jr. HL, Cuevas AG, Mistry R, Chavous TM, Caldwell CH, Zimmerman MA (2021). Parental Educational Attainment, the Superior Temporal Cortical Surface Area, and Reading Ability among American Children: A Test of Marginalization-Related Diminished Returns. Children 2021, 8(5), 412; https://doi.org/10.3390/children8050412

Background: Recent studies have shown that parental educational attainment is associated with a larger superior temporal cortical surface area associated with higher reading ability in children. Simultaneously, the marginalization-related diminished returns (MDRs) framework suggests that, due to structural racism and social stratification, returns of parental education are smaller for black and other racial/ethnic minority children compared to their white counterparts. Purpose: This study used a large national sample of 9–10-year-old American children to investigate associations between parental educational attainment, the right and left superior temporal cortical surface area, and reading ability across diverse racial/ethnic groups. Methods: This was a cross-sectional analysis that included 10,817 9–10-year-old children from the Adolescent Brain Cognitive Development (ABCD) study. Parental educational attainment was treated as a five-level categorical variable. Children’s right and left superior temporal cortical surface area and reading ability were continuous variables. Race/ethnicity was the moderator. To adjust for the nested nature of the ABCD data, mixed-effects regression models were used to test the associations between parental education, superior temporal cortical surface area, and reading ability overall and by race/ethnicity. Results: Overall, high parental educational attainment was associated with greater superior temporal cortical surface area and reading ability in children. In the pooled sample, we found statistically significant interactions between race/ethnicity and parental educational attainment on children’s right and left superior temporal cortical surface area, suggesting that high parental educational attainment has a smaller boosting effect on children’s superior temporal cortical surface area for black than white children. We also found a significant interaction between race and the left superior temporal surface area on reading ability, indicating weaker associations for Alaskan Natives, Native Hawaiians, and Pacific Islanders (AIAN/NHPI) than white children. We also found interactions between race and parental educational attainment on reading ability, indicating more potent effects for black children than white children. Conclusion: While parental educational attainment may improve children’s superior temporal cortical surface area, promoting reading ability, this effect may be unequal across racial/ethnic groups. To minimize the racial/ethnic gap in children’s brain development and school achievement, we need to address societal barriers that diminish parental educational attainment’s marginal returns for middle-class minority families. Social and public policies need to go beyond equal access and address structural and societal barriers that hinder middle-class families of color and their children. Future research should test how racism, social stratification, segregation, and discrimination, which shape the daily lives of non-white individuals, take a toll on children’s brains and academic development.

Association between Hippocampal Volume and Working Memory in 10,000+ 9–10-Year-Old Children: Sex Differences

Assari S, Boyce S, Jovanovic T (2021). Association between Hippocampal Volume and Working Memory in 10,000+ 9–10-Year-Old Children: Sex Differences. Children 2021, 8(5), 411; https://doi.org/10.3390/children8050411

Aim: This study tested sex differences in the association between hippocampal volume and working memory of a national sample of 9–10-year-old children in the US. As the hippocampus is functionally lateralized (especially in task-related activities), we explored the results for the right and the left hippocampus. Methods: This is a cross-sectional study using the Adolescent Brain Cognitive Development (ABCD) Study data. This analysis included baseline ABCD data (n = 10,093) of children between ages 9 and 10 years. The predictor variable was right and left hippocampal volume measured by structural magnetic resonance imaging (sMRI). The primary outcome, list sorting working memory, was measured using the NIH toolbox measure. Sex was the moderator. Age, race, ethnicity, household income, parental education, and family structure were the covariates. Results: In the overall sample, larger right (b = 0.0013; p < 0.001) and left (b = 0.0013; p < 0.001) hippocampal volumes were associated with higher children’s working memory. Sex had statistically significant interactions with the right (b = −0.0018; p = 0.001) and left (b = −0.0012; p = 0.022) hippocampal volumes on children’s working memory. These interactions indicated stronger positive associations between right and left hippocampal volume and working memory for females compared to males. Conclusion: While right and left hippocampal volumes are determinants of children’s list sorting working memory, these effects seem to be more salient for female than male children. Research is needed on the role of socialization, sex hormones, and brain functional connectivity as potential mechanisms that may explain the observed sex differences in the role of hippocampal volume as a correlate of working memory.

Prevalence of Perceived Racism and Discrimination Among US Children Aged 10 and 11 Years: The Adolescent Brain Cognitive Development (ABCD) Study

Nagata JM, Ganson KT, Sajjad OM, Benabou SE, Bibbins-Domingo K (2021). Prevalence of Perceived Racism and Discrimination Among US Children Aged 10 and 11 Years: The Adolescent Brain Cognitive Development (ABCD) Study. Research Letter, JAMA Pediatr. 2021 May 17. doi: 10.1001/jamapediatrics.2021.1022. Online ahead of print.

Research has consistently shown that racism is detrimental to the health of children, adolescents, and their families.1 These consequences range from higher infant mortality to poorer mental health and juvenile justice involvement.1 Despite the plethora of known adverse outcomes associated with racism among young people, little is known regarding the number of children who report that they experience racism and discrimination directly. Identifying the prevalence of racism and discrimination among a crucial developmental age group is imperative to curtail poor outcomes, adjust public health measures, and improve medical and mental health assessments and treatments. Therefore, the objective of this study was to assess the national prevalence of perceived racism and discrimination among 10- and 11-year-old children.

 

Associations of family income with cognition and brain structure in USA children: prevention implications

Tomasi D, Volkow ND (2021). Associations of family income with cognition and brain structure in USA children: prevention implications. Mol Psychiatry. 2021 May 14. doi: 10.1038/s41380-021-01130-0. Online ahead of print.

Poverty, as assessed by several socioeconomic (SES) factors, has been linked to worse cognitive performance and reduced cortical brain volumes in children. However, the relative contributions of the various SES factors on brain development and the mediating effects between cognition and brain morphometry have not been investigated. Here we used cross-sectional data from the ABCD Study to evaluate associations among various SES and demographic factors, brain morphometrics, and cognition and their reproducibility in two independent subsamples of 3892 children. Among the SES factors, family income (FI) best explained individual differences in cognitive test scores (stronger for crystallized than for fluid cognition), cortical volume (CV), and thickness (CT). Other SES factors that showed significant associations with cognition and brain morphometrics included parental education and neighborhood deprivation, but when controlling for FI, their effect sizes were negligible and their regional brain patterns were not reproducible. Mediation analyses showed that cognitive scores, which we used as surrogate markers of the children’s level of cognitive stimulation, partially mediated the association of FI and CT, whereas the mediations of brain morphometrics on the association of FI and cognition were not significant. These results suggest that lack of supportive/educational stimulation in children from low-income families might drive the reduced CV and CT. Thus, strategies to enhance parental supportive stimulation and the quality of education for children in low-income families could help counteract the negative effects of poverty on children’s brain development.

Widespread Positive Direct and Indirect Effects of Regular Physical Activity on the Developing Functional Connectome in Early Adolescence

Brooks SJ, Parks SM, Stamoulis C (2021). Widespread Positive Direct and Indirect Effects of Regular Physical Activity on the Developing Functional Connectome in Early Adolescence, Cerebral Cortex, 2021;, bhab126, https://doi.org/10.1093/cercor/bhab126

Adolescence is a period of profound but incompletely understood changes in the brain’s neural circuitry (the connectome), which is vulnerable to risk factors such as unhealthy weight, but may be protected by positive factors such as regular physical activity. In 5955 children (median age = 120 months; 50.86% females) from the Adolescent Brain Cognitive Development (ABCD) cohort, we investigated direct and indirect (through impact on body mass index [BMI]) effects of physical activity on resting-state networks, the backbone of the functional connectome that ubiquitously affects cognitive function. We estimated significant positive effects of regular physical activity on network connectivity, efficiency, robustness and stability (P ≤ 0.01), and on local topologies of attention, somatomotor, frontoparietal, limbic, and default-mode networks (P < 0.05), which support extensive processes, from memory and executive control to emotional processing. In contrast, we estimated widespread negative BMI effects in the same network properties and brain regions (P < 0.05). Additional mediation analyses suggested that physical activity could also modulate network topologies leading to better control of food intake, appetite and satiety, and ultimately lower BMI. Thus, regular physical activity may have extensive positive effects on the development of the functional connectome, and may be critical for improving the detrimental effects of unhealthy weight on cognitive health.

Sleep Disturbance Predicts Depression Symptoms in Early Adolescence: Initial Findings From the Adolescent Brain Cognitive Development Study

Goldstone A, Javitz HS, Claudatos SA, Buysse DJ, Hasler BP, Zambotti M, Clark DB, Franzen PL, Prouty DE, Colrain IM, Baker FC (2021). Sleep Disturbance Predicts Depression Symptoms in Early Adolescence: Initial Findings From the Adolescent Brain Cognitive Development Study. Journal of Adolescent Health. Volume 66, Issue 5, May 2020, Pages 567-574. doi.org/10.1016/j.jadohealth.2019.12.005

Purpose
The aim of the study was to investigate associations between sleep disturbances and mental health in adolescents.

Methods
Data are from a national sample of 11,670 U.S. participants (5,594 females, aged 9–10 years, 63.5% white) in the Adolescent Brain Cognitive Development study. Initial longitudinal analyses were conducted for a subset of the sample (n = 4,951). Measures of youth sleep disturbance (disorders of initiating and maintaining sleep, sleep–wake transition disorders, and disorders of excessive somnolence) and “typical” total sleep time (number of hours slept on most nights in the past 6 months) were obtained from the parent-report Sleep Disturbance Scale (Data Release 2.0). Parent-report measures of youth mental health (depression, internalizing, and externalizing behaviors) from the Child Behavior Checklist and typical screen time were included.

Results
At baseline, greater sleep disturbance and shorter total sleep time were associated with greater internalizing, externalizing, and depression scores. After controlling for baseline mental health symptoms, baseline sleep disturbance significantly predicted depression and internalizing and externalizing scores at 1-year follow-up. A significant interaction with sex indicated that the association between disorders of excessive somnolence and depression 1 year later was steeper for girls, compared with boys (p < .001; 95% confidence interval 1.04–3.45).

Conclusions
Sleep disturbances predicted future mental health, particularly depression in this young sample, highlighting the potential to harness sleep as a tool to mitigate the persistence of depression across early adolescence and potentially prevent an adolescent onset of major depressive disorder.

Amygdalar Activation as a Neurobiological Marker of Differential Sensitivity in the Effects of Family Rearing Experiences on Socioemotional Adjustment in Youths

Liu S, Oshri A, Kogan SM, Wickrama KAS, Sweet L (2021). Amygdalar Activation as a Neurobiological Marker of Differential Sensitivity in the Effects of Family Rearing Experiences on Socioemotional Adjustment in Youths. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 May 5;S2451-9022(21)00124-5. doi: 10.1016/j.bpsc.2021.04.017. Online ahead of print.

Background: Substantial heterogeneity exists in how rearing environments influence youths’ socio-emotional outcomes. This heterogeneity, as suggested by the biological sensitivity to context (BSCT) and the differential susceptibility (DST) theories, is associated with emotional reactivity patterns and underlying neural functions. The present study investigated amygdalar reactivity to emotional stimuli as a neural signature that amplified the influence of rearing environments on youths’ socio-emotional outcomes.

Methods: To increase replicability and generalizability, this investigation included two independent studies that methodologically complemented each other. Study I employed a large, national, and longitudinal dataset (the ABCD study; N=11,875). Study II used a community sample of youths (N=123) with multi-method and multi-reporter assessments.

Results: In Study I, high left amygdalar reactivity to positive stimuli significantly amplified the impact of parental warmth on youths’ prosocial behaviors. In Study II, left and right amygdala reactivity to positive stimuli significantly intensified the associations between family functioning and youths’ internalizing problems. These findings were consistent with the BSCT/DST hypothesis because significant socio-emotional differences were observed at both negative and positive extremes of rearing environments. Additionally, Study II partially supported the diathesis-stress hypothesis by showing significant differences in youths’ vulnerability to negative family environments. Specifically, left amygdalar response to negative stimuli exacerbated the associations between unbalanced family functioning and heightened internalizing/externalizing symptoms. Left amygdalar reactivity to positive stimuli intensified the link between unbalanced family functioning and elevated externalizing problems.

Conclusions: Among youths and adolescents, amygdalar emotional reactivity may serve as a biomarker of differential sensitivity to rearing environments.

A Researcher’s Guide to the Measurement and Modeling of Puberty in the ABCD Study ® at Baseline

Cheng TW, Magis-Weinberg L, Guazzelli Williamson V, Ladouceur CD, Whittle SL, Herting MM, Uban KA, Byrne M, Barendse MEA, Shirtcliff EA, Pfeifer JH (2021). A Researcher’s Guide to the Measurement and Modeling of Puberty in the ABCD Study ® at Baseline. Front Endocrinol (Lausanne). 2021 May 5;12:608575. doi: 10.3389/fendo.2021.608575. eCollection 2021.

The Adolescent Brain Cognitive Development℠ (ABCD) Study is an ongoing, diverse, longitudinal, and multi-site study of 11,880 adolescents in the United States. The ABCD Study provides open access to data about pubertal development at a large scale, and this article is a researcher’s guide that both describes its pubertal variables and outlines recommendations for use. These considerations are contextualized with reference to cross-sectional empirical analyses of pubertal measures within the baseline ABCD dataset by Herting, Uban, and colleagues (2021). We discuss strategies to capitalize on strengths, mitigate weaknesses, and appropriately interpret study limitations for researchers using pubertal variables within the ABCD dataset, with the aim of building toward a robust science of adolescent development.

Association of Local Variation in Neighborhood Disadvantage in Metropolitan Areas With Youth Neurocognition and Brain Structure

Hackman DA, Cserbik D, Chen J-C, Berhane K, Minaravesh V, McConnell R, Herting MM (2021). Association of Local Variation in Neighborhood Disadvantage in Metropolitan Areas With Youth Neurocognition and Brain Structure. JAMA Pediatr. 2021 May 3;e210426. doi: 10.1001/jamapediatrics.2021.0426. Online ahead of print.

Importance: Neighborhood disadvantage is an important social determinant of health in childhood and adolescence. Less is known about the association of neighborhood disadvantage with youth neurocognition and brain structure, and particularly whether associations are similar across metropolitan areas and are attributed to local differences in disadvantage.

Objective: To test whether neighborhood disadvantage is associated with youth neurocognitive performance and with global and regional measures of brain structure after adjusting for family socioeconomic status and perceptions of neighborhood characteristics, and to assess whether these associations (1) are pervasive or limited, (2) vary across metropolitan areas, and (3) are attributed to local variation in disadvantage within metropolitan areas.

Design, setting, and participants: This cross-sectional study analyzed baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study, a cohort study conducted at 21 sites across the US. Participants were children aged 9.00 to 10.99 years at enrollment. They and their parent or caregiver completed a baseline visit between October 1, 2016, and October 31, 2018.

Exposures: Neighborhood disadvantage factor based on US census tract characteristics.

Main outcomes and measures: Neurocognition was measured with the NIH Toolbox Cognition Battery, and T1-weighted magnetic resonance imaging was used to assess whole-brain and regional measures of structure. Linear mixed-effects models examined the association between neighborhood disadvantage and outcomes after adjusting for sociodemographic factors.

Results: Of the 11 875 children in the ABCD Study cohort, 8598 children (72.4%) were included in this analysis. The study sample had a mean (SD) age of 118.8 (7.4) months and included 4526 boys (52.6%). Every 1-unit increase in the neighborhood disadvantage factor was associated with lower performance on 6 of 7 subtests, such as Flanker Inhibitory Control and Attention (unstandardized Β = -0.5; 95% CI, -0.7 to -0.2; false discovery rate (FDR)-corrected P = .001) and List Sorting Working Memory (unstandardized Β = -0.7; 95% CI, -1.0 to -0.3; FDR-corrected P < .001), as well as on all composite measures of neurocognition, such as the Total Cognition Composite (unstandardized Β = -0.7; 95% CI, -0.9 to -0.5; FDR-corrected P < .001). Each 1-unit increase in neighborhood disadvantage was associated with lower whole-brain cortical surface area (unstandardized Β = -692.6 mm2; 95% CI, -1154.9 to -230.4 mm2; FDR-corrected P = .007) and subcortical volume (unstandardized Β = -113.9 mm3; 95% CI, -198.5 to -29.4 mm3; FDR-corrected P = .03) as well as with regional surface area differences, primarily in the frontal, parietal, and temporal lobes. Associations largely remained after adjusting for perceptions of neighborhood safety and were both consistent across metropolitan areas and primarily explained by local variation in each area.

Conclusions and relevance: This study found that, in the US, local variation in neighborhood disadvantage was associated with lower neurocognitive performance and smaller cortical surface area and subcortical volume in young people. The findings demonstrate that neighborhood disadvantage is an environmental risk factor for neurodevelopmental and population health and enhancing the neighborhood context is a promising approach to improving the health and development of children and adolescents.

Gene–environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach

Warrier V, Kwong ASF, Luo M, Dalvie S, Croft J, Sallis HM, Baldwin J, Munafo MR, Nievergelt CM, Grant AJ, Burgess S, Moore TM, Barzilay R, McIntosh A, van IJzendoorn MH, Cecil CAM (2021). Gene–environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach. The Lancet, Psychiatry, Vol 8, Issue 5, P373-386, May 01, 2021.  DOI:https://doi.org/10.1016/S2215-0366(20)30569-1.

Background
Childhood maltreatment is associated with poor mental and physical health. However, the mechanisms of gene–environment correlations and the potential causal effects of childhood maltreatment on health are unknown. Using genetics, we aimed to delineate the sources of gene–environment correlation for childhood maltreatment and the causal relationship between childhood maltreatment and health.

Methods
We did a genome-wide association study meta-analysis of childhood maltreatment using data from the UK Biobank (n=143 473), Psychiatric Genomics Consortium (n=26 290), Avon Longitudinal Study of Parents and Children (n=8346), Adolescent Brain Cognitive Development Study (n=5400), and Generation R (n=1905). We included individuals who had phenotypic and genetic data available. We investigated single nucleotide polymorphism heritability and genetic correlations among different subtypes, operationalisations, and reports of childhood maltreatment. Family-based and population-based polygenic score analyses were done to elucidate gene–environment correlation mechanisms. We used genetic correlation and Mendelian randomisation analyses to identify shared genetics and test causal relationships between childhood maltreatment and mental and physical health conditions.

Findings
Our meta-analysis of genome-wide association studies (N=185 414) identified 14 independent loci associated with childhood maltreatment (13 novel). We identified high genetic overlap (genetic correlations 0·24–1·00) among different maltreatment operationalisations, subtypes, and reporting methods. Within-family analyses provided some support for active and reactive gene–environment correlation but did not show the absence of passive gene–environment correlation. Robust Mendelian randomisation suggested a potential causal role of childhood maltreatment in depression (unidirectional), as well as both schizophrenia and ADHD (bidirectional), but not in physical health conditions (coronary artery disease, type 2 diabetes) or inflammation (C-reactive protein concentration).

Interpretation
Childhood maltreatment has a heritable component, with substantial genetic correlations among different operationalisations, subtypes, and retrospective and prospective reports of childhood maltreatment. Family-based analyses point to a role of active and reactive gene–environment correlation, with equivocal support for passive correlation. Mendelian randomisation supports a (primarily bidirectional) causal role of childhood maltreatment on mental health, but not on physical health conditions. Our study identifies research avenues to inform the prevention of childhood maltreatment and its long-term effects.

Association of adverse prenatal exposure burden with child psychopathology in the Adolescent Brain Cognitive Development (ABCD)

Roffman JL, Sipahi ED, Dowling KF, Hughes DE, Hopkinson CE, Lee H, Eryilmaz H, Cohen LS, Gilman J, Doyle AE, Dunn EC (2021). Association of adverse prenatal exposure burden with child psychopathology in the Adolescent Brain Cognitive Development (ABCD). StudyPLoS One. 2021 Apr 28;16(4):e0250235. doi: 10.1371/journal.pone.0250235. eCollection 2021.

Objective: Numerous adverse prenatal exposures have been individually associated with risk for psychiatric illness in the offspring. However, such exposures frequently co-occur, raising questions about their cumulative impact. We evaluated effects of cumulative adverse prenatal exposure burden on psychopathology risk in school-aged children.

Methods: Using baseline surveys from the U.S.-based Adolescent Brain and Cognitive Development (ABCD) Study (7,898 non-adopted, unrelated children from 21 sites, age 9-10, and their primary caregivers), we examined 8 retrospectively-reported adverse prenatal exposures in relation to caregiver-reported total and subscale Child Behavior Checklist (CBCL) scores. We also assessed cumulative effects of these factors on CBCL total as a continuous measure, as well as on odds of clinically significant psychopathology (CBCL total ≥60), in both the initial set and a separate ABCD sample comprising an additional 696 sibling pairs. Analyses were conducted before and after adjustment for 14 demographic and environmental covariates.

Results: In minimally and fully adjusted models, 6 exposures (unplanned pregnancy; maternal alcohol, marijuana, and tobacco use early in pregnancy; pregnancy complications; and birth complications) independently associated with significant but small increases in CBCL total score. Among these 6, none increased the odds of crossing the threshold for clinically significant symptoms by itself. However, odds of exceeding this threshold became significant with 2 exposures (OR = 1.86, 95% CI 1.47-2.36), and increased linearly with each level of exposure (OR = 1.39, 95% CI 1.31-1.47), up to 3.53-fold for ≥4 exposures versus none. Similar effects were observed in confirmatory analysis among siblings. Within sibling pairs, greater discordance for exposure load associated with greater CBCL total differences, suggesting that results were not confounded by unmeasured family-level effects.

Conclusion: Children exposed to multiple common, adverse prenatal events showed dose-dependent increases in broad, clinically significant psychopathology at age 9-10. Fully prospective studies are needed to confirm and elaborate upon this pattern.

Breastfeeding Duration Is Associated With Domain-Specific Improvements in Cognitive Performance in 9–10-Year-Old Children

Lopez DA, Foxe JJ, Mao Y, Thompson WK, Martin HJ, Freedman EG (2021). Breastfeeding Duration Is Associated With Domain-Specific Improvements in Cognitive Performance in 9–10-Year-Old Children. Front. Public Health, 26 April 2021 | https://doi.org/10.3389/fpubh.2021.657422

Significant immunological, physical and neurological benefits of breastfeeding in infancy are well-established, but to what extent these gains persist into later childhood remain uncertain. This study examines the association between breastfeeding duration and subsequent domain-specific cognitive performance in a diverse sample of 9–10-year-olds enrolled in the Adolescent Brain Cognitive Development (ABCD) Study®. The analyses included 9,116 children that attended baseline with their biological mother and had complete neurocognitive and breastfeeding data. Principal component analysis was conducted on data from an extensive battery of neurocognitive tests using varimax-rotation to extract a three-component model encompassing General Ability, Executive Functioning, and Memory. Propensity score weighting using generalized boosted modeling was applied to balance the distribution of observed covariates for children breastfed for 0, 1–6, 7–12, and more than 12 months. Propensity score-adjusted linear regression models revealed significant association between breastfeeding duration and performance on neurocognitive tests representing General Ability, but no evidence of a strong association with Executive Function or Memory. Benefits on General Ability ranged from a 0.109 (1–6 months) to 0.301 (>12 months) standardized beta coefficient difference compared to those not breastfed. Results indicate clear cognitive benefits of breastfeeding but that these do not generalize to all measured domains, with implications for public health policy as it pertains to nutrition during infancy.

Extracurricular Activities, Screen Media Activity, and Sleep May Be Modifiable Factors Related to Children’s Cognitive Functioning: Evidence From the ABCD Study®

Kirlic N, Colaizzi JM, Cosgrove KT, Cohen ZP, Yeh H-W, Breslin F, Morris AS, Aupperle RL, Singh MK, Paulus MP (2021). Extracurricular Activities, Screen Media Activity, and Sleep May Be Modifiable Factors Related to Children’s Cognitive Functioning: Evidence From the ABCD Study®. Child Dev. 2021 Apr 26. doi: 10.1111/cdev.13578. Online ahead of print. DOI: 10.1111/cdev.13578

This study used a machine learning framework in conjunction with a large battery of measures from 9,718 school-age children (ages 9-11) from the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study to identify factors associated with fluid cognitive functioning (FCF), or the capacity to learn, solve problems, and adapt to novel situations. The identified algorithm explained 14.74% of the variance in FCF, replicating previously reported socioeconomic and mental health contributors to FCF, and adding novel and potentially modifiable contributors, including extracurricular involvement, screen media activity, and sleep duration. Pragmatic interventions targeting these contributors may enhance cognitive performance and protect against their negative impact on FCF in children.

Multimodal brain predictors of current weight and weight gain in children enrolled in the ABCD study®

Adise S, Allgaier N, Laurent J, Hahn S, Chaarani B, Owens M, Yuan D, Nyugen P, Mackey S, Potter A, Garavan HP (2021). Multimodal brain predictors of current weight and weight gain in children enrolled in the ABCD study®. Developmental Cognitive Neuroscience, Volume 49, June 2021, 100948, https://doi.org/10.1016/j.dcn.2021.100948

Multimodal neuroimaging assessments were utilized to identify generalizable brain correlates of current body mass index (BMI) and predictors of pathological weight gain (i.e., beyond normative development) one year later. Multimodal data from children enrolled in the Adolescent Brain Cognitive Development Study® at 9-to-10-years-old, consisted of structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), resting state (rs), and three task-based functional (f) MRI scans assessing reward processing, inhibitory control, and working memory. Cross-validated elastic-net regression revealed widespread structural associations with BMI (e.g., cortical thickness, surface area, subcortical volume, and DTI), which explained 35% of the variance in the training set and generalized well to the test set (R2 = 0.27). Widespread rsfMRI inter- and intra-network correlations were related to BMI (R2train = 0.21; R2test = 0.14), as were regional activations on the working memory task (R2train = 0.20; (R2 test = 0.16). However, reward and inhibitory control tasks were unrelated to BMI. Further, pathological weight gain was predicted by structural features (Area Under the Curve (AUC)train = 0.83; AUCtest = 0.83, p < 0.001), but not by fMRI nor rsfMRI. These results establish generalizable brain correlates of current weight and future pathological weight gain. These results also suggest that sMRI may have particular value for identifying children at risk for pathological weight gain.

The association between latent trauma and brain structure in children

Jeong HJ, Durhan EL, Moore TM, Dupont RM, McDowell M, Cardenas-Iniguez C, Micciche ET, Berman MG, Lahey BB, Kaczkurkin AN (2021). The association between latent trauma and brain structure in children. Transl Psychiatry. 2021 Apr 24;11(1):240. doi: 10.1038/s41398-021-01357-z. DOI: 10.1038/s41398-021-01357-z