2022
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.

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.

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.

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. Dev Cogn Neurosci. 2022 Oct 17;58:101164. doi: 10.1016/j.dcn.2022.101164. Epub ahead of print. PMID: 36274574.

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.

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.