2022
Longitudinal Evidence of a Vicious Cycle Between Nucleus Accumbens Microstructure and Childhood Weight Gai

Rapuano KM, Berrian N, Baskin-Sommers A, Décarie-Spain L, Sharma S, Fulton S, Casey BJ, Watts R. Longitudinal Evidence of a Vicious Cycle Between Nucleus Accumbens Microstructure and Childhood Weight Gain. J Adolesc Health. 2022 Mar 2:S1054-139X(22)00002-7. doi: 10.1016/j.jadohealth.2022.01.002. Epub ahead of print. PMID: 35248457.

Purpose: Pediatric obesity is a growing public health concern. Previous work has observed diet to impact nucleus accumbens (NAcc) inflammation in rodents, measured by the reactive proliferation of glial cells. Recent work in humans has demonstrated a relationship between NAcc cell density-a proxy for neuroinflammation-and weight gain in youth; however, the directionality of this relationship in the developing brain and association with diet remains unknown.

Methods: Waist circumference (WC) and NAcc cell density were collected in a large cohort of children (n > 2,000) participating in the Adolescent Brain Cognitive Development (ABCD) Study (release 3.0) at baseline (9-10 y) and at a Year 2 follow-up (11-12 y). Latent change score modeling (LCSM) was used to disentangle contributions of baseline measures to two-year changes in WC percentile and NAcc cellularity. In addition, the role of NAcc cellularity in mediating the relationship between diet and WC percentile was assessed using dietary intake data collected at Year 2.

Results: LCSM indicates that baseline WC percentile influences change in NAcc cellularity and that baseline NAcc cell density influences change in WC percentile. NAcc cellularity was significantly associated with WC percentile at Year 2 and mediated the relationship between dietary fat consumption and WC percentile.

Conclusions: These results implicate a vicious cycle whereby NAcc cell density biases longitudinal changes in WC percentile and vice versa. Moreover, NAcc cell density may mediate the relationship between diet and weight gain in youth. These findings suggest that diet-induced inflammation of reward circuitry may lead to behavioral changes that further contribute to weight gain.

The role of perceived threats on mental health, social, and neurocognitive youth outcomes: A multicontextual, person-centered approach

Conley MI, Hernandez J, Salvati JM, Gee DG, Baskin-Sommers A. The role of perceived threats on mental health, social, and neurocognitive youth outcomes: A multicontextual, person-centered approach. Dev Psychopathol. 2022 Mar 2:1-22. doi: 10.1017/S095457942100184X. Epub ahead of print. PMID: 35232507.

Perceived threat in youth’s environments can elevate risk for mental health, social, and neurocognitive difficulties throughout the lifespan. However, few studies examine variability in youth’s perceptions of threat across multiple contexts or evaluate outcomes across multiple domains, ultimately limiting our understanding of specific risks associated with perceived threats in different contexts. This study examined associations between perceived threat in youth’s neighborhood, school, and family contexts at ages 9-10 and mental health, social, and neurocognitive outcomes at ages 11-12 within a large US cohort (N = 5525) enrolled in the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). Latent profile analysis revealed four distinct profiles: Low Threat in all contexts, Elevated Family Threat, Elevated Neighborhood Threat, and Elevated Threat in all contexts. Mixed-effect models and post hoc pairwise comparisons showed that youth in Elevated Threat profile had poorer mental health and social outcomes 2 years later. Youth in the Elevated Family Threat profile uniquely showed increased disruptive behavior symptoms, whereas youth in the Elevated Neighborhood Threat profile predominantly displayed increased sleep problems and worse neurocognitive outcomes 2 years later. Together, findings highlight the importance of considering perceptions of threat across multiple contexts to achieve a more nuanced developmental picture.

The pandemic’s toll on young adolescents: Prevention and intervention targets to preserve their mental health

O Kiss, et al. The Pandemic’s Toll on Young Adolescents: Prevention and Intervention Targets to Preserve Their Mental Health. Journal of Adolescent Health, Volume 70, Issue 3, March 2022, Pages 387-395. DOI: 10.1016/j.jadohealth.2021.11.023.  Related press release.

Reliability and Stability Challenges in ABCD Task fMRI Data

Kennedy JT, Harms MP, Korucuoglu O, Astafiev SV, Barch DM, Thompson WK, Bjork JM, Anokhin AP. Reliability and Stability Challenges in ABCD Task fMRI Data. Neuroimage. 2022 Mar 1:119046. doi: 10.1016/j.neuroimage.2022.119046. Epub ahead of print. PMID: 35245674.

Trait stability of measures is an essential requirement for individual differences research. Functional MRI has been increasingly used in studies that rely on the assumption of trait stability, such as attempts to relate task related brain activation to individual differences in behavior and psychopathology. However, recent research using adult samples has questioned the trait stability of task-fMRI measures, as assessed by test-retest correlations. To date, little is known about trait stability of task fMRI in children. Here, we examined within-session reliability and long-term stability of individual differences in task-fMRI measures using fMRI measures of brain activation provided by the Adolescent Brain Cognitive Development (ABCD) Study Release v4.0 as an individual’s average regional activity, using its tasks focused on reward processing, response inhibition, and working memory. We also evaluated the effects of factors potentially affecting reliability and stability. Reliability and stability (quantified as the ratio of non-scanner related stable variance to all variances) was poor in virtually all brain regions, with an average value of .088 and .072 for short term (within-session) reliability and long-term (between-session) stability, respectively, in regions of interest (ROIs) historically-recruited by the tasks. Only one reliability or stability value in ROIs exceeded the ‘poor’ cut-off of .4, and in fact rarely exceeded .2 (only 4.9%). Motion had a pronounced effect on estimated reliability/stability, with the lowest motion quartile of participants having a mean reliability/stability 2.5 times higher (albeit still ‘poor’) than the highest motion quartile. Poor reliability and stability of task-fMRI, particularly in children, diminishes potential utility of fMRI data due to a drastic reduction of effect sizes and, consequently, statistical power for the detection of brain-behavior associations. This essential issue urgently needs to be addressed through optimization of task design, scanning parameters, data acquisition protocols, preprocessing pipelines, and data denoising methods.

Bayesian interaction selection model for multi-modal neuroimaging data analysis

Zhao Y, Wu B, Kang J. Bayesian interaction selection model for multi-modal neuroimaging data analysis. Biometrics. 2022 Feb 27. doi: 10.1111/biom.13648. Epub ahead of print. PMID: 35220581.

Multi-modality or multi-construct data arise increasingly in functional neuroimaging studies to characterize brain activity under different cognitive states. Relying on those high-resolution imaging collections, it is of great interest to identify predictive imaging markers and inter-modality interactions with respect to behavior outcomes. Currently, most of the existing variable selection models do not consider predictive effects from interactions, and the desired higher-order terms can only be included in the predictive mechanism following a two-step procedure, suffering from potential mis-specification. In this paper, we propose a unified Bayesian prior model to simultaneously identify main effect features and inter-modality interactions within the same inference platform in the presence of high dimensional data. To accommodate the brain topological information and correlation between modalities, our prior is designed by compiling the intermediate selection status of sequential partitions in light of the data structure and brain anatomical architecture, so that we can improve posterior inference and enhance biological plausibility. Through extensive simulations, we show the superiority of our approach in main and interaction effects selection, and prediction under multi-modality data. Applying the method to the Adolescent Brain Cognitive Development (ABCD) study, we characterize the brain functional underpinnings with respect to general cognitive ability under different memory load conditions. This article is protected by copyright. All rights reserved.

Prenatal Selective Serotonin Reuptake Inhibitor Exposure, Depression, and Brain Morphology in Middle Childhood: Results From the ABCD Study

Moreau AL, Voss M, Hansen I, Paul SE, Barch DM, Rogers CE, Bogdan R. (2022, In Press). Prenatal Selective Serotonin Reuptake Inhibitor Exposure, Depression, and Brain Morphology in Middle Childhood: Results From the ABCD Study. Biological Psychiatry, Published: February 26, 2022, DOI:https://doi.org/10.1016/j.bpsgos.2022.02.005

Background
Prenatal selective serotonin reuptake inhibitor (SSRI) exposure has been inconsistently linked to depression, and little is known about neural correlates. We examined whether prenatal SSRI exposure is associated with depressive symptoms and brain structure during middle childhood.

Methods
Prenatal SSRI exposure (retrospective caregiver report), depressive symptoms (caregiver-reported Child Behavior Checklist), and brain structure (magnetic resonance imaging–derived subcortical volume; cortical thickness and surface area) were assessed in children (analytic ns = 5420–7528; 235 with prenatal SSRI exposure; 9–10 years of age) who completed the baseline Adolescent Brain Cognitive Development Study session. Linear mixed-effects models nested data. Covariates included familial, pregnancy, and child variables. Matrix spectral decomposition adjusted for multiple testing.

Results
Prenatal SSRI exposure was not independently associated with depression after accounting for recent maternal depressive symptoms. Prenatal SSRI exposure was associated with greater left superior parietal surface area (b = 145.3 mm2, p = .00038) and lateral occipital cortical thickness (b = 0.0272 mm, p = .0000079); neither was associated with child depressive symptoms. Child depression was associated with smaller global brain structure.

Conclusions
Our findings, combined with adverse outcomes of exposure to maternal depression and the utility of SSRIs for treating depression, suggest that risk for depression during middle childhood should not discourage SSRI use during pregnancy. Associations between prenatal SSRI exposure and brain structure were small in magnitude and not associated with depression. It will be important for future work to examine associations between prenatal SSRI exposure and depression through young adulthood, when risk for depression increases.

Hyperbolic discounting rates and risk for problematic alcohol use in youth enrolled in the Adolescent Brain and Cognitive Development study

Kohler RJ, Lichenstein SD, Yip SW. Hyperbolic discounting rates and risk for problematic alcohol use in youth enrolled in the Adolescent Brain and Cognitive Development study. Addiction Biology, First published: 23 February 2022 https://doi.org/10.1111/adb.13160

Adolescence is the peak period for the emergence of substance use, which can lead to long-term psychosocial, occupational and interpersonal complications. Ongoing large-scale, longitudinal, consortium initiatives, such as the Adolescent Brain and Cognitive Development (ABCD) study, offer unprecedented opportunities to elucidate key risk factors for problematic substance use in a well-powered sample and to examine how changes in risk factors relate to symptoms across time. Delay discounting has been proposed as a putative risk marker for early substance-use initiation and other forms of psychopathology. However, the extent to which other factors (e.g., socio-economic status and cognitive ability) influence discounting behaviour in young adolescents is not well established. The present study leverages data from the ABCD study (n = 11 045) to assess associations between core demographic and familial variables and delay discounting in youth—operationalized using hyperbolic discounting rates (k)—before the onset of significant psychopathology. Model estimates revealed significant effects of individual difference factors (e.g., sex and socio-economic status) and alcohol risk status (based on family history) on delay discounting. No significant differences were observed in the primary sample when comparing the presence of parent drug problems or prenatal drug exposures. These effects will require replication in later waves of ABCD. Nonetheless, these results provide support for delay discounting as a potential risk marker for problematic alcohol use and demonstrate a relationship between key demographic variables and adolescent discounting behaviour. Further, these results provide an empirical baseline from which developmental trajectories of delay discounting and substance use may be tracked throughout future waves of ABCD.

Altered resting fMRI spectral power in data-driven brain networks during development: A longitudinal study

Agcaoglu O, Wilson TW, Wang YP, Stephen JM, Fu Z, Calhoun VD. Altered resting fMRI spectral power in data-driven brain networks during development: A longitudinal study. J Neurosci Methods. 2022 Feb 23;372:109537. doi: 10.1016/j.jneumeth.2022.109537. Epub ahead of print. PMID: 35217109.

Background: Longitudinal studies provide a more precise measure of brain development over time, as they focus on within subject variability, as opposed to cross-sectional studies. This is especially important in children, where rapid brain development occurs, and inter-subject variability can be large. Tracking healthy brain development and identifying markers of typical development are also critically important to diagnose mental disorders at early ages.

New method: We track longitudinal changes in spectral power of time-courses using a unique non-binning approach assessed with group independent component analysis, in a large multi time-point resting state functional magnetic resonance imaging dataset (N = 124) containing healthy children from 8.2 to 17.6 years old (m=12.6) called the Developmental Chronnecto-Genomics study. We examined how eyes open (EO) and eyes closed (EC) resting states play a role in age-related spectral differences, as several studies have reported differences in these conditions.

Results: Typical brain development shows increased spectral power in low frequencies and decreased spectral power in high frequencies in as children grow and develop, for both the EO and EC conditions. In addition, we observed significant differences in power spectra between EO and EC and between sexes, mainly suggesting higher spectral power in females at middle and high frequencies. A replication analysis using the Adolescent Brain Cognitive Development data (N = 3371, mean age 9.9 years old) further supported this result, also showing general increases in low frequencies and decreases in higher frequencies, though some network level differences are present comparing to the main dataset.

Comparison with existing method: Our results indicate that spectral power changes significantly with typical development and our non-binning approach shows these changes with more detailed frequency resolution comparing to binning approaches. This is important as many studies reported an association of higher frequency power with brain disorders.

Conclusion: Our findings of decreased spectral power in the high frequencies with development may be a general marker of typical development., though this needs further investigation.

Exploring neural correlates of behavioral and academic resilience among children in poverty

Ellwood-Lowe ME, Irving CN, Bunge SA. Exploring neural correlates of behavioral and academic resilience among children in poverty. Dev Cogn Neurosci. 2022 Feb 22;54:101090. doi: 10.1016/j.dcn.2022.101090. Epub ahead of print. PMID: 35248821.

Children in poverty must contend with systems that do not meet their needs. We explored what, at a neural level, helps explain children’s resilience in these contexts. Lower coupling between lateral frontoparietal network (LFPN) and default mode network (DMN)-linked, respectively, to externally- and internally-directed thought-has previously been associated with better cognitive performance. However, we recently found the opposite pattern for children in poverty. Here, we probed ecologically-valid assessments of performance. In a pre-registered study, we investigated trajectories of network coupling over ages 9-13 and their relation to school grades and attention problems. We analyzed longitudinal data from ABCD Study (N = 8366 children at baseline; 1303 below poverty). The link between cognitive performance and grades was weaker for children in poverty, highlighting the importance of ecologically-valid measures. As predicted, higher LFPN-DMN connectivity was linked to worse grades and attentional problems for children living above poverty, while children below poverty showed opposite tendencies. This interaction between LFPN-DMN connectivity and poverty related to children’s grades two years later; however, it was attenuated when controlling for baseline grades and was not related to attention longitudinally. Together, these findings suggest network connectivity is differentially related to performance in real-world settings for children above and below poverty.

Clouding up cognition?: Secondhand cannabis and tobacco exposure related to cognitive functioning in youth

Wade NE, McCabe CJ, Wallace AL, Gonzalez MR, Hoh E, Infante M.A, Hernandez Mejia M, Haist F (In Press, 2022). Clouding up cognition?: Secondhand cannabis and tobacco exposure related to cognitive functioning in youth. Biological Psychiatry Global Open Science. Available online 22 February 2022, In Press, Journal Pre-proof, https://doi.org/10.1016/j.bpsgos.2022.01.010

Background
Increasing legalization of cannabis, in addition to longstanding rates of tobacco use, raise concerns for possible cognitive decrements from secondhand smoke or environmental exposure, though little research exists. We investigate the relation between cognition and secondhand and environmental cannabis and tobacco exposure in youth.

Methods
The Adolescent Brain Cognitive Development (ABCD) Study Year 2 Follow-Up (n=5,580; 48% Female) cognitive performance and secondhand or environmental cannabis or tobacco exposure data was used. Principal components analysis identified a global cognition factor. Linear mixed effects models assessed global cognition and individual cognitive task performance by cannabis and/or tobacco environmental exposure. Sociodemographics and other potential confounds were examined. P-values were adjusted using the false-discovery rate method.

Results
Global cognition was not related to any exposure group after testing corrections and considering confounds. Beyond covariates and family/site-level factors, secondhand tobacco was related to poorer visual memory (p=.02), and environmental tobacco was associated with poorer visuospatial (p=.02) and language skills (p=.008). Secondhand cannabis was related to cognition, but not after controlling for potential confounders (p>.05). Environmental cannabis was related to better oral reading (p=.01). Including covariates attenuated effect sizes.

Conclusions
Secondhand tobacco exposure was associated with poorer visual memory, while environmental tobacco exposure was related to poorer language and visuospatial skills. Secondhand cannabis was not related to cognition after controlling for sociodemographic factors, but environmental cannabis exposure was related to better reading. As this is the first known study of its kind and thus preliminary, secondhand cannabis should continue to be investigated to confirm results.

Classifying Conduct Disorder using a biopsychosocial model and machine learning method

Chan L, Simmons C, Tillem S, Conley M, Brazil IA, Baskin-Sommers A. Classifying Conduct Disorder using a biopsychosocial model and machine learning method. Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Feb 22:S2451-9022(22)00043-X. doi: 10.1016/j.bpsc.2022.02.004. Epub ahead of print. PMID: 35217219.

Background: Conduct Disorder (CD) is a common syndrome with far-reaching effects. Risk factors for the development of CD span social, psychological, and biological domains. Researchers note that predictive models of CD are limited if the focus is on a single risk factor or, even, a single domain. Machine learning methods are optimized for the extraction of trends across multi-domain data but have yet to be implemented in predicting the development of CD.

Methods: Social (e.g., family, income), psychological (e.g., psychiatric, neuropsychological), and biological (e.g., resting-state graph metrics) risk factors were measured using data from the baseline visit of the Adolescent Brain Cognitive DevelopmentSM Study when youth were 9-10-years-old (n = 2,368). Applying a feed-forward neural network machine learning method, risk factors were used to predict CD diagnoses two years later.

Results: A model with factors that included social, psychological, and biological domains outperformed models representing factors within any single domain, predicting the presence of a CD diagnosis with 91.18% accuracy. Within each domain, certain factors stood out in terms of their relationship to CD (social: lower parental monitoring, more aggression in the household, lower income; psychological: greater ADHD and ODD symptoms, worse crystallized cognition and card sorting performance; biological: disruptions in the topology of subcortical and frontoparietal networks).

Conclusions: The development of an accurate, sensitive, and specific predictive model of CD has the potential to aid in prevention and intervention efforts. Key risk factors for CD appear best characterized as reflecting unpredictable, impulsive, deprived, and emotional external and internal contexts.

Association of Genome-Wide Polygenic Scores for Multiple Psychiatric and Common Traits in Preadolescent Youths at Risk of Suicide

Yoonie Joo Y, Moon S-Y, Wang H-H, Kim H, Lee E-J, Hun Kim, J, Posner J, Ahn W-Y, Choi I, Kim J-W, Cha J. Association of Genome-Wide Polygenic Scores for Multiple Psychiatric and Common Traits in Preadolescent Youths at Risk of Suicide. JAMA Netw Open. February 21, 2022;5(2):e2148585. doi:10.1001/jamanetworkopen.2021.48585

Importance
Suicide is the second leading cause of death among youths worldwide, but no available means exist to identify the risk of suicide in this population.

Objective
To assess whether genome-wide polygenic scores for psychiatric and common traits are associated with the risk of suicide among preadolescent children and to investigate whether and to what extent the interaction between early life stress (a major environmental risk factor) and polygenic factors is associated with suicidal thoughts and behaviors among youths.

Design, Setting, and Participants
This cohort study analyzed the genotype-phenotype data of 11 869 preadolescent children aged 9 to 10 years from the Adolescent Brain and Cognitive Development study. Data were collected from September 1, 2016, to October 21, 2018, and analyzed from August 1, 2020, to January 3, 2021. Using machine learning approaches, genome-wide polygenic scores of 24 complex traits were estimated to investigate their phenome-wide associations and utility for assessing risk of suicidal thoughts and behaviors (suicidal ideation [active, passive, and overall] and suicide attempt).

Main Outcomes and Measures
Genome-wide polygenic scores were used to measure 24 traits, including psychiatric disorders, cognitive capacity, and personality and psychological characteristics. The Child Behavior Checklist was used to measure early life stress, and the Family Environment Scale was used to assess family environment. Suicidal ideation and suicide attempts were derived from the computerized version of the Kiddie Schedule for Affective Disorders and Schizophrenia.

Results
Among 11 869 preadolescent children in the US, complete data for phenotypic outcomes, genotypes, and covariates were available for 7140 participants in the multiethnic cohort (mean [SD] age, 9.9 [0.6] years; 3588 girls [50.3%]), including 925 participants with suicidal ideation and 63 participants with suicide attempts. Among those 7140 participants, 729 had African ancestry (self-reported race or ethnicity: 569 Black, 71 Hispanic, and 89 other), 276 had admixed American ancestry (self-reported race or ethnicity: 265 Hispanic, 3 White, and 8 other), 150 had East Asian ancestry (self-reported race or ethnicity: 67 Asian, 18 Hispanic, and 65 other), 5718 had European ancestry (self-reported race or ethnicity: 7 Asian, 39 Black, 1142 Hispanic, 3934 White, and 596 other), and 267 had other ancestries (self-reported race or ethnicity: 70 Asian, 13 Black, 126 Hispanic, 48 White, and 10 other). Three genome-wide polygenic scores were significantly associated (false discovery rate P < .05) with suicidal thoughts and behaviors among all participants: attention-deficit/hyperactivity disorder (odds ratio [OR], 1.12; 95% CI, 1.05-1.21; P = .001), schizophrenia (OR, 1.50; 95% CI, 1.17-1.93; P = .002), and general happiness (OR, 0.89; 95% CI, 0.83-0.96; P = .002). In the analysis including only children with European ancestry, 3 additional genome-wide polygenic scores with false discovery rate significance were associated with suicidal thoughts and behaviors: autism spectrum disorder (OR, 1.18; 95% CI, 1.06-1.31; P = .002), major depressive disorder (OR, 1.12; 95% CI, 1.04-1.21; P = .003), and posttraumatic stress disorder (OR, 1.12; 95% CI, 1.04-1.21; P = .004). A significant interaction between genome-wide polygenic scores and environment was found, with genetic risk factors for autism spectrum disorder and the level of early life stress associated with increases in the risk of overall suicidal ideation and overall suicidal thoughts and behaviors (OR, 1.20; 95% CI, 1.07-1.35; P = .002). A machine learning model using multitrait genome-wide polygenic scores and additional self-reported questionnaire data (Child Behavior Checklist and Family Environment Scale) produced a moderately accurate estimate of overall suicidal thoughts and behaviors (area under the receiver operating characteristic curve [AUROC], 0.77; 95% CI, 0.73-0.81; accuracy, 0.67) and suicidal ideation (AUROC, 0.76; 95% CI, 0.72-0.80; accuracy, 0.66) among children with European ancestry only. Among all children in the multiethnic cohort, the integrated model also outperformed the baseline model in estimating the risk of overall suicidal thoughts and behaviors (AUROC, 0.71; 95% CI, 0.67-0.75; accuracy, 0.68) and suicidal ideation (AUROC, 0.75; 95% CI, 0.71-0.78; accuracy, 0.67).

Conclusions and Relevance
In this cohort study of preadolescent youths in the US, higher genome-wide polygenic scores for psychiatric disorders, such as attention-deficit/hyperactivity disorder, autism spectrum disorder, posttraumatic stress disorder, and schizophrenia, were significantly associated with a greater risk of suicidal ideation and suicide attempt. The findings and quantitative models from this study may help to identify children with a high risk of suicide, potentially assisting with early screening, intervention, and prevention.

Parent-adolescent agreement in reported moderate-to-vigorous intensity physical activity during the COVID-19 pandemic

Nagata JM, Cortez CA, Iyer P, Dooley EE, Ganson KT, Conroy AA, Gabriel KP. Parent-adolescent agreement in reported moderate-to-vigorous intensity physical activity during the COVID-19 pandemic. BMC Public Health 22, 332 (2022). https://doi.org/10.1186/s12889-022-12530-4

Purpose
To describe the agreement between parent- and adolescent- reports of adolescent moderate-to-vigorous intensity physical activity (MVPA) and to determine sociodemographic factors associated with MVPA reporting differences during the COVID-19 pandemic.

Methods
We analyzed data collected in May 2020 from the Adolescent Brain Cognitive Development Study (ABCD, N = 4841), a U.S. prospective cohort study. We quantified past weekly adolescent MVPA levels as reported by the parent and adolescent (referent). Intra-class correlation coefficients (ICC) and Bland-Altman plots were used to examine the degree of agreement between parent- and adolescent- reports.

Results
When quantifying adolescent MVPA during the same recall period, median (p25, p75) MVPA (h∙wk.− 1) was 2.17 (0.00, 6.00) as reported by adolescents and 1.52 (0.29, 4.75) by parents with a mean difference of 4.89. Statistically significant differences in reports of MVPA were found in households with income > $75,000: on average, adolescents reported higher MVPA levels than their parents. Bland-Altman plots illustrated that, among adolescents reporting no or little MVPA, there was higher parent-adolescent agreement. However, among adolescents reporting high levels of MVPA, there was less agreement between the parent- and adolescent- reports.

Conclusions
Despite more time spent together at home during the pandemic, there was generally low agreement between parent- and adolescent- reports of adolescent MVPA. Future research could examine parent-adolescent agreement of MVPA within the context of device-based measures (e.g., accelerometers), determine reasons for differences in parent-adolescent reporting of MVPA, and inform interventions for improved parental involvement and monitoring of MVPA.

Companion Animals and Adolescent Stress and Adaptive Coping During the COVID-19 Pandemic

Mueller MK, King EK, Halbreich ED, Callina KS. Companion Animals and Adolescent Stress and Adaptive Coping During the COVID-19 Pandemic. Anthrozoös, Published online 11 Feb 2022, https://doi.org/10.1080/08927936.2022.2027093

The COVID-19 pandemic has resulted in significant social disruptions for youth caused by lockdowns, school closures, and a lack of in-person social interactions. Companion animals are prevalent in United States households and may provide a source of emotional support and motivation for youth to engage in adaptive coping behaviors during social challenges. The goals of this study were to assess if dog owners, non-dog pet owners, and non-pet owners differed in stress levels, positive affect, and use of adaptive coping strategies such as increased time outdoors, regular walking, and healthy behaviors. This study used data collected during the COVID-19 pandemic from the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study, a large, nationally representative dataset of American youth. In a cross-sectional sample of 6,069 adolescents, there were significant, but small, relationships between owning a non-dog pet and lower levels of positive affect, and both dog owners and non-dog pet owners reported higher perceived stress compared with non-pet owners. Dog ownership was associated with higher odds of using healthy coping strategies compared with non-pet owners, but this relationship was not significant when controlling for demographic variables. Dog owners reported higher odds of having a walking routine and spending time outdoors compared with non-pet owners. Overall, the results suggest no buffering effect of pet ownership on youth mental wellbeing, but dog ownership is associated with some healthy coping behaviors linked to walking.

Measuring Retention within the Adolescent Brain Cognitive Development (ABCD)SM Study

Feldstein Ewing SW, Dash GF, Thompson WK, Reuter C, Diaz VG, Anokhin A, Chang L, Cottler LB, Dowling GJ, LeBlanc K, Zucker RA, Tapert SF, Brown SA, Garavan H. (2022). Measuring Retention within the Adolescent Brain Cognitive Development (ABCD)SM Study. Developmental Cognitive Neuroscience, Volume 54, April 2022, 101081.

The Adolescent Brain Cognitive Development (ABCD)SM study aims to retain a demographically diverse sample of youth and one parent across 21 sites throughout its 10-year protocol while minimizing selective (systematic) attrition. To evaluate the effectiveness of these efforts, the ABCD Retention Workgroup (RW) has employed a data-driven approach to examine, track, and intervene via three key metrics: (1) which youth completed visits late; (2) which youth missed visits; (3) which youth withdrew from the study. The RW actively examines demographic (race, education level, family income) and site factors (visit satisfaction, distance from site, and enrollment in ancillary studies) to strategize efforts that will minimize disengagement and loss of participating youth and parents. Data showed that the most robust primary correlates of late visits were distance from study site, race, and parental education level. Race, lower parental education level, parental employment status, and lower family income were associated with higher odds of missed visits, while being enrolled in one of the ancillary studies was associated with lower odds of missed visits. Additionally, it appeared that parents who were primary Spanish speakers withdrew at slightly higher rates. These findings provide insight into future targets for proactive retention efforts by the ABCD RW.

Multivariate, Transgenerational Associations of the COVID-19 Pandemic Across Minoritized and Marginalized Communities

Yip SW, Jordan A, Kohler RJ, Holmes A, Bzdok D. Multivariate, Transgenerational Associations of the COVID-19 Pandemic Across Minoritized and Marginalized Communities. JAMA Psychiatry. Published online February 9, 2022. doi:10.1001/jamapsychiatry.2021.4331

Importance
The experienced consequences of the COVID-19 pandemic have diverged across individuals, families, and communities, resulting in inequity within a host of factors. There is a gap of quantitative evidence about the transgenerational impacts of these experiences and factors.

Objective
To identify baseline predictors of COVID-19 experiences, as defined by child and parent report, using a multivariate pattern-learning framework from the Adolescent Brain and Cognitive Development (ABCD) cohort.

Design, Setting, and Participants
ABCD is an ongoing prospective longitudinal study of child and adolescent development in the United States including 11 875 youths, enrolled at age 9 to 10 years. Using nationally collected longitudinal profiling data from 9267 families, a multivariate pattern-learning strategy was developed to identify factor combinations associated with transgenerational costs of the ongoing COVID-19 pandemic. ABCD data (release 3.0) collected from 2016 to 2020 and released between 2019 and 2021 were analyzed in combination with ABCD COVID-19 rapid response data from the first 3 collection points (May-August 2020).

Exposures
Social distancing and other response measures imposed by COVID-19, including school closures and shutdown of many childhood recreational activities.

Main Outcomes and Measures
Mid–COVID-19 experiences as defined by the ABCD’s parent and child COVID-19 assessments.

Results
Deep profiles from 9267 youth (5681 female [47.8%]; mean [SD] age, 119.0 [7.5] months) and their caregivers were quantitatively examined. Enabled by a pattern-learning analysis, social determinants of inequity, including family structure, socioeconomic status, and the experience of racism, were found to be primarily associated with transgenerational impacts of COVID-19, above and beyond other candidate predictors such as preexisting medical or psychiatric conditions. Pooling information across more than 17 000 baseline pre–COVID-19 family indicators and more than 280 measures of day-to-day COVID-19 experiences, non-White (ie, families who reported being Asian, Black, Hispanic, other, or a combination of those choices) and/or Spanish-speaking families were found to have decreased resources (mode 1, canonical vector weight [CVW] = 0.19; rank 5 of 281), escalated likelihoods of financial worry (mode 1, CVW = −0.20; rank 4), and food insecurity (mode 1, CVW = 0.21; rank 2), yet were more likely to have parent-child discussions regarding COVID-19–associated health and prevention issues, such as handwashing (mode 1, CVW = 0.14; rank 9), conserving food or other items (mode 1, CVW = 0.21; rank 1), protecting elderly individuals (mode 1, CVW = 0.11; rank 21), and isolating from others (mode 1, CVW = 0.11; rank 23). In contrast, White families (mode 1, CVW = −0.07; rank 3), those with higher pre–COVID-19 income (mode 1, CVW = −0.07; rank 5), and presence of a parent with a postgraduate degree (mode 1, CVW = −0.06; rank 14) experienced reduced COVID-19–associated impact. In turn, children from families experiencing reduced COVID-19 impacts reported longer nighttime sleep durations (mode 1, CVW = 0.13; rank 14), less difficulties with remote learning (mode 2, CVW = 0.14; rank 7), and decreased worry about the impact of COVID-19 on their family’s financial stability (mode 1, CVW = 0.134; rank 13).

Conclusions and Relevance
The findings of this study indicate that community-level, transgenerational intervention strategies may be needed to combat the disproportionate burden of pandemics on minoritized and marginalized racial and ethnic populations.

Causal effects of psychostimulants on neural connectivity: a mechanistic, randomized clinical trial

Wang Y, Kessel E, Lee S, Hong S, Raffanello E, Hulvershorn LA, Margolis A, Peterson BS, Posner, J. Causal effects of psychostimulants on neural connectivity: a mechanistic, randomized clinical trial. The Journal of Child Psychology and Psychiatry, 09 Feb 2022, https://doi.org/10.1111/jcpp.13585.

Background
Psychostimulants are frequently used to treat attention-deficit/hyperactivity disorder (ADHD), but side effects are common leading to many patients discontinuing treatment. Identifying neural mechanisms by which psychostimulants attenuate symptoms may guide the development of more refined and tolerable therapeutics.

Methods
We conducted a 12-week, randomized, placebo-controlled trial (RCT) of a long-acting amphetamine, lisdexamfetamine (LDEX), in patients with ADHD, ages 6–25 years old. Of the 58 participants who participated in the RCT, 49 completed pre- and post-RCT magnetic resonance imaging scanning with adequate data quality. Healthy controls (HCs; n = 46) were included for comparison. Treatment effects on striatal and thalamic functional connectivity (FC) were identified using static (time-averaged) and dynamic (time-varying) measures and then correlated with symptom improvement. Analyses were repeated in independent samples from the Adolescent Brain Cognitive Development study (n = 103) and the ADHD-200 Consortium (n = 213).

Results
In 49 participants (25 LDEX; 24 Placebo), LDEX increased static and decreased dynamic FC (DFC). However, only DFC was associated with the therapeutic effects of LDEX. Additionally, at baseline, DFC was elevated in unmedicated-ADHD participants relative to HCs. Independent samples yielded similar findings – ADHD was associated with increased DFC, and psychostimulants with reduced DFC. Static FC findings were inconsistent across samples.

Conclusions
Changes in dynamic, but not static, FC were associated with the therapeutic effects of psychostimulants. While prior research has focused on static FC, DFC may offer a more reliable target for new ADHD interventions aimed at stabilizing network dynamics, though this needs confirmation with subsequent investigations.

Resilience to COVID-19: Socioeconomic Disadvantage Associated With Positive Caregiver–Youth Communication and Youth Preventative Actions

Marshall AT, Hackman DA, Baker FC, Breslin FJ, Brown SA, Dick AS, Gonzalez MR, Guillaume M, Kiss O, Lisdahl KM, McCabe CJ, Pelham III WE, Sheth C, Tapert SF, Van Rinsveld A, Wade NE, Sowell ER. Resilience to COVID-19: Socioeconomic Disadvantage Associated With Positive Caregiver–Youth Communication and Youth Preventative Actions. Front. Public Health, 09 February 2022 | https://doi.org/10.3389/fpubh.2022.734308

Socioeconomic disadvantage is associated with larger COVID-19 disease burdens and pandemic-related economic impacts. We utilized the longitudinal Adolescent Brain Cognitive Development Study to understand how family- and neighborhood-level socioeconomic disadvantage relate to disease burden, family communication, and preventative responses to the pandemic in over 6,000 youth-caregiver dyads. Data were collected at three timepoints (May–August 2020). Here, we show that both family- and neighborhood-level disadvantage were associated with caregivers’ reports of greater family COVID-19 disease burden, less perceived exposure risk, more frequent caregiver-youth conversations about COVID-19 risk/prevention and reassurance, and greater youth preventative behaviors. Families with more socioeconomic disadvantage may be adaptively incorporating more protective strategies to reduce emotional distress and likelihood of COVID-19 infection. The results highlight the importance of caregiver-youth communication and disease-preventative practices for buffering the economic and disease burdens of COVID-19, along with policies and programs that reduce these burdens for families with socioeconomic disadvantage.

Classification of suicidal thoughts and behaviour in children: results from penalised logistic regression analyses in the Adolescent Brain Cognitive Development study

van Velzen LS, Toenders YJ, Avila-Parcet A, Dinga R, Rabinowitz JA, Campos AI, Jahanshad N, Rentería ME, Schmaal L. Classification of suicidal thoughts and behaviour in children: results from penalised logistic regression analyses in the Adolescent Brain Cognitive Development study. Br J Psychiatry. 2022 Feb 9:1-9. doi: 10.1192/bjp.2022.7. Epub ahead of print. PMID: 35135639.

Background: Despite efforts to predict suicide risk in children, the ability to reliably identify who will engage in suicide thoughts or behaviours has remained unsuccessful.

Aims: We apply a novel machine-learning approach and examine whether children with suicide thoughts or behaviours could be differentiated from children without suicide thoughts or behaviours based on a combination of traditional (sociodemographic, physical health, social-environmental, clinical psychiatric) risk factors, but also more novel risk factors (cognitive, neuroimaging and genetic characteristics).

Method: The study included 5885 unrelated children (50% female, 67% White, 9-11 years of age) from the Adolescent Brain Cognitive Development (ABCD) study. We performed penalised logistic regression analysis to distinguish between: (a) children with current or past suicide thoughts or behaviours; (b) children with a mental illness but no suicide thoughts or behaviours (clinical controls); and (c) healthy control children (no suicide thoughts or behaviours and no history of mental illness). The model was subsequently validated with data from seven independent sites involved in the ABCD study (n = 1712).

Results: Our results showed that we were able to distinguish the suicide thoughts or behaviours group from healthy controls (area under the receiver operating characteristics curve: 0.80 child-report, 0.81 for parent-report) and clinical controls (0.71 child-report and 0.76-0.77 parent-report). However, we could not distinguish children with suicidal ideation from those who attempted suicide (AUROC: 0.55-0.58 child-report; 0.49-0.53 parent-report). The factors that differentiated the suicide thoughts or behaviours group from the clinical control group included family conflict, prodromal psychosis symptoms, impulsivity, depression severity and history of mental health treatment.

Conclusions: This work highlights that mostly clinical psychiatric factors were able to distinguish children with suicide thoughts or behaviours from children without suicide thoughts or behaviours. Future research is needed to determine if these variables prospectively predict subsequent suicidal behaviour.

Associations between social behaviors and experiences with neural correlates of implicit emotion regulation in middle childhood

Geckeler KC, Barch DM, Karcher NR. Associations between social behaviors and experiences with neural correlates of implicit emotion regulation in middle childhood. Neuropsychopharmacology. 2022 Feb 8. doi: 10.1038/s41386-022-01286-5. Epub ahead of print. PMID: 35136189.

Emotion regulation is essential for successful social interactions and function, which are important aspects of middle childhood. The current study is one of the first to examine associations between neural correlates of implicit emotion regulation and indices of social behavior and experience during late middle childhood. We examined neural activation during the implicit emotion regulation condition of the Emotional N-back task using data from 8987 9- to 11-year-olds from the Adolescent Brain Cognitive Development℠ study. The brain regions assessed included areas linked to social cognition, social behavior, and emotion recognition, including the amygdala, insula, middle temporal gyrus, and inferior parietal lobe. Greater number of close friends was associated with significantly higher activation of the fusiform gyrus, insula, temporoparietal junction, inferior parietal lobe, and superior temporal gyrus during implicit emotion regulation. Greater reciprocal social impairments were linked to decreased fusiform gyrus activation during implicit emotion regulation. More experiences of discrimination were associated with a significantly lower activation in the middle temporal gyrus during implicit emotion regulation. This study provides evidence that both positive and negative indices of children’s social experiences and behaviors are associated with neural correlates of implicit emotion regulation during late middle childhood. These findings suggest that both positive and negative indices of social behavior and experience, including those within and not within the youth’s control, are associated with generally unique neural correlates during implicit emotion regulation.

Associations between potentially traumatic events and psychopathology among preadolescents in the Adolescent Brain and Cognitive Development Study®

Thompson EL, Lever NA, Connors KM, Cloak CC, Reeves G, Chang L. Associations between potentially traumatic events and psychopathology among preadolescents in the Adolescent Brain and Cognitive Development Study®. J Trauma Stress. 2022 Feb 8. doi: 10.1002/jts.22793. Epub ahead of print. PMID: 35132700.

The current cross-sectional study aimed to extend the literature on childhood adversity by examining the unique associations between potentially traumatic events (PTEs) and a range of mental health concerns, including domain-specific versus comorbid concerns. Participants were 11,877 preadolescents (47.8% female, 15.0% Black, 20.3% Hispanic/Latinx, Mage = 9.5 years) taking part in the Adolescent Brain and Cognitive Development (ABCD) Study® . The Kiddie Schedule for Affective Disorders and Schizophrenia was used to measure PTEs and caregiver- and child-reported mental health concerns. Adjusted odds ratios (aORs) were used for the outcomes of interest. Overall, PTEs were consistently associated with increased odds of experiencing comorbid posttraumatic stress disorder (PTSD), internalizing disorders, and externalizing disorders, significant AORs = 1.34-4.30, after accounting for children’s experiences of other PTEs and polyvictimization. In contrast, PTEs were generally not associated with meeting the criteria for diagnoses within only one domain (i.e., internalizing-only or externalizing-only diagnoses). We also found PTEs to be differentially related to the various mental health outcomes. In particular, witnessing domestic violence was consistently associated with children’s psychopathology. Other PTEs, such as witnessing community violence, were not associated with children’s psychopathology in the final model. Associations between PTEs and mental health concerns did not differ as a function of sex. Overall, the results support the notion that PTEs are associated with comorbid concerns rather than individual disorders. These findings have important implications for the screening of PTEs, continued research on the conceptualization of traumatic stress, and the importance of accounting for comorbidities across mental health domains.

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

Johnson, E.I., Planalp, E.M. & Poehlmann-Tynan, J. Parental Arrest and Child Behavior: Differential Role of Executive Functioning among Racial Subgroups. J Child Fam Stud (2022). https://doi.org/10.1007/s10826-022-02251-y

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

Structural brain measures among children with and without ADHD in the Adolescent Brain and Cognitive Development Study cohort: a cross-sectional US population-based study

Bernanke J, Luna A, Chang l, Bruno E, Dworkin J, Posner J (2022). Structural brain measures among children with and without ADHD in the Adolescent Brain and Cognitive Development Study cohort: a cross-sectional US population-based study, The Lancet Psychiatry, Feb 7, 2022, DOI:https://doi.org/10.1016/S2215-0366(21)00505-8.

Background
Structural neuroimaging research has identified a variety of abnormalities in cortical and subcortical structures in children with ADHD. However, studies to date have not employed large, non-referred samples, complete with data on potential confounding variables. Here, we tested for differences in structural MRI measures among children with and without ADHD using data from the Adolescent Brain and Cognitive Development (ABCD) Study, the largest paediatric brain imaging study in the USA.

Methods
In this cross-sectional study, we used baseline demographic, clinical, and neuroimaging data from the ABCD Study, which recruited children aged 9–10 years between Sept 1, 2016, and Aug 31, 2018, representative of the sociodemographic features of the US population. ADHD was diagnosed by parent report of symptoms. Neuroimaging data underwent centralised quality control and processing by the ABCD team. Linear mixed effects models were used to estimate Cohen’s d values associated with ADHD for 79 brain measures of cortical thickness, cortical area, and subcortical volume. We used a novel simulation strategy to assess the ability to detect significant effects despite potential diagnostic misclassification.

Findings
Our sample included 10 736 participants (5592 boys, 5139 girls; 5692 White, 2165 Hispanic, 1543 Black, 221 Asian, and 1100 of other race or ethnicity), of whom, 949 met the criteria for ADHD and 9787 did not. In the full model, which included potential confounding variables selected a priori, we found only 11 significant differences across the 79 brain measures after false discovery rate correction, all indicating reductions in brain measures among participants with ADHD. Cohen’s d values were small, ranging from −0·11 to −0·06, and were not meaningfully changed by using a more restrictive comparison group or alternative diagnostic methods. Simulations indicated adequate statistical power to detect differences even if there was substantial diagnostic misclassification.

Interpretation
In a sample representative of the general population, children aged 9–10 years with ADHD differed only modestly on structural brain measures from their unaffected peers. Future studies might need to incorporate other MRI modalities, novel statistical approaches, or alternative diagnostic classifications, particularly for research aimed at developing ADHD diagnostic biomarkers.

Discovery of genomic loci of the human cerebral cortex using genetically informed brain atlases

Makowski C, Van Der Meer D, Dong W, Wang H, Wu Y, Zou J, Liu C, Rosenthal SB, Hagler Jr., Fan CC, Kremen WS, Andreassen OA, Jernigan TL, Dale AM, Zhang K, Visscher PM, Yang J, Chen C. DJ. Discovery of genomic loci of the human cerebral cortex using genetically informed brain atlases. Science, Feb 3, 2022, Vol 375, Issue 6580, pp. 522-528, DOI: 10.1126/science.abe8457

To determine the impact of genetic variants on the brain, we used genetically informed brain atlases in genome-wide association studies of regional cortical surface area and thickness in 39,898 adults and 9136 children. We uncovered 440 genome-wide significant loci in the discovery cohort and 800 from a post hoc combined meta-analysis. Loci in adulthood were largely captured in childhood, showing signatures of negative selection, and were linked to early neurodevelopment and pathways associated with neuropsychiatric risk. Opposing gradations of decreased surface area and increased thickness were associated with common inversion polymorphisms. Inferior frontal regions, encompassing Broca’s area, which is important for speech, were enriched for human-specific genomic elements. Thus, a mixed genetic landscape of conserved and human-specific features is concordant with brain hierarchy and morphogenetic gradients.

Age-related changes and longitudinal stability of individual differences in ABCD Neurocognition measures

Anokhin AP, Luciana M, Banich M, Barch D, Bjork JM, Gonzalez MR, Gonzalez R, Haist F, Jacobus J, Lisdahl K, McGlade E, McCandliss B, Nagel B, Nixon SJ, Tapert S, Kennedy JT, Thompson W (2022). Age-related changes and longitudinal stability of individual differences in ABCD Neurocognition measures. Developmental Cognitive Neuroscience. Volume 54, April 2022, 101078

Temporal stability of individual differences is an important prerequisite for accurate tracking of prospective relationships between neurocognition and real-world behavioral outcomes such as substance abuse and psychopathology. Here we report age-related changes and longitudinal test-retest stability (TRS) for the Neurocognition battery of the Adolescent Brain and Cognitive Development (ABCD) study, which included the NIH Toolbox (TB) Cognitive Domain and additional memory and visuospatial processing tests administered at baseline (ages 9–11) and two-year follow-up. As expected, performance improved significantly with age, but the effect size varied broadly, with Pattern Comparison and the Crystallized Cognition Composite showing the largest age-related gain (Cohen’s d:.99 and.97, respectively). TRS ranged from fair (Flanker test: r = 0.44) to excellent (Crystallized Cognition Composite: r = 0.82). A comparison of longitudinal changes and cross-sectional age-related differences within baseline and follow-up assessments suggested that, for some measures, longitudinal changes may be confounded by practice effects and differences in task stimuli or procedure between baseline and follow-up. In conclusion, a subset of measures showed good stability of individual differences despite significant age-related changes, warranting their use as prospective predictors. However, caution is needed in the interpretation of observed longitudinal changes as indicators of neurocognitive development.

The role of school environment in brain structure, connectivity, and mental health in children – a multi-modal investigation

Rakesh D, Zalesky A, Whittle S. The role of school environment in brain structure, connectivity, and mental health in children – a multi-modal investigation. Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Feb 2:S2451-9022(22)00023-4. doi: 10.1016/j.bpsc.2022.01.006. Epub ahead of print. PMID: 35123109.

Background: Much work has been dedicated to understanding the effects of adverse home environments on brain development. While the school social and learning environment plays a role in child development, little work has been done to investigate the impact of the school environment on the developing brain. The goal of the present study was to examine associations between the school environment, brain structure and connectivity, and mental health.

Methods: In this preregistered study we investigated these questions in a large sample of adolescents (9-10 years) from the Adolescent Brain Cognitive Development (ABCD) Study. We examined the association between school environment and gray (N = 10,435). and white matter (N= 10,770) structure and functional connectivity (N = 9,528). We then investigated multivariate relationships between school-associated brain measures and mental health.

Results: School environment was associated with connectivity of the auditory and retrosplenial temporal network as well as of higher-order cognitive networks like the cingulo-opercular, default mode, ventral attention, and frontoparietal networks. Multivariate analyses revealed that connectivity of cingulo-opercular and default mode networks were also associated with mental health.

Conclusions: Findings shed light on the neural mechanisms through which favorable school environments may contribute to positive mental health outcomes in children. Our findings have implications for interventions targeted at promoting positive youth functioning through improving school environments.

Spatio-Temporal Directed Acyclic Graph Learning with Attention Mechanisms on Brain Functional Time Series and Connectivity

Huang S-G, Xia J, Xu L, Qiu A. (2022). Spatio-Temporal Directed Acyclic Graph Learning with Attention Mechanisms on Brain Functional Time Series and Connectivity. Medical Image Analysis, Volume 77, April 2022, 102370.

We develop a deep learning framework, spatio-temporal directed acyclic graph with attention mechanisms (ST-DAG-Att), to predict cognition and disease using functional magnetic resonance imaging (fMRI). This ST-DAG-Att framework comprises of two neural networks, 1) spatio-temporal graph convolutional network (ST-graph-conv) to learn the spatial and temporal information of functional time series at multiple temporal and spatial graph scales, where the graph is represented by the brain functional network, the spatial convolution is over the space of this graph, and the temporal convolution is over the time dimension; 2) functional connectivity convolutional network (FC-conv) to learn functional connectivity features, where the functional connectivity is derived from embedded multi-scale fMRI time series and the convolutional operation is applied along both edge and node dimensions of the brain functional network. This framework also consists of an attention component, i.e., functional connectivity-based spatial attention (FC-SAtt), that generates a spatial attention map through learning the local dependency among high-level features of functional connectivity and emphasizing meaningful brain regions. Moreover, both the ST-graph-conv and FC-conv networks are designed as feed-forward models structured as directed acyclic graphs (DAGs). Our experiments employ two large-scale datasets, Adolescent Brain Cognitive Development (ABCD, n=7693) and Open Access Series of Imaging Study-3 (OASIS-3, n=1786). Our results show that the ST-DAG-Att model is generalizable from cognition prediction to age prediction. It is robust to independent samples obtained from different sites of the ABCD study. It outperforms the existing machine learning techniques, including support vector regression (SVR), elastic net’s mixture with random forest, spatio-temporal graph convolution, and BrainNetCNN.

Erratum to: Morphology of the prefrontal cortex predicts body composition in early adolescence: cognitive mediators and environmental moderators in the ABCD Study

Hall PA, Best JR, Beaton EA, Sakib MN, Danckert J. Erratum to: Morphology of the prefrontal cortex predicts body composition in early adolescence: cognitive mediators and environmental moderators in the ABCD Study. Soc Cogn Affect Neurosci. 2022 Jan 29:nsac002. doi: 10.1093/scan/nsac002. Epub ahead of print. Erratum for: Soc Cogn Affect Neurosci. 2021 Sep 02;: PMID: 35104344.

Associations among Household and Neighborhood Socioeconomic Disadvantages, Resting-state Frontoamygdala Connectivity, and Internalizing Symptoms in Youth

Ip KI, Sisk LM, Horien C, Conley MI, Rapuano KM, Rosenberg MD, Greene AS, Scheinost D, Constable RT, Casey BJ, Baskin-Sommers A, Gee DG. Associations among Household and Neighborhood Socioeconomic Disadvantages, Resting-state Frontoamygdala Connectivity, and Internalizing Symptoms in Youth. J Cogn Neurosci. 2022 Jan 28:1-32. doi: 10.1162/jocn_a_01826. Epub ahead of print. PMID: 35104356.

Exposure to socioeconomic disadvantages (SED) can have negative impacts on mental health, yet SED are a multifaceted construct and the precise processes by which SED confer deleterious effects are less clear. Using a large and diverse sample of preadolescents (ages 9-10 years at baseline, n = 4038, 49% female) from the Adolescent Brain Cognitive Development Study, we examined associations among SED at both household (i.e., income-needs and material hardship) and neighborhood (i.e., area deprivation and neighborhood unsafety) levels, frontoamygdala resting-state functional connectivity, and internalizing symptoms at baseline and 1-year follow-up. SED were positively associated with internalizing symptoms at baseline and indirectly predicted symptoms 1 year later through elevated symptoms at baseline. At the household level, youth in households characterized by higher disadvantage (i.e., lower income-to-needs ratio) exhibited more strongly negative frontoamygdala coupling, particularly between the bilateral amygdala and medial OFC (mOFC) regions within the frontoparietal network. Although more strongly positive amygdala-mOFC coupling was associated with higher levels of internalizing symptoms at baseline and 1-year follow-up, it did not mediate the association between income-to-needs ratio and internalizing symptoms. However, at the neighborhood level, amygdala-mOFC functional coupling moderated the effect of neighborhood deprivation on internalizing symptoms. Specifically, higher neighborhood deprivation was associated with higher internalizing symptoms for youth with more strongly positive connectivity, but not for youth with more strongly negative connectivity, suggesting a potential buffering effect. Findings highlight the importance of capturing multilevel socioecological contexts in which youth develop to identify youth who are most likely to benefit from early interventions.

Birth Weight and Childhood Psychopathology in the ABCD Cohort: Association is Strongest for Attention Problems and is Moderated by Sex

Dooley N, Clarke M, Cotter D, Cannon M. Birth Weight and Childhood Psychopathology in the ABCD Cohort: Association is Strongest for Attention Problems and is Moderated by Sex. Res Child Adolesc Psychopathol. 2022 Jan 24. doi: 10.1007/s10802-021-00859-0. Epub ahead of print. PMID: 35072847.

Many studies have shown low birth weight is associated with psychopathology later in life, particularly attention-deficit/hyperactivity disorder (ADHD). The association is well-replicated, independent from a variety of potential familial confounds, and follows a dose-response curve (decreasing birth weight linked with increasing odds of disorder). However, the specificity of the association to attention problems is called into question by the extent of comorbidity in ADHD, and recent findings that the association is stronger for autism than ADHD. We test the relative dose-response strength of birth weight on multiple aspects of behavior to explore specificity of the effect to attention problems. We also test recent suggestions that the association between birth weight and attention problems is driven by males. Our sample consisted of 9,076 children aged 9-10 from the United States (Adolescent Brain Cognitive Development study). Outcomes included 9 problem-scales and the total problems scale from the Child Behavior Checklist (CBCL). Attention problems were the most strongly associated with birth weight after controlling for gestational age, potential familial confounds, and multiple testing, supporting the outcome-specificity of this association. Contrary to recent registry-based findings, an association between birth weight and an autism scale was not observed. Sex moderated the effect of birth weight on total problems, attention problems and aggressive behavior such that these inverse associations were strongly driven by males. Our findings have strong implications for sex-specific prediction and etiological models of childhood psychopathology.

Socioeconomic status, BMI, and brain development in children

Dennis E, Manza P, Volkow ND. Socioeconomic status, BMI, and brain development in children. Transl Psychiatry. 2022 Jan 24;12(1):33. doi: 10.1038/s41398-022-01779-3. PMID: 35075111.

Low socioeconomic status (SES) in childhood is associated with deficits in executive function and changes in cortical morphology. Furthermore, rates of childhood obesity are greater among low SES children and childhood obesity is also associated with cortical alterations and impaired neurocognition, specifically in the domain of executive function. To investigate the influence of BMI on the relationships between SES and both neurocognition and brain morphology, we used data from the Adolescent Brain Cognitive Development (ABCD) study to construct multiple linear regression models and conduct mediation analyses. Overall, SES as measured by household income, highest level of parental education, and area deprivation, was associated with lower BMI, greater total and prefrontal cortical volume, and better performance on assessments of executive function. Mediation analysis indicated that BMI had a significant indirect effect on associations between area deprivation and both total and prefrontal cortical volumes. BMI also played a mediating role in the associations between area deprivation and composite neurocognitive scores, which were driven by performance on tasks of working memory and cognitive flexibility, but not cognitive control. These findings suggest that BMI should be considered in future studies investigating the relationship between low SES and poor neurodevelopmental outcomes.

Stability of polygenic scores across discovery genome-wide association studies

Schultz LM, Merikangas AK, Ruparel K, Jacquemont S, Glahn DC, Gur RE, Barzilay R, Almasy L. Stability of polygenic scores across discovery genome-wide association studies. HGG Adv. 2022 Jan 21;3(2):100091. doi: 10.1016/j.xhgg.2022.100091. PMID: 35199043; PMCID: PMC8841810.

Polygenic scores (PGS) are commonly evaluated in terms of their predictive accuracy at the population level by the proportion of phenotypic variance they explain. To be useful for precision medicine applications, they also need to be evaluated at the individual level when phenotypes are not necessarily already known. We investigated the stability of PGS in European American (EUR) and African American (AFR)-ancestry individuals from the Philadelphia Neurodevelopmental Cohort and the Adolescent Brain Cognitive Development study using different discovery genome-wide association study (GWAS) results for post-traumatic stress disorder (PTSD), type 2 diabetes (T2D), and height. We found that pairs of EUR-ancestry GWAS for the same trait had genetic correlations >0.92. However, PGS calculated from pairs of same-ancestry and different-ancestry GWAS had correlations that ranged from <0.01 to 0.74. PGS stability was greater for height than for PTSD or T2D. A series of height GWAS in the UK Biobank suggested that correlation between PGS is strongly dependent on the extent of sample overlap between the discovery GWAS. Focusing on the upper end of the PGS distribution, different discovery GWAS do not consistently identify the same individuals in the upper quantiles, with the best case being 60% of individuals above the 80th percentile of PGS overlapping from one height GWAS to another. The degree of overlap decreases sharply as higher quantiles, less heritable traits, and different-ancestry GWAS are considered. PGS computed from different discovery GWAS have only modest correlation at the individual level, underscoring the need to proceed cautiously with integrating PGS into precision medicine applications.

Psychiatric comorbidity associated with weight status in 9 to 10 year old children

Smith KE, Mason TB. Psychiatric comorbidity associated with weight status in 9 to 10 year old children. Pediatr Obes. 2022 Jan 19:e12883. doi: 10.1111/ijpo.12883. Epub ahead of print. PMID: 35048539.

Background: Paediatric overweight and obesity (OW/OB) constitute a serious public health concern. Given that psychological problems may be key contributors to the onset and maintenance of paediatric obesity, the present study examined past and current psychiatric comorbidities across the weight spectrum during middle childhood among a nationally representative sample.

Methods: Participants were 11 708 9- to 10-year-old children (31.6% with OW/OB) and their caregivers who participated in the first wave of data collection in the Adolescent Brain Cognitive Development (ABCD) study. Logistic regressions were used to examine the association between weight status (i.e., underweight, healthy weight, OW, OB) and likelihood of current/past psychiatric diagnoses.

Results: Compared to healthy weight children, those with OW/OB were more likely to have current/past major depressive disorder and binge eating disorder. Relative to healthy weight children, those with OB were more likely to have prior separation anxiety disorder, current specific phobia and oppositional defiant disorder; those with OW were more likely to have PTSD; and those with underweight were more likely to have ADHD.

Conclusions: Results suggest cross-sectional associations among negative emotionality, binge eating, and OW/OB, and highlight the need for ongoing prospective research to investigate directionality of associations and mechanisms of effects.

Transforming the Future of Adolescent Health: Opportunities From the Adolescent Brain Cognitive Development Study

Hoffman EA, LeBlanc K, Weiss SRB, Dowling GJ. Transforming the Future of Adolescent Health: Opportunities From the Adolescent Brain Cognitive Development Study. Journal of Adolescent Health, Vol 70, Issue 2, P186-188, February 01, 2022, DOI:https://doi.org/10.1016/j.jadohealth.2021.11.008

Adolescence is a period of dramatic expansion of the knowledge and skills critical for transitioning into adulthood. Yet, there is much to learn about how adolescent experiences affect brain, cognitive, social, and emotional development. Over the last decade, evidence has revealed associations between early life adversity (e.g., poverty) and later changes in brain structure and function. More recently, research has shown that positive factors (e.g., perceived social supports, increased access to community resources) are associated with healthier development, even for children living in deep poverty, suggesting that protective factors may mitigate the possible negative influences of adverse experiences on health and development . Looking into the next decade, important forces (e.g., digital media, racial inequities, climate change, long-term impacts of COVID-19) will affect adolescent health and well-being globally. Our imperative is to harness advances in science and technology to develop strategies that will enhance health and promote equity.

Conclusion: The diversity of the ABCD cohort, the breadth of data collected, and the longitudinal design of ABCD will provide opportunities for investigating the interplay of environments and experiences with long-term health outcomes. These data have the potential to facilitate the development of strategies for enhancing adolescent health and equity for generations to come.

Motor abnormalities, depression risk, and clinical course in adolescence

Damme KSF, Park JS, Vargas T, Walther S, Shankman SA, Mittal VA. Motor abnormalities, depression risk, and clinical course in adolescence, Biological Psychiatry Global Open Science, Volume 2, Issue 1, January 2022, Pages 61-69, ISSN 2667-1743, https://doi.org/10.1016/j.bpsgos.2021.06.011.

Background
Motor abnormalities, such as psychomotor agitation and retardation, are widely recognized as core features of depression. However, it is not currently known if motor abnormalities connote risk for depression.

Methods
Using data from the Adolescent Brain Cognitive Development (ABCD) Study, a nationally representative sample of youth (n=10,835, 9–11 years old), the present paper examines whether motor abnormalities are associated with (a) depression symptoms in early adolescence, (b) familial risk for depression (familial risk loading), and (c) future depression symptoms. Motor abnormalities measures included traditional (DSM) motor signs such as psychomotor agitation and retardation as well as other motor domains such as developmental motor delays and dyscoordination.

Results
Traditional motor abnormalities were less prevalent (agitation=3.2%, retardation=0.3%) than non-traditional domains (delays=13.79%, coordination=35.5%) among adolescents. Motor dysfunction was associated with depression symptoms (Cohen’s ds=0.02 to 0.12). Familial risk for depression was related to motor abnormalities (Cohen’s ds=0.08 to 0.27), with the exception of motor retardation. Family vulnerability varied in sensitivity to depression risk (e.g., retardation: .53%; dyscoordination: 32.05%). Baseline endorsement of motor abnormalities predicted future depression symptoms at one-year follow-up.

Conclusions
These findings suggest that motor signs reflect a novel, promising future direction for examining vulnerability to depression risk in early adolescence.

Functional connectome mediates the association between sleep disturbance and mental health in preadolescence: A longitudinal mediation study

Yang FN, Liu TT, Wang Z. Functional connectome mediates the association between sleep disturbance and mental health in preadolescence: A longitudinal mediation study. Hum Brain Mapp. 2022 Jan 18. doi: 10.1002/hbm.25772. Epub ahead of print. PMID: 35040524.

Sleep disturbance is known to be associated with various mental disorders and often precedes the onset of mental disorders in youth. Given the increasingly acknowledged bidirectional influence between sleep disturbance and mental disorders, we aim to identify a shared neural mechanism that underlies sleep disturbance and mental disorders in preadolescents. We analyzed a dataset of 9,350 9-10 year-old children, among whom 8,845 had 1-year follow-up data, from the Adolescent Brain Cognitive Development (ABCD) study. Linear mixed-effects models, mediation analysis, and longitudinal mediation analysis were used to investigate the relationship between sleep disturbance, mental disorders, and resting-state network connectivity. Out of 186 unique connectivities, the effect of total sleep disturbance (TSP, from Sleep Disturbance Scale) and mental problems (MP, from Child Behavior Checklist) converged in the default mode network (DMN) and the dorsal attention network (DAN). Within- and between-network connectivities (DMN-DAN, DMN-DMN, DAN-DAN) mediated the relationship between baseline TSD and MP at 1-year follow-up and the relationship between baseline MP and TSD at 1-year follow-up. The pathway model in which sleep disturbance and mental problems affect each other through two anticorrelated brain networks (DMN and DAN) suggests a common neural mechanism between them. Longitudinally, a less segregated DMN and DAN is associated with negative outcomes on mental well-being and sleep disturbance a year later. These findings have important implications for the design of prevention and neurofeedback intervention for mental disorders and sleep problems.

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

Hernandez LM, Kim M, Hernandez C, Thompson W, Fan CC, Galván A, Dapretto M, Bookheimer SY, Fuligni A, Gandal M (In Press, 2022). Decoupling sleep and brain size in childhood: An investigation of genetic covariation in the Adolescent Brain Cognitive Development Study®. Biological Psychiatry, January 17, 2022, DOI:https://doi.org/10.1016/j.bpsgos.2021.12.011

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

Methods
Using data from the Adolescent Brain and Cognitive Development Study (NPhenotype=4,428 for discovery/replication, NGenetics=4,728, age: 9-10), we assessed phenotypic relationships, heritability, and genetic correlation between childhood sleep disturbances (SDs: insomnia, arousal, breathing, somnolence, hyperhidrosis, sleep-wake transitions), brain size (surface area [SA], cortical thickness, volume), and dimensional psychopathology.

Results
SDs showed widespread positive associations with multiple domains of childhood psychopathology; however, only insomnia showed replicable associations with smaller brain SA. Among the SDs assessed, only insomnia showed significant SNP-based heritability (h2SNP=0.15, p<0.05), and showed substantial genetic correlations with externalizing and attention-deficit hyperactivity disorder (ADHD) symptomatology (rG’s>0.80, p’s<0.05). We find no evidence of genetic correlation between childhood insomnia and brain size. Furthermore, polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of adult insomnia and adult brain size did not predict childhood insomnia; instead, PRS trained using ADHD GWAS predicted decreased SA at baseline, as well as insomnia and externalizing symptoms longitudinally.

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

Associations between cognition and polygenic liability to substance involvement in middle childhood: Results from the ABCD study

Paul SE, Hatoum AS, Barch DM, Thompson WK, Agrawal A, Bogdan R, Johnson EC (2022). Associations between cognition and polygenic liability to substance involvement in middle childhood: Results from the ABCD study. Drug and Alcohol Dependence, Volume 232, 1 March 2022, 109277, https://doi.org/10.1016/j.drugalcdep.2022.109277.

Background
Cognition is robustly associated with substance involvement. This relationship is attributable to multiple factors, including genetics, though such contributions show inconsistent patterns in the literature. For instance, genome-wide association studies point to potential positive relationships between educational achievement and common substance use but negative relationships with heavy and/or problematic substance use.

Methods
We estimated associations between polygenic risk for substance involvement (i.e., alcohol, tobacco, and cannabis use and problematic use) and cognition subfacets (i.e., general ability, executive function, learning/memory) derived from confirmatory factor analysis among 3205 substance naïve children (ages 9–10) of European ancestry who completed the baseline session of the Adolescent Brain Cognitive Development (ABCD) Study.

Findings
Polygenic risk for lifetime cannabis use was positively associated with all three facets of cognitive ability (Bs ≥ 0.045, qs ≤ 0.044). No other substance polygenic risk scores showed significant associations with cognition after adjustment for multiple testing (|Bs|≤0.033, qs ≥ 0.118).

Conclusions
Polygenic liability to lifetime cannabis use, but not use disorder, was positively associated with cognitive performance among substance-naïve children, possibly reflecting shared genetic overlap with openness to experience or the influence of genetic variance associated with socioeconomic status. Our lack of findings for the other polygenic scores may reflect ascertainment differences between the genome-wide association study (GWAS) samples and the current sample and/or the young age of the present sample. As longitudinal data in ABCD are collected, this sample may be useful for disentangling putatively causal or predispositional influences of substance use and misuse on cognition.

The ABCD Study: Brain Heterogeneity in Intelligence During a Neurodevelopmental Transition Stage

Zhao Q, Voon V, Zhang L, Shen C, Zhang J, Feng J. The ABCD Study: Brain Heterogeneity in Intelligence During a Neurodevelopmental Transition Stage. Cereb Cortex. 2022 Jan 15:bhab403. doi: 10.1093/cercor/bhab403. Epub ahead of print. PMID: 35037940.

A complex curvilinear relationship exists between intelligence and age during the neurodevelopment of cortical thickness. To parse out a more fine-grained relationship between intelligence and cortical thickness and surface area, we used a large-scale data set focusing on a critical transition juncture in neurodevelopment in preadolescence. Cortical thickness was derived from T1-weighted structural magnetic resonance images of a large sample of 9- and 11-year-old children from the Adolescent Brain Cognitive Development study. The NIH Toolbox Cognition Battery composite scores, which included fluid, crystallized, and total scores, were used to assess intelligence. Using a double generalized linear model, we assessed the independent association between the mean and dispersion of cortical thickness/surface area and intelligence. Higher intelligence in preadolescents was associated with higher mean cortical thickness in orbitofrontal and primary sensory cortices but with lower thickness in the dorsolateral and medial prefrontal cortex and particularly in the rostral anterior cingulate. The rostral anterior cingulate findings were particularly evident across all subscales of intelligence. Higher intelligence was also associated with greater interindividual similarity in the rostral cingulate. Intelligence during this key transition juncture in preadolescence appears to reflect a dissociation between the cortical development of basic cognitive processes and higher-order executive and motivational processes.

General Psychopathology, Cognition, and the Cerebral Cortex in 10-Year-Old Children: Insights From the Adolescent Brain Cognitive Development Study

Patel Y, Parker N, Salum GA, Pausova Z, Paus T. General Psychopathology, Cognition, and the Cerebral Cortex in 10-Year-Old Children: Insights From the Adolescent Brain Cognitive Development Study. Front Hum Neurosci. 2022 Jan 13;15:781554. doi: 10.3389/fnhum.2021.781554. PMID: 35145385; PMCID: PMC8823367.

General psychopathology and cognition are likely to have a bidirectional influence on each other. Yet, the relationship between brain structure, psychopathology, and cognition remains unclear. This brief report investigates the association between structural properties of the cerebral cortex [surface area, cortical thickness, intracortical myelination indexed by the T1w/T2w ratio, and neurite density assessed by restriction spectrum imaging (RSI)] with general psychopathology and cognition in a sample of children from the Adolescent Brain Cognitive Development (ABCD) study. Higher levels of psychopathology and lower levels of cognitive ability were associated with a smaller cortical surface area. Inter-regionally-across the cerebral cortex-the strength of association between an area and psychopathology is strongly correlated with the strength of association between an area and cognition. Taken together, structural deviations particularly observed in the cortical surface area influence both psychopathology and cognition.

Corrigendum to «Microstructural development from 9 to 14 years: Evidence from the ABCD Study»

Palmer CE, Pecheva D, Iversen JR, Hagler DJ Jr, Sugrue L, Nedelec P, Fan CC, Thompson WK, Jernigan TL, Dale AM. Corrigendum to «Microstructural development from 9 to 14 years: Evidence from the ABCD Study» [Dev. Cognit. Neurosci. 53 (2022) 101044]. Dev Cogn Neurosci. 2022 Jan 13:101063. doi: 10.1016/j.dcn.2022.101063. Epub ahead of print. Erratum for: Dev Cogn Neurosci. 2021 Dec 3;53:101044. PMID: 35034850.

Parental psychological problems were associated with higher screen time and the use of mature-rated media in children

Pulkki-Raback L, Barnes JD, Elovainio M, Hakulinen C, Sourander A, Tremblay MS, Guerrero MD. Parental psychological problems were associated with higher screen time and the use of mature-rated media in children. Acta Paediatr. 2022 Jan 12. doi: 10.1111/apa.16253. Epub ahead of print. PMID: 35023210.

Aim: Parents’ psychological problems may affect children’s screen time, but research has been scarce. We examined the association between parental psychological problems and children’s screen media behaviours in a nationally representative sample.

Methods: The participants were from the Adolescent Brain Cognitive Development study, recruited by probability sampling from the USA population. Children reported their use of TV, videos, video games, social media, and mature-rated media. The parents (85% mothers) reported psychological problems using the Adult Self-Report questionnaire.

Results: In 10,650 children (5,112 girls, 5,538 boys) aged 9.9±0.6 years, presence of parental psychological problems was associated with children spending more daily time on screen media and with meeting the recommendation of ≤2 daily hours less often than children whose parents did not have psychological problems. Parental psychological problems were associated with children’s TV watching, video watching and gaming but not with using social media. Parental internalising problems were associated with children watching mature-rated movies (odds ratio [OR] =1.14, 95% confidence interval [CI]=1.00, 1.30) and playing mature-rated games (OR=1.27, 95% CI=1.11, 1.45).

Conclusion: Presence of parental psychological problems is associated with higher screen time and use of mature-rated media in children. This cross-sectional study was not able to examine causal associations.

Moderate-to-vigorous intensity physical activity among adolescents in the USA during the COVID-19 pandemic

Nagata JM, Cortez CA, Dooley EE, Iyer P, Ganson KT, Gabriel KP (2022). Moderate-to-vigorous intensity physical activity among adolescents in the USA during the COVID-19 pandemic. Preventive Medicine Reports, Volume 25, February 2022, 101685. https://doi.org/10.1016/j.pmedr.2021.101685

This study aimed to evaluate adolescents’ moderate-to-vigorous intensity physical activity (MVPA) during the COVID-19 pandemic with regards to sociodemographic characteristics and determine mental health and resiliency factors associated with MVPA among a diverse national sample of adolescents ages 10–14 years. Data were collected during the pandemic in May 2020 from the Adolescent Brain Cognitive Development Study (ABCD, N = 5,153), a national prospective cohort study in the U.S. MVPA was quantified as the product of reported duration and frequency (hours per week), which was further summarized as the proportion meeting age-appropriate 2018 Physical Activity Guidelines for Americans. A similar estimate was generated using MVPA data collected prior to the pandemic. Mental health and resiliency measures were collected during the pandemic. Regression models examined associations between mental health or resiliency measures and MVPA during the pandemic. Median MVPA was 2 h per week (IQR 0, 6). Overall, the percentage of the cohort meeting MVPA guidelines decreased from 16.1% (pre-pandemic) to 8.9% (during the pandemic). Racial/ethnic minority adolescents and adolescents from lower socioeconomic backgrounds were significantly less likely to meet MVPA guidelines during the pandemic. Poorer mental health, COVID-related worry, and stress were associated with lower MVPA, while more social support and coping behaviors were associated with higher MVPA during the pandemic. In this large, national sample of adolescents, the proportion of those meeting MVPA Guidelines was lower during the COVID-19 pandemic, with significant disparities by race/ethnicity and socioeconomic status. Interventions to promote social support and coping behaviors may improve MVPA levels among adolescents during the pandemic.

Measurement of Gender and Sexuality in the Adolescent Brain Cognitive Development (ABCD) Study

Alexandra S. Potter, Sarahjane L. Dube, Lisa C. Barrios, Susan Bookheimer, Abigail Espinoza, Sarah W. Feldstein Ewing, Edward G. Freedman, Elizabeth A. Hoffman, Masha Ivanova, Hailee Jefferys, Erin C. McGlade, Susan F. Tapert, Michelle M Johns (2022). Measurement of Gender and Sexuality in the Adolescent Brain Cognitive Development (ABCD) Study, Developmental Cognitive Neuroscience, Volume 53, February 2022, 101057, ISSN 1878-9293, https://doi.org/10.1016/j.dcn.2022.101057.

The Adolescent Brain Cognitive DevelopmentSM (ABCD) study is a longitudinal study of adolescent brain development and health that includes over 11,800 youth in the United States. The ABCD study includes broad developmental domains, and gender and sexuality are two of these with noted changes across late childhood and early adolescence. The Gender Identity and Sexual Health (GISH) workgroup recommends measures of gender and sexuality for the ABCD study, prioritizing those that are developmentally sensitive, capture individual differences in the experience of gender and sexuality, and minimize participant burden. This manuscript describes the gender and sexuality measures used in ABCD and provides guidance for researchers using these data. Data showing the utility of these measures and longitudinal trends are presented. Including assessment of gender and sexuality in ABCD allows for characterization of developmental trajectories of gender and sexuality, and the broad scope of ABCD data collection allows examination of identity development in an intersectional manner.

Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample

Wang B, Giannakopoulou O, Austin-Zimmerman I, Irizar H, Harju-Seppänen J, Zartaloudi E, Bhat A, McQuillin A, Kuchenbäcker K, Bramon E. Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample. Genes (Basel). 2022 Jan 3;13(1):106. doi: 10.3390/genes13010106. PMID: 35052446.

Verbal memory impairment is one of the most prominent cognitive deficits in psychosis. However, few studies have investigated the genetic basis of verbal memory in a neurodevelopmental context, and most genome-wide association studies (GWASs) have been conducted in European-ancestry populations. We conducted a GWAS on verbal memory in a maximum of 11,017 participants aged 8.9 to 11.1 years in the Adolescent Brain Cognitive Development Study®, recruited from a diverse population in the United States. Verbal memory was assessed by the Rey Auditory Verbal Learning Test, which included three measures of verbal memory: immediate recall, short-delay recall, and long-delay recall. We adopted a mixed-model approach to perform a joint GWAS of all participants, adjusting for ancestral background and familial relatedness. The inclusion of participants from all ancestries increased the power of the GWAS. Two novel genome-wide significant associations were found for short-delay and long-delay recall verbal memory. In particular, one locus (rs9896243) associated with long-delay recall was mapped to the NSF (N-Ethylmaleimide Sensitive Factor, Vesicle Fusing ATPase) gene, indicating the role of membrane fusion in adolescent verbal memory. Based on the GWAS in the European subset, we estimated the SNP-heritability to be 15% to 29% for the three verbal memory traits. We found that verbal memory was genetically correlated with schizophrenia, providing further evidence supporting verbal memory as an endophenotype for psychosis.

Association of maternal diabetes with offspring childhood hypothalamic gliosis

Olerich, K., Sewaybricker, L., Chandrasekaran, S., Melhorn, S., Kee, S., & Schur, E. A. (2022). Association of maternal diabetes with offspring childhood hypothalamic gliosis. American Journal of Obstetrics & Gynecology, 226(1), S157-S158.

Objective
Maternal diabetes (MDM) during pregnancy affects the future metabolic health of the offspring. One possible mechanism by which MDM could enduringly impact offspring health is via an effect on the fetal brain. Specifically, we hypothesize that in utero exposure to MDM contributes to long-term alterations in offspring brain microstructure, through an inflammatory process called gliosis, within the energy regulatory centers of the mediobasal hypothalamus (MBH). MBH gliosis, quantifiable by MRI, is associated with increased adiposity and insulin resistance in children and adults.

Study Design
This is an ancillary analysis of the Adolescent Brain Cognitive Development study of child brain development and health. Children (9-11y) with brain MRIs and a completed maternal pregnancy survey were included. The presence of MDM, during the child’s gestation, was our exposure. Using MRI analytic software, regions of interest were placed in the MBH and reference brain regions. Evidence of MBH gliosis was based on higher T2-signal ratios in the MBH compared to amygdala (MBH/AMY; outcome). Putamen (PUT)/AMY and MBH/PUT were negative and positive control ratios, respectively. Statistical testing was by linear mixed model, adjusted for child age, sex, ethnicity, BMI and study site.

Results
Our analysis included 273 children: 224 MDM-unexposed and 49 MDM-exposed. MDM-exposed children had higher birth weights, BMI z-scores and waist-height ratios (Table 1). Mean MBH/AMY T2-signal ratios were significantly higher in the MDM-exposed children, compared to unexposed, consistent with MBH gliosis (Fig. 1). A region-ratio*MDM-group interaction was significant (chi2(2): 6.13, p=0.046). Post hoc testing confirmed that mean MBH/AMY T2-signal ratios were significantly higher in the MDM-exposed children, compared to unexposed, as were positive, but not negative, control ratios (Fig 1).

Conclusion
MDM-exposed children display greater evidence of MBH gliosis. The association between MDM and offspring MBH gliosis represents one pathway by which the in utero environment may influence the long-term metabolic health of the offspring.

2021
The Emotional Word-Emotional Face Stroop task in the ABCD study: Psychometric validation and associations with measures of cognition and psychopathology

Smolker HR, Wang K, Luciana M, Bjork JM, Gonzalez R, Barch DM, McGlade EC, Kaiser RH, Friedman NP, Hewitt JK, Banich MT. The Emotional Word-Emotional Face Stroop task in the ABCD study: Psychometric validation and associations with measures of cognition and psychopathology. Dev Cogn Neurosci. 2021 Dec 21;53:101054. doi: 10.1016/j.dcn.2021.101054. Epub ahead of print. PMID: 34954668.

Characterizing the interactions among attention, cognitive control, and emotion during adolescence may provide important insights into why this critical developmental period coincides with a dramatic increase in risk for psychopathology. However, it has proven challenging to develop a single neurobehavioral task that simultaneously engages and differentially measures these diverse domains. In the current study, we describe properties of performance on the Emotional Word-Emotional Face Stroop (EWEFS) task in the Adolescent Brain Cognitive Development (ABCD) Study, a task that allows researchers to concurrently measure processing speed/attentional vigilance (i.e., performance on congruent trials), inhibitory control (i.e., Stroop interference effect), and emotional information processing (i.e., difference in performance on trials with happy as compared to angry distracting faces). We first demonstrate that the task manipulations worked as designed and that Stroop performance is associated with multiple cognitive constructs derived from different measures at a prior time point. We then show that Stroop metrics tapping these three domains are preferentially associated with aspects of externalizing psychopathology and inattention. These results highlight the potential of the EWEFS task to help elucidate the longitudinal dynamics of attention, inhibitory control, and emotion across adolescent development, dynamics which may be altered by level of psychopathology.

Impact of COVID-19 on Youth With ADHD: Predictors and Moderators of Response to Pandemic Restrictions on Daily Life

Rosenthal E, Franklin-Gillette S, Jung HJ, Nelson A, Evans SW, Power TJ, Yerys BE, Dever BV, Reckner E, DuPaul GJ. Impact of COVID-19 on Youth With ADHD: Predictors and Moderators of Response to Pandemic Restrictions on Daily Life. J Atten Disord. 2021 Dec 17:10870547211063641. doi: 10.1177/10870547211063641. Epub ahead of print. PMID: 34920689.

We examined COVID-19 symptoms and infection rates, disruptions to functioning, and moderators of pandemic response for 620 youth with ADHD and 614 individually matched controls (70% male; Mage = 12.4) participating in the Adolescent Brain and Cognitive Development study. There were no group differences in COVID-19 infection rate; however, youth with ADHD were more likely to exhibit COVID-19 symptoms (d = 0.25), greater sleep problems (d = -0.52), fear and negative emotions to infection risk (d = -0.56), trouble with remote learning (d = -0.54), rule-breaking behavior related to COVID-19 restrictions (d = -0.23), family conflict (d = -0.13), and were less prepared for the next school year (d = 0.38). Youth with ADHD were less responsive to protective environmental variables (e.g., parental monitoring, school engagement) during the pandemic and may need more specialized support with return to in-person schooling and daily activities.

One-year predictions of delayed reward discounting in the adolescent brain cognitive development study

Owens, M. M., Hahn, S., Allgaier, N., MacKillop, J., Albaugh, M., Yuan, D., Juliano, A., Potter, A., & Garavan, H. (2021). One-year predictions of delayed reward discounting in the adolescent brain cognitive development study. Experimental and Clinical Psychopharmacology. Advance online publication. https://doi.org/10.1037/pha0000532

Delayed reward discounting (DRD) refers to the extent to which an individual devalues a reward based on a temporal delay and is known to be elevated in individuals with substance use disorders and many mental illnesses. DRD has been linked previously with both features of brain structure and function, as well as various behavioral, psychological, and life-history factors. However, there has been little work on the neurobiological and behavioral antecedents of DRD in childhood. This is an important question, as understanding the antecedents of DRD can provide signs of mechanisms in the development of psychopathology. The present study used baseline data from the Adolescent Brain Cognitive Development Study (N = 4,042) to build machine learning models to predict DRD at the first follow-up visit, 1 year later. In separate machine learning models, we tested elastic net regression, random forest regression, light gradient boosting regression, and support vector regression. In five-fold cross-validation on the training set, models using an array of questionnaire/task variables were able to predict DRD, with these findings generalizing to a held-out (i.e., “lockbox”) test set of 20% of the sample. Key predictive variables were neuropsychological test performance at baseline, socioeconomic status, screen media activity, psychopathology, parenting, and personality. However, models using magnetic resonance imaging (MRI)-derived brain variables did not reliably predict DRD in either the cross-validation or held-out test set. These results suggest a combination of questionnaire/task variables as antecedents of excessive DRD in late childhood, which may presage the development of problematic substance use in adolescence.

Parent-adolescent discrepancies in adolescent recreational screen time reporting during the COVID-19 pandemic

Nagata JM, Cortez CA, Iyer P, Ganson KT, Chu J, Conroy AA. Parent-adolescent discrepancies in adolescent recreational screen time reporting during the COVID-19 pandemic. Acad Pediatr. 2021 Dec 16:S1876-2859(21)00623-9. doi: 10.1016/j.acap.2021.12.008. Epub ahead of print. PMID: 34923146.

Objective: To describe the relationship between parent and adolescent reports of adolescent recreational screen time and to determine sociodemographic predictors of recreational screen time reporting differences during the COVID-19 pandemic.

Methods: We analyzed data from the Adolescent Brain Cognitive Development Study (ABCD, N=5,335, ages 10-14) a national prospective cohort study in the US collected in May 2020. We compared parent-reported, adolescent-reported, and a parent-adolescent differences in recreational screen time hours per day across five screen categories.

Results: Adolescents’ total recreational screen time per day was reported as 4.46 hours by parents and 3.87 hours by adolescents. Parents reported higher levels of their child’s texting, video chatting, and total recreational screen time, while adolescents reported higher multi-player gaming and social media use. Larger discrepancies in total recreational screen time were found in older, Black, and Latino/Hispanic adolescents. Larger discrepancies in total recreational screen time were also found among unmarried/unpartnered parents.

Conclusions: Given discrepancies in parent-adolescent recreational screen time reporting during the pandemic, a period of high screen use, pediatricians should encourage family discussions about adolescent media use through the development of a Family Media Use Plan. The digital media industry could provide more opportunities for parental monitoring of recreational screen time within product designs.

Longitudinal Impact of Childhood Adversity on Early Adolescent Mental Health During the COVID-19 Pandemic in the ABCD Study® Cohort: Does Race or Ethnicity Moderate Findings?

Stinson EA, Sullivan RM, Peteet BJ, Tapert SF, Baker FC, Breslin FJ, Dick AS, Gonzalez MR, Guillaume M, Marshall AT, McCabe CJ, Pelham WE 3rd, Van Rinsveld AM, Sheth CS, Sowell ER, Wade NE, Wallace AL, Lisdahl KM (2021). Longitudinal Impact of Childhood Adversity on Early Adolescent Mental Health During the COVID-19 Pandemic in the ABCD Study® Cohort: Does Race or Ethnicity Moderate Findings?, Biological Psychiatry Global Open Science, Volume 1, Issue 4, December 2021, Pages 324-335, ISSN 2667-1743. https://doi.org/10.1016/j.bpsgos.2021.08.007.

Background
During the COVID-19 pandemic in the United States, mental health among youth has been negatively affected. Youth with a history of adverse childhood experiences (ACEs), as well as youth from minoritized racial-ethnic backgrounds, may be especially vulnerable to experiencing COVID-19–related distress. The aims of this study are to examine whether exposure to pre-pandemic ACEs predicts mental health during the COVID-19 pandemic in youth and whether racial-ethnic background moderates these effects.

Methods
From May to August 2020, 7983 youths (mean age, 12.5 years; range, 10.6–14.6 years) in the Adolescent Brain Cognitive Development (ABCD) Study completed at least one of three online surveys measuring the impact of the pandemic on their mental health. Data were evaluated in relation to youths’ pre-pandemic mental health and ACEs.

Results
Pre-pandemic ACE history significantly predicted poorer mental health across all outcomes and greater COVID-19–related stress and impact of fears on well-being. Youths reported improved mental health during the pandemic (from May to August 2020). While reporting similar levels of mental health, youths from minoritized racial-ethnic backgrounds had elevated COVID-19–related worry, stress, and impact on well-being. Race and ethnicity generally did not moderate ACE effects. Older youths, girls, and those with greater pre-pandemic internalizing symptoms also reported greater mental health symptoms.

Conclusions
Youths who experienced greater childhood adversity reported greater negative affect and COVID-19–related distress during the pandemic. Although they reported generally better mood, Asian American, Black, and multiracial youths reported greater COVID-19–related distress and experienced COVID-19–related discrimination compared with non-Hispanic White youths, highlighting potential health disparities.

Prevalence, predictors, and treatment of eating disorders in children: A national study

Sanzari, C., Levin, R., & Liu, R. (2021). Prevalence, predictors, and treatment of eating disorders in children: A national study. Psychological Medicine, 1-8. doi:10.1017/S0033291721004992\

Background
Although the prevalence rates of preadolescent eating disorders (EDs) are on the rise, considerably less is known about the correlates and treatment of EDs in this age group. Clarifying the epidemiology of EDs in preadolescent children is a necessary first step to understand the nature and scope of this problem in this age group.

Methods
Analysis of data collected in the ABCD Study release 2.0.1. The ABCD cohort was a population-based sample that consisted of 11 721 children ages 9–10 years. Measures included reports of a lifetime and current mental disorders determined using a diagnostic interview for DSM-5 disorders, sociodemographic factors, and psychiatric treatment utilization.

Results
The lifetime prevalence of EDs was 0.95%. Being Black, multiracial, having unmarried parents, and family economic insecurity were significant predictors for developing an ED. Among psychiatric conditions, the major depressive disorder was most robustly associated with EDs in both cross-sectional and temporal analyses. Only 47.40% of children who had a lifetime ED received some type of psychiatric treatment. EDs were not a significant predictor of psychiatric treatment utilization after accounting for sex, sexual orientation, parent marital status, economic insecurity, and all other psychiatric diagnoses.

Conclusions
Despite increasing prevalence rates of preadolescent EDs, the current findings suggest that the majority of children with these disorders remain untreated. Devoting increased attention and resources to reaching families of children with EDs with the least means for receiving care, and screening for EDs in children with depression, may be important steps for reducing this unmet need.

Brain network coupling associated with cognitive performance varies as a function of a child’s environment in the ABCD study

Ellwood-Lowe, M.E., Whitfield-Gabrieli, S. & Bunge, S.A. Brain network coupling associated with cognitive performance varies as a function of a child’s environment in the ABCD study. Nat Commun 12, 7183 (2021). https://doi.org/10.1038/s41467-021-27336-y

Prior research indicates that lower resting-state functional coupling between two brain networks, lateral frontoparietal network (LFPN) and default mode network (DMN), relates to cognitive test performance, for children and adults. However, most of the research that led to this conclusion has been conducted with non-representative samples of individuals from higher-income backgrounds, and so further studies including participants from a broader range of socioeconomic backgrounds are required. Here, in a pre-registered study, we analyzed resting-state fMRI from 6839 children ages 9–10 years from the ABCD dataset. For children from households defined as being above poverty (family of 4 with income > $25,000, or family of 5+ with income > $35,000), we replicated prior findings; that is, we found that better performance on cognitive tests correlated with weaker LFPN-DMN coupling. For children from households defined as being in poverty, the direction of association was reversed, on average: better performance was instead directionally related to stronger LFPN-DMN connectivity, though there was considerable variability. Among children in households below poverty, the direction of this association was predicted in part by features of their environments, such as school type and parent-reported neighborhood safety. These results highlight the importance of including representative samples in studies of child cognitive development.

Microstructural development from 9 to 14 years: Evidence from the ABCD Study

Clare E. Palmer, Diliana Pecheva, John R. Iversen, Donald J. Hagler, Leo Sugrue, Pierre Nedelec, Chun Chieh Fan, Wesley K. Thompson, Terry L. Jernigan, Anders M. Dale, Microstructural development from 9 to 14 years: Evidence from the ABCD Study, Developmental Cognitive Neuroscience, Volume 53, 2022, 101044, ISSN 1878-9293,https://doi.org/10.1016/j.dcn.2021.101044.

During late childhood behavioral changes, such as increased risk-taking and emotional reactivity, have been associated with the maturation of cortico-cortico and cortico-subcortical circuits. Understanding microstructural changes in both white matter and subcortical regions may aid our understanding of how individual differences in these behaviors emerge. Restriction spectrum imaging (RSI) is a framework for modelling diffusion-weighted imaging that decomposes the diffusion signal from a voxel into hindered, restricted, and free compartments. This yields greater specificity than conventional methods of characterizing diffusion. Using RSI, we quantified voxelwise restricted diffusion across the brain and measured age associations in a large sample (n = 8086) from the Adolescent Brain and Cognitive Development (ABCD) study aged 9–14 years. Older participants showed a higher restricted signal fraction across the brain, with the largest associations in subcortical regions, particularly the basal ganglia and ventral diencephalon. Importantly, age associations varied with respect to the cytoarchitecture within white matter fiber tracts and subcortical structures, for example age associations differed across thalamic nuclei. This suggests that age-related changes may map onto specific cell populations or circuits and highlights the utility of voxelwise compared to ROI-wise analyses. Future analyses will aim to understand the relevance of this microstructural developmental for behavioral outcomes.

Adolescent Brain Cognitive Development (ABCD) study Linked External Data (LED): Protocol and practices for geocoding and assignment of environmental data

Fan CC, Marshall A, Smolker H, Gonzalez MR, Tapert SF, Barch DM, Sowell E, Dowling GJ, Cardenas-Iniguez C, Ross J, Thompson WK, Herting MM. Adolescent Brain Cognitive Development (ABCD) study Linked External Data (LED): Protocol and practices for geocoding and assignment of environmental data. Dev Cogn Neurosci, Volume 52, December 2021, 101030. doi: 10.1016/j.dcn.2021.101030. Epub ahead of print. PMID: 34891080.

Our brain is constantly shaped by our immediate environments, and while some effects are transient, some have long-term consequences. Therefore, it is critical to identify which environmental risks have evident and long-term impact on brain development. To expand our understanding of the environmental context of each child, the Adolescent Brain Cognitive Development (ABCD) Study® incorporates the use of geospatial location data to capture a range of individual, neighborhood, and state level data based on the child’s residential location in order to elucidate the physical environmental contexts in which today’s youth are growing up. We review the major considerations and types of geocoded information incorporated by the Linked External Data Environmental (LED) workgroup to expand on the built and natural environmental constructs in the existing and future ABCD Study data releases. Understanding the environmental context of each youth furthers the consortium’s mission to understand factors that may influence individual differences in brain development, providing the opportunity to inform public policy and health organization guidelines for child and adolescent health.

Measurement matters: An individual differences examination of family socioeconomic factors, latent dimensions of children’s experiences, and resting state functional brain connectivity in the ABCD sample

DeJoseph ML, Herzberg MP, Sifre RD, Berry D, Thomas KM. Measurement matters: An individual differences examination of family socioeconomic factors, latent dimensions of children’s experiences, and resting state functional brain connectivity in the ABCD sample. Dev Cogn Neurosci. 2021 Dec 8;53:101043. doi: 10.1016/j.dcn.2021.101043. Epub ahead of print. PMID: 34915436.

The variation in experiences between high and low-socioeconomic status contexts are posited to play a crucial role in shaping the developing brain and may explain differences in child outcomes. Yet, examinations of SES and brain development have largely been limited to distal proxies of these experiences (e.g., income comparisons). The current study sought to disentangle the effects of multiple socioeconomic indices and dimensions of more proximal experiences on resting-state functional connectivity (rsFC) in a sample of 7834 youth (aged 9-10 years) from the Adolescent Brain Cognitive Development (ABCD) study. We applied moderated nonlinear factor analysis (MNLFA) to establish measurement invariance among three latent environmental dimensions of experience (material/economic deprivation, caregiver social support, and psychosocial threat). Results revealed measurement biases as a function of child age, sex, racial group, family income, and parental education, which were statistically adjusted in the final MNLFA scores. Mixed-effects models demonstrated that socioeconomic indices and psychosocial threat differentially predicted variation in frontolimbic networks, and threat statistically moderated the association between income and connectivity between the dorsal and ventral attention networks. Findings illuminate the importance of reducing measurement biases to gain a more socioculturally-valid understanding of the complex and nuanced links between socioeconomic context, children’s experiences, and neurodevelopment.

Reward Processing in Children With Psychotic-Like Experiences

Harju-Seppänen J, Irizar H, Bramon E, Blakemore SJ, Mason L, Bell V. Reward Processing in Children With Psychotic-Like Experiences. Schizophr Bull Open. 2021 Dec 4;3(1):sgab054. doi: 10.1093/schizbullopen/sgab054. PMID: 35036918; PMCID: PMC8756103.

Alterations to striatal reward pathways have been identified in individuals with psychosis. They are hypothesized to be a key mechanism that generate psychotic symptoms through the production of aberrant attribution of motivational salience and are proposed to result from accumulated childhood adversity and genetic risk, making the striatal system hyper-responsive to stress. However, few studies have examined whether children with psychotic-like experiences (PLEs) also exhibit these alterations, limiting our understanding of how differences in reward processing relate to hallucinations and delusional ideation in childhood. Consequently, we examined whether PLEs and PLE-related distress were associated with reward-related activation in the nucleus accumbens (NAcc). The sample consisted of children (N = 6718) from the Adolescent Brain Cognitive Development (ABCD) study aged 9-10 years who had participated in the Monetary Incentive Delay (MID) task in functional MRI. We used robust mixed-effects linear regression models to investigate the relationship between PLEs and NAcc activation during the reward anticipation and reward outcome stages of the MID task. Analyses were adjusted for gender, household income, ethnicity, depressive symptoms, movement in the scanner, pubertal development, scanner ID, subject and family ID. There was no reliable association between PLEs and alterations to anticipation- or outcome-related striatal reward processing. We discuss the implications for developmental models of psychosis and suggest a developmental delay model of how PLEs may arise at this stage of development.

Associations Between Traumatic Stress, Brain Volumes and Post-traumatic Stress Disorder Symptoms in Children: Data from the ABCD Study

Bustamante D, Amstadter AB, Pritikin JN, Brick TR, Neale MC. Associations Between Traumatic Stress, Brain Volumes and Post-traumatic Stress Disorder Symptoms in Children: Data from the ABCD Study. Behav Genet. 2021 Dec 3. doi: 10.1007/s10519-021-10092-6. Epub ahead of print. PMID: 34860306.

Reduced volumes in brain regions of interest (ROIs), primarily from adult samples, are associated with posttraumatic stress disorder (PTSD). We extended this work to children using data from the Adolescent Brain Cognitive Development (ABCD) Study® (N = 11,848; Mage = 9.92). Structural equation modeling and an elastic-net (EN) machine-learning approach were used to identify potential effects of traumatic events (TEs) on PTSD symptoms (PTSDsx) directly, and indirectly via the volumes 300 subcortical and cortical ROIs. We then estimated the genetic and environmental variation in the phenotypes. TEs were directly associated with PTSDsx (r = 0.92) in children, but their indirect effects (r < 0.0004)-via the volumes of EN-identified subcortical and cortical ROIs-were negligible at this age. Additive genetic factors explained a modest proportion of the variance in TEs (23.4%) and PTSDsx (21.3%), and accounted for most of the variance of EN-identified volumes of four of the five subcortical (52.4-61.8%) three of the nine cortical ROIs (46.4-53.3%) and cerebral white matter in the left hemisphere (57.4%). Environmental factors explained most of the variance in TEs (C = 61.6%, E = 15.1%), PTSDsx (residual-C = 18.4%, residual-E = 21.8%), right lateral ventricle (C = 15.2%, E = 43.1%) and six of the nine EN-identified cortical ROIs (C = 4.0-13.6%, E = 56.7-74.8%). There is negligible evidence that the volumes of brain ROIs are associated with the indirect effects of TEs on PTSDsx at this age. Overall, environmental factors accounted for more of the variation in TEs and PTSDsx. Whereas additive genetic factors accounted for most of the variability in the volumes of a minority of cortical and in most of subcortical ROIs.

Psychotic-like experiences associated with sleep disturbance and brain volumes in youth: Findings from the adolescent brain cognitive development study

Lunsford-Avery JR, Damme KSF, Vargas T, Sweitzer MM, Mittal VA. Psychotic-like experiences associated with sleep disturbance and brain volumes in youth: Findings from the adolescent brain cognitive development study. Association for Child and Adolescent Mental Health. Dec. 2, 2021. https://doi.org/10.1002/jcv2.12055.

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

Methods
Brain volumes of five sleep-related structures were examined in relation to PLEs and difficulties initiating and maintaining sleep (DIMS) in 9,260 9- to 11-year-olds participating in the Adolescent Brain Cognitive Development (ABCD) study. Analytic models examined relationships between DIMS, PLEs, and brain volumes, as well as DIMS as a mediator of brain volume–PLEs relationships. Although sleep regulation structures (i.e., thalamus, basal forebrain, and hypothalamus) were of primary interest, other potentially relevant structures to sleep-related functioning and psychosis (i.e., hippocampus and amygdala) were also examined.

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

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

Association of Outdoor Ambient Fine Particulate Matter With Intracellular White Matter Microstructural Properties Among Children

Burnor E, Cserbik D, Cotter DL, Palmer CE, Ahmadi H, Eckel SP, Berhane K, McConnell R, Chen JC, Schwartz J, Jackson R, Herting MM. Association of Outdoor Ambient Fine Particulate Matter With Intracellular White Matter Microstructural Properties Among Children. JAMA Netw Open. 2021 Dec 1;4(12):e2138300. doi: 10.1001/jamanetworkopen.2021.38300. PMID: 34882178.

Importance: Outdoor particulate matter 2.5 μm or less in diameter (PM2.5) is a ubiquitous environmental neurotoxicant that may affect the developing brain. Little is known about associations between PM2.5 and white matter connectivity.

Objectives: To assess associations between annual residential PM2.5 exposure and white matter microstructure health in a US sample of children 9 to 10 years of age and to examine whether associations are specific to certain white matter pathways or vary across neuroimaging diffusion markers reflective of intracellular and extracellular microstructural processes.

Design, setting, and participants: This cross-sectional study, the Adolescent Brain and Cognitive Development (ABCD) Study, was composed of 21 study sites across the US and used baseline data collected from children 9 to 10 years of age from September 1, 2016, to October 15, 2018. Data analysis was performed from September 15, 2020, to June 30, 2021.

Exposures: Annual mean PM2.5 exposure estimated by ensemble-based models and assigned to the primary residential addresses at baseline.

Main outcomes and measures: Diffusion-weighted imaging (DWI) and tractography were used to delineate white matter tracts. The biophysical modeling technique of restriction spectrum imaging (RSI) was implemented to examine total hindered diffusion and restricted isotropic and anisotropic intracellular diffusion in each tract. Hierarchical mixed-effects models with natural splines were used to analyze the associations between PM2.5 exposure and DWI.

Results: In a study population of 7602 children (mean [SD] age, 119.1 [7.42] months; 3955 [52.0%] female; 160 [ 21.%] Asian, 1025 [13.5%] Black, 1616 [21.3%] Hispanic, 4025 [52.9%] White, and 774 [10.2%] other [identified by parents as American Indian/Native American or Alaska Native; Native Hawaiian, Guamanian, Samoan, other Pacific Islander; Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, or other Asian; or other race]), associations were seen between annual ambient PM2.5 and hemispheric differences in white matter microstructure. Hemisphere-stratified models revealed significant associations between PM2.5 exposure and restricted isotropic intracellular diffusion in the left cingulum, in the left superior longitudinal fasciculus, and bilaterally in the fornix and uncinate fasciculus. In tracts with strong positive associations, a PM2.5 increase from 8 to 12 μg/m3 was associated with increases of 2.16% (95% CI, 0.49%-3.84%) in the left cingulum, 1.95% (95% CI, 0.43%-3.47%) in the left uncinate, and 1.68% (95% CI, 0.01%-3.34%) in the right uncinate. Widespread negative associations were observed between PM2.5 and mean diffusivity.

Conclusions and relevance: The findings of this cross-sectional study suggest that annual mean PM2.5 exposure during childhood is associated with increased restricted isotropic diffusion and decreased mean diffusivity of specific white matter tracts, potentially reflecting differences in the composition of white matter microarchitecture.

Racism-Related Diminished Returns of Socioeconomic Status on Adolescent Brain and Cognitive Development

Boyce S, Darvishi M, Marandi R, Rahmanian R, Akhtar S, Patterson J, Assari S. Racism-Related Diminished Returns of Socioeconomic Status on Adolescent Brain and Cognitive Development. Research in Health Science, 6(4):p1, December 2021, DOI:10.22158/rhs.v6n4p1

Socioeconomic status (SES) influences health, behaviors, and well-being. Emerging information suggests that SES effects on health may be in part be due to SES effects on brain development. We have conducted a mini review of U.S.-based studies examining SES effects on brain development to synthesize the existing knowledge on what brain structures and functions show large and consistent SES influences. We have reviewed SES effects on performance in various cognitive functions such as learning, memory, and language. Additionally, we have reviewed the emerging literature from the Adolescent Brain Cognitive Development (ABCD) study on the effects of social marginalization in reducing the effects of SES on children and youth brain development. These diminished returns of SES in minoritized youth are not due to genetics; rather, we argue that they stem from systemic and structural racism, social stratification, and marginalization that generate inequalities across the SES spectrum. As a result of these diminished returns, inequalities expand from low-SES to mid- and high SES sections of US society.

Predicting multilingual effects on executive function and individual connectomes in children: An ABCD study

Kwon YH, Yoo K, Nguyen H, Jeong Y, Chun MM. Predicting multilingual effects on executive function and individual connectomes in children: An ABCD study. Proc Natl Acad Sci U S A. 2021 Dec 7;118(49):e2110811118. doi: 10.1073/pnas.2110811118. PMID: 34845019.

While there is a substantial amount of work studying multilingualism’s effect on cognitive functions, little is known about how the multilingual experience modulates the brain as a whole. In this study, we analyzed data of over 1,000 children from the Adolescent Brain Cognitive Development (ABCD) Study to examine whether monolinguals and multilinguals differ in executive function, functional brain connectivity, and brain-behavior associations. We observed significantly better performance from multilingual children than monolinguals in working-memory tasks. In one finding, we were able to classify multilinguals from monolinguals using only their whole-brain functional connectome at rest and during an emotional n-back task. Compared to monolinguals, the multilingual group had different functional connectivity mainly in the occipital lobe and subcortical areas during the emotional n-back task and in the occipital lobe and prefrontal cortex at rest. In contrast, we did not find any differences in behavioral performance and functional connectivity when performing a stop-signal task. As a second finding, we investigated the degree to which behavior is reflected in the brain by implementing a connectome-based behavior prediction approach. The multilingual group showed a significant correlation between observed and connectome-predicted individual working-memory performance scores, while the monolingual group did not show any correlations. Overall, our observations suggest that multilingualism enhances executive function and reliably modulates the corresponding brain functional connectome, distinguishing multilinguals from monolinguals even at the developmental stage.

Big Data-Driven Brain Parcellation from fMRI: Impact of Cohort Heterogeneity on Functional Connectivity Maps

Brooks SJ, Parks SM, Stamoulis C. Big Data-Driven Brain Parcellation from fMRI: Impact of Cohort Heterogeneity on Functional Connectivity Maps. Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021:3133-3136. doi: 10.1109/EMBC46164.2021.9630267. PMID: 34891905.

Ongoing large-scale human brain studies are generating complex neuroimaging data from thousands of individuals that can be leveraged to derive data-driven, anatomically accurate brain parcellations. However, despite their promise and many strengths, these data are highly heterogeneous, a characteristic that may affect the anatomical accuracy and generalization of the template but has received relatively little attention. Using multiple similarity measures and thresholding approaches, this study investigated the topological intra- and inter-individual variability of restingstate (rs) functional edge maps (often used for brain parcellation), estimated from rs-fMRI connectivity in n = 5878 children from the Adolescent Brain Cognitive Development (ABCD) study. Findings from this initial investigation indicate that choosing a subject- vs cohort-based threshold for estimating edge maps from connectivity matrices does not significantly impact the map topology. In contrast, the choice of similarity measure and non-linear relationship between similarity and edge map sparsity may have a significant impact on map classification and the generation of parcellation atlases. Multi-level classification revealed multiple clusters with a potentially complex mapping onto biological variables beyond simple demographics.Clinical Relevance- Case-control neuroimaging studies should use domain-specific (e.g., demographics-specific) atlases for parcellating the brain, to improve accuracy and rigor of cohort comparisons. To be generalizable, such atlases need to be derived from large datasets, which are inherently heterogeneous. In a cohort of 5878 children (age ~9-10 years), this study systematically assessed the impact of heterogeneity and similarity of edge maps, which are derived from rs-fMRI connectivity and typically used to generate parcellation atlases.

Multimodal ensemble deep learning to predict disruptive behavior disorders in children

Menon, S. S., & Krishnamurthy, K. (2021). Multimodal ensemble deep learning to predict disruptive behavior disorders in children. Frontiers in Neuroinformatics, doi:http://dx.doi.org/10.3389/fninf.2021.742807

Oppositional defiant disorder and conduct disorder, collectively referred to as disruptive behavior disorders (DBDs), are prevalent psychiatric disorders in children. Early diagnosis of DBDs is crucial because they can increase the risks of other mental health and substance use disorders without appropriate psychosocial interventions and treatment. However, diagnosing DBDs is challenging as they are often comorbid with other disorders, such as attention-deficit/hyperactivity disorder, anxiety, and depression. In this study, a multimodal ensemble 3D convolutional neural network (CNN) deep learning model was used to classify children with DBDs and typically developing children. The study participants included 419 girls and 681 boys, aged 108 to 131 months who were enrolled in the Adolescent Brain Cognitive Development Study. Children were grouped based on the presence of DBDs (n=550) and typically developing (n=550); assessments were based on the scores from the Child Behavior Checklist and on the Schedule for Affective Disorders and Schizophrenia for School-age Children–Present and Lifetime version for DSM-5. The diffusion, structural, and resting-state functional magnetic resonance imaging (rs-fMRI) data were used as input data to the 3D CNN. The model achieved 72% accuracy in classifying children with DBDs with 70% sensitivity and 72% specificity. In addition, the discriminative power of the classifier was investigated by delineating the cortical and subcortical regions primarily involved in the prediction of DBDs using a gradient class activation map. The classification results were compared with those obtained using the three neuroimaging modalities individually, and a connectome-based graph CNN and a multi-scale recurrent neural network using only the rs-fMRI data.

Graph auto-encoding brain networks with applications to analyzing large-scale brain imaging datasets

Liu M, Zhang Z, Dunson DB. Graph auto-encoding brain networks with applications to analyzing large-scale brain imaging datasets. Neuroimage. 2021 Nov 22:118750. doi: 10.1016/j.neuroimage.2021.118750. Epub ahead of print. PMID: 34823023.

Brain structural associations with depression in a large early adolescent sample (the ABCD study®)

Shen X, MacSweeney N, Chan SWY, Barbu MC, Adams MJ, Lawrie SM, Romaniuk L, McIntosh AM, Whalley HC. Brain structural associations with depression in a large early adolescent sample (the ABCD study®), EClinicalMedicine, Volume 42, 2021, 101204, ISSN 2589-5370, https://doi.org/10.1016/j.eclinm.2021.101204.

Background
Depression is the leading cause of disability worldwide with > 50% of cases emerging before the age of 25 years. Large-scale neuroimaging studies in depression implicate robust structural brain differences in the disorder. However, most studies have been conducted in adults and therefore, the temporal origins of depression-related imaging features remain largely unknown. This has important implications for understanding aetiology and informing timings of potential intervention.

Methods
Here, we examine associations between brain structure (cortical metrics and white matter microstructural integrity) and depression ratings (from caregiver and child), in a large sample (N = 8634) of early adolescents (9 to 11 years old) from the US-based, Adolescent Brain and Cognitive Development (ABCD) Study®. Data was collected from 2016 to 2018.

Findings
We report significantly decreased global cortical and white matter metrics, and regionally in frontal, limbic and temporal areas in adolescent depression (Cohen’s d = -0⋅018 to -0⋅041, β = -0·019 to -0⋅057). Further, we report consistently stronger imaging associations for caregiver-reported compared to child-reported depression ratings. Divergences between reports (caregiver vs child) were found to significantly relate to negative socio-environmental factors (e.g., family conflict, absolute β = 0⋅048 to 0⋅169).

Interpretation
Depression ratings in early adolescence were associated with similar imaging findings to those seen in adult depression samples, suggesting neuroanatomical abnormalities may be present early in the disease course, arguing for the importance of early intervention. Associations between socio-environmental factors and reporter discrepancy warrant further consideration, both in the wider context of the assessment of adolescent psychopathology, and in relation to their role in aetiology.

Minding the Gap: Adolescent and Parent/Caregiver Reporter Discrepancies on Symptom Presence, Impact of Covariates, and Clinical Implications

Ford SH, McCoy TP. Minding the Gap: Adolescent and Parent/Caregiver Reporter Discrepancies on Symptom Presence, Impact of Covariates, and Clinical Implications. J Pediatr Health Care. 2021 Nov 18:S0891-5245(21)00238-8. doi: 10.1016/j.pedhc.2021.09.010. Epub ahead of print. PMID: 34802858.

Brain signatures in children who contemplate suicide: Learning from the large-scale ABCD study

Wiglesworth, A., Falke, C., Fiecas, M., Luciana, M., Cullen, K., & Klimes-Dougan, B. (2021). Brain signatures in children who contemplate suicide: Learning from the large-scale ABCD study. Psychological Medicine, 1-10. doi:10.1017/S0033291721004074

Background
Suicide is the second-leading cause of death in youth. Understanding the neural correlates of suicide ideation (SI) in children is crucial to ongoing efforts to understand and prevent youth suicide. This study characterized key neural networks during rest and emotion task conditions in an epidemiologically informed sample of children who report current, past, or no SI.

Methods
Data are from the adolescent brain cognitive development study, including 8248 children (ages 9–10; mean age = 119.2 months; 49.2% female) recruited from the community. Resting-state functional connectivity (RSFC) and activation to emotional stimuli in the salience (SN) and default mode (DMN) networks were measured through fMRI. Self-reported SI and clinical profiles were gathered. We examined the replicability of our model results through repeated sub-sample reliability analyses.

Results
Children with current SI (2.0%), compared to those without any past SI, showed lower DMN RSFC (B = −0.267, p < 0.001) and lower DMN activation in response to negative as compared to neutral faces (B = −0.204, p = 0.010). These results were robust to the effects of MDD, ADHD, and medication use. Sub-sample analysis further supported the robustness of these results. We did not find support for differences in SN RSFC or in SN activation to positive or negative stimuli for children with or without SI.

Conclusions
Results from a large brain imaging study using robust statistical approaches suggest aberrant DMN functioning in children with current suicide ideation. Findings suggest potential mechanisms that may be targeted in suicide prevention efforts.

Persistent and distressing psychotic-like experiences using adolescent brain cognitive development℠ study data

Karcher NR, Loewy RL, Savill M, Avenevoli S, Huber RS, Makowski C, Sher KJ, & Barch DM. Persistent and distressing psychotic-like experiences using adolescent brain cognitive development℠ study data. Mol Psychiatry (Nov. 16, 2021). https://doi.org/10.1038/s41380-021-01373-x

Childhood psychotic-like experiences (PLEs) are associated with a range of impairments; a subset of children experiencing PLEs will develop psychiatric disorders, including psychotic disorders. A potential distinguishing factor between benign PLEs versus PLEs that are clinically relevant is whether PLEs are distressing and/or persistent. The current study used three waves of Adolescent Brain Cognitive Development℠ (ABCD) study PLEs assessments to examine the extent to which persistent and/or distressing PLEs were associated with relevant baseline risk factors (e.g., cognition) and functioning/mental health service utilization domains. Four groups varying in PLE persistence and distress endorsement were created based on all available data in ABCD Release 3.0, with group membership not contingent on complete data: persistent distressing PLEs (n = 272), transient distressing PLEs (n = 298), persistent non-distressing PLEs (n = 221), and transient non-distressing PLEs (n = 536) groups. Using hierarchical linear models, results indicated youth with distressing PLEs, whether transient or persistent, showed delayed developmental milestones (β = 0.074, 95%CI:0.013,0.134) and altered structural MRI metrics (β = −0.0525, 95%CI:−0.100,−0.005). Importantly, distress interacted with PLEs persistence for the domains of functioning/mental health service utilization (β = 0.079, 95%CI:0.016,0.141), other reported psychopathology (β = 0.101, 95%CI:0.030,0.170), cognition (β = −0.052, 95%CI:0.−0.099,−0.002), and environmental adversity (β = 0.045, 95%CI:0.003,0.0.86; although no family history effects), with the interaction characterized by greatest impairment in the persistent distressing PLEs group. These results have implications for disentangling the importance of distress and persistence for PLEs with regards to impairments, including functional, pathophysiological, and environmental outcomes. These novel longitudinal data underscore that it is often only in the context of distress that persistent PLEs were related to impairments.

Neural vulnerability and hurricane-related media are associated with post-traumatic stress in youth

Dick, A.S., Silva, K., Gonzalez, R. et al. Neural vulnerability and hurricane-related media are associated with post-traumatic stress in youth. Nat Hum Behav 5, 1578–1589 (2021). https://doi.org/10.1038/s41562-021-01216-3

The human toll of disasters extends beyond death, injury and loss. Post-traumatic stress (PTS) can be common among directly exposed individuals, and children are particularly vulnerable. Even children far removed from harm’s way report PTS, and media-based exposure may partially account for this phenomenon. In this study, we examine this issue using data from nearly 400 9- to 11-year-old children collected before and after Hurricane Irma, evaluating whether pre-existing neural patterns moderate associations between hurricane experiences and later PTS. The ‘dose’ of both self-reported objective exposure and media exposure predicted PTS, the latter even among children far from the hurricane. Furthermore, neural responses in brain regions associated with anxiety and stress conferred particular vulnerability. For example, heightened amygdala reactivity to fearful stimuli moderated the association between self-reported media exposure and PTS. Collectively, these findings show that for some youth with measurable vulnerability, consuming extensive disaster-related media may offer an alternative pathway to disaster exposure that transcends geography and objective risk.

Widespread attenuating changes in brain connectivity associated with the general factor of psychopathology in 9- and 10-year olds

Sripada C, Angstadt M, Taxali A, Kessler D, Greathouse T, Rutherford S, Clark DA, Hyde LW, Weigard A, Brislin SJ, Hicks B, Heitzeg M. Widespread attenuating changes in brain connectivity associated with the general factor of psychopathology in 9- and 10-year olds. Transl Psychiatry. 2021 Nov 9;11(1):575. doi: 10.1038/s41398-021-01708-w. PMID: 34753911.

Convergent research identifies a general factor («P factor») that confers transdiagnostic risk for psychopathology. Large-scale networks are key organizational units of the human brain. However, studies of altered network connectivity patterns associated with the P factor are limited, especially in early adolescence when most mental disorders are first emerging. We studied 11,875 9- and 10-year olds from the Adolescent Brain and Cognitive Development (ABCD) study, of whom 6593 had high-quality resting-state scans. Network contingency analysis was used to identify altered interconnections associated with the P factor among 16 large-scale networks. These connectivity changes were then further characterized with quadrant analysis that quantified the directionality of P factor effects in relation to neurotypical patterns of positive versus negative connectivity across connections. The results showed that the P factor was associated with altered connectivity across 28 network cells (i.e., sets of connections linking pairs of networks); pPERMUTATION values < 0.05 FDR-corrected for multiple comparisons. Higher P factor scores were associated with hypoconnectivity within default network and hyperconnectivity between default network and multiple control networks. Among connections within these 28 significant cells, the P factor was predominantly associated with «attenuating» effects (67%; pPERMUTATION < 0.0002), i.e., reduced connectivity at neurotypically positive connections and increased connectivity at neurotypically negative connections. These results demonstrate that the general factor of psychopathology produces attenuating changes across multiple networks including default network, involved in spontaneous responses, and control networks involved in cognitive control. Moreover, they clarify mechanisms of transdiagnostic risk for psychopathology and invite further research into developmental causes of distributed attenuated connectivity.

Racism May Interrupt Age-related Brain Growth of African American Children in the United States

Assari S, Mincy R. Racism May Interrupt Age-related Brain Growth of African American Children in the United States. J Pediatr Child Health Care. 2021;6(3):1047. Epub 2021 Nov 9. PMID: 34966911; PMCID: PMC8713722.

Background: Considerable research has documented age-related growth in brain size as a marker of normal brain development. This is particularly important because brain volume has a significant role in overall cognitive performance. However, less research is done on whether age-related changes in the global brain volume differ across diverse racial and ethnic groups. We hypothesized that age-related growth in brain size would be disrupted in African American children who are historically affected by racism.

Purpose: Considering race as a proxy of racism rather than genetics, this study tested racial and ethnic differences in the effects of age on global brain volume using structural brain imaging data. Built on a sociological, rather than a biological theory, we built our study on Marginalization-related Diminished Returns (MDRs) framework, which argues that under racism, resources and assets are less effective for social groups that are historically racialized, discriminated against, marginalized, and segregated. Considering age as an asset/resource that increases the global brain volume, we expected weaker effects of age on overall brain size of African American and Hispanic children, than White and non-Hispanic children, again as a result of racism.

Methods: We borrowed the structural Magnetic Resonance Imaging (sMRI) data from the Children Brain Cognitive Development (ABCD) study, which included 9,311 9-10 year old children. The independent variable was the child’s age treated as a continuous measure (in months). The primary outcome was global brain volume. Sex, parental employment, parental education, household income, and parental marital status were the covariates. Race and ethnicity, as proxies of racism, were the moderators. To analyze the data, we used linear regression models.

Results: Age was positively associated with the global brain size in children. In line with the MDRs, the positive association between age and global brain volume was weaker for African American than White children, while family structure, sex, and family socioeconomic status was controlled.

Conclusions: Under racism, age has unequal effects on global brain size of diverse racial groups. In line with the MDRs, we observe diminished age-related growth of the brain for African American children, which documents detrimental effects of racism. For White children who are not affected by racism, age makes a large difference regarding global brain volume. Age-related growth of global brain size is diminished in African American children, whose daily lives are shaped by racism. School and residential segregation may have a role in reducing the effect of age on children’s brain growth in African American families. The results should not be interpreted as inferiority of one group but social processes that hinder normal development of a historically oppressed group.

Brain-wide functional connectivity patterns support general cognitive ability and mediate effects of socioeconomic status in youth

Sripada C, Angstadt M, Taxali A, Clark DA, Greathouse T, Rutherford S, Dickens JR, Shedden K, Gard AM, Hyde LW, Weigard A, Heitzeg M. Brain-wide functional connectivity patterns support general cognitive ability and mediate effects of socioeconomic status in youth. Transl Psychiatry. 2021 Nov 8;11(1):571. doi: 10.1038/s41398-021-01704-0. PMID: 34750359.

General cognitive ability (GCA) is an individual difference dimension linked to important academic, occupational, and health-related outcomes and its development is strongly linked to differences in socioeconomic status (SES). Complex abilities of the human brain are realized through interconnections among distributed brain regions, but brain-wide connectivity patterns associated with GCA in youth, and the influence of SES on these connectivity patterns, are poorly understood. The present study examined functional connectomes from 5937 9- and 10-year-olds in the Adolescent Brain Cognitive Development (ABCD) multi-site study. Using multivariate predictive modeling methods, we identified whole-brain functional connectivity patterns linked to GCA. In leave-one-site-out cross-validation, we found these connectivity patterns exhibited strong and statistically reliable generalization at 19 out of 19 held-out sites accounting for 18.0% of the variance in GCA scores (cross-validated partial η2). GCA-related connections were remarkably dispersed across brain networks: across 120 sets of connections linking pairs of large-scale networks, significantly elevated GCA-related connectivity was found in 110 of them, and differences in levels of GCA-related connectivity across brain networks were notably modest. Consistent with prior work, socioeconomic status was a strong predictor of GCA in this sample, and we found that distributed GCA-related brain connectivity patterns significantly statistically mediated this relationship (mean proportion mediated: 15.6%, p < 2 × 10-16). These results demonstrate that socioeconomic status and GCA are related to broad and diffuse differences in functional connectivity architecture during early adolescence, potentially suggesting a mechanism through which socioeconomic status influences cognitive development.

Pubertal Timing and Functional Neurodevelopmental Alterations Independently Mediate the Effect of Family Conflict on Adolescent Psychopathology

Petrican R, Miles S, Rudd L, Wasiewska W, Graham KS, Lawrence AD (2021). Pubertal Timing and Functional Neurodevelopmental Alterations Independently Mediate the Effect of Family Conflict on Adolescent Psychopathology, Developmental Cognitive Neuroscience, Volume 52, December 2021, 101032, 101032, ISSN 1878-9293, https://doi.org/10.1016/j.dcn.2021.101032.

This study tested the hypothesis that early life adversity (ELA) heightens psychopathology risk by concurrently altering pubertal and neurodevelopmental timing, and associated gene transcription signatures. Analyses focused on threat (family conflict/neighbourhood crime) and deprivation-related ELAs (parental inattentiveness/unmet material needs), using longitudinal data from 1514 biologically unrelated youths in the Adolescent Brain and Cognitive Development (ABCD) study. Typical developmental changes in white matter microstructure corresponded to widespread BOLD signal variability (BOLDsv) increases (linked to cell communication and biosynthesis genes) and region-specific task-related BOLDsv increases/decreases (linked to signal transduction, immune and external environmental response genes). Increasing resting-state (RS), but decreasing task-related BOLDsv predicted normative functional network segregation. Family conflict was the strongest concurrent and prospective contributor to psychopathology, while material deprivation constituted an additive risk factor. ELA-linked psychopathology was predicted by higher Time 1 threat-evoked BOLDSV (associated with axonal development, myelination, cell differentiation and signal transduction genes), reduced Time 2 RS BOLDsv (associated with cell metabolism and attention genes) and greater Time 1 to Time 2 control/attention network segregation. Earlier pubertal timing and neurodevelopmental alterations independently mediated ELA effects on psychopathology. Our results underscore the differential roles of the immediate and wider external environment(s) in concurrent and longer-term ELA consequences.

Greater radiologic evidence of hypothalamic gliosis predicts adiposity gain in children at risk for obesity

Sewaybricker LE, Kee S, Melhorn SJ, Schur EA. Greater radiologic evidence of hypothalamic gliosis predicts adiposity gain in children at risk for obesity. Obesity (Silver Spring). 2021 Nov;29(11):1770-1779. doi: 10.1002/oby.23286. PMID: 34734493.

Objective: This study investigated, in a large pediatric population, whether magnetic resonance imaging (MRI) evidence of mediobasal hypothalamic (MBH) gliosis is associated with baseline or change over 1 year in body adiposity.

Methods: Cross-sectional and prospective cohort analyses were conducted within the Adolescent Brain Cognitive Development Study. Study 1 included 169 children with usable baseline T2-weighted MRI images and anthropometrics from baseline and 1-year follow-up study visits. Signal ratios compared T2 signal intensity in MBH and two reference regions (amygdala [AMY] and putamen) as a measure of MBH gliosis. Study 2 included a distinct group of 238 children with overweight or obesity to confirm initial findings in an independent sample.

Results: In Study 1, MBH/AMY signal ratio was positively associated with BMI z score (β = 4.27, p < 0.001). A significant interaction for the association of MBH/AMY signal ratio with change in BMI z score suggested that relationships differed by baseline weight status. Study 2 found that higher MBH/AMY signal ratios associated with an increase in BMI z score for children with overweight (β = 0.58, p = 0.01), but not those with obesity (β = 0.02, p = 0.91).

Conclusions: Greater evidence of hypothalamic gliosis by MRI is associated with baseline BMI z score and predicts adiposity gain in young children at risk of obesity.

Cingulo-opercular and Cingulo-parietal Brain Networks Functional Connectivity in Pre-adolescents: Multiplicative Effects of Race, Ethnicity, and Parental Education

Assari S. Cingulo-opercular and Cingulo-parietal Brain Networks Functional Connectivity in Pre-adolescents: Multiplicative Effects of Race, Ethnicity, and Parental Education. Res Health Sci. 2021;6(2):76-99. doi: 10.22158/rhs.v6n2p76. PMID: 34734154; PMCID: PMC8562861.

Introduction: A growing body of research has shown a diminished association between socioeconomic status (SES) indicators and a wide range of neuroimaging indicators for racial and ethnic minorities compared to majority groups. However, less is known about these effects for resting-state functional connectivity between various brain networks.

Purpose: This study investigated racial and ethnic variation in the correlation between parental education and resting-state functional connectivity between the cingulo-opercular (CO) and cingulo-parietal (CP) networks in children.

Methods: This cross-sectional study used data from the Adolescent Brain Cognitive Development (ABCD) study; we analyzed the resting-state functional Magnetic Resonance Imaging (rsfMRI) data of 8,464 American pre-adolescents between the ages of 9 and 10. The main outcome measured was resting-state functional connectivity between the CO and CP networks calculated using rsfMRI. The independent variable was parental education, which was treated as a nominal variable. Age, sex, and family marital status were the study covariates. Race and ethnicity were the moderators. Mixed-effects regression models were used for data analysis, with and without interaction terms between parental education and race and ethnicity.

Results: Higher parental education was associated with higher resting-state functional connectivity between the CO and CP networks. Race and ethnicity both showed statistically significant interactions with parental education on children’s resting-state functional connectivity between CO and CP networks, suggesting that the correlation between parental education and the resting-state functional connectivity was significantly weaker for Black and Hispanic pre-adolescents compared to White and non-Hispanic pre-adolescents.

Conclusions: In line with the Minorities’ Diminished Returns theory, the association between parental education and pre-adolescents resting-state functional connectivity between CO and CP networks may be weaker in Black and Hispanic children than in White and non-Hispanic children. The weaker link between parental education and brain functional connectivity for Blacks and Hispanics than for Whites and non-Hispanics may reflect racism, racialization, and social stratification that collectively minimize the returns of SES indicators, such as parental education for non-Whites, who become others in the US.

Smaller Hippocampal Volume Among Black and Latinx Youth Living in High-Stigma Contexts

Hatzenbuehler ML, Weissman DG, McKetta S, Lattanner MR, Ford JV, Barch DM, McLaughlin KA. Smaller Hippocampal Volume Among Black and Latinx Youth Living in High-Stigma Contexts. J Am Acad Child Adolesc Psychiatry. 2021 Sep 2:S0890-8567(21)01361-7. doi: 10.1016/j.jaac.2021.08.017. Epub ahead of print. PMID: 34481917.

Objective: To determine whether structural and individual forms of stigma are associated with neurodevelopment in children.

Method: Stigma related to gender, race, and Latinx ethnicity was measured at the structural level using objective state-level indicators of social policies and prejudicial attitudes and at the individual level using self-reports of perceived discrimination. Respective associations of stigma with hippocampal volume and amygdala reactivity to threat were examined using data from the Adolescent Brain Cognitive Development (ABCD) Study (N ¼ 11,534, mean age 9.9 years), the first multisite neuroimaging study that provided substantial variability in sociopolitical contexts and that included individuallevel measures of stigma among youth.

Results: In a preregistered analysis, Black (B ¼ 58.26, p ¼ .023) and Latinx (B ¼ 40.10, p ¼ .044) youths in higher (vs lower) structural stigma contexts were found to have smaller hippocampal volume, controlling for total intracranial volume, demographics, and family socioeconomic status. This association was also observed at a trend-level among girls (p ¼ .082). The magnitude of the difference in hippocampal volume between high and low structural stigma states was equivalent to the predicted impact of a $20,000 difference in annual family income in this sample. As hypothesized, structural stigma was not associated with hippocampal volume in nonstigmatized youths, providing evidence of specificity. Perceived discrimination was unrelated to hippocampal volume in stigmatized groups. No associations between perceived discrimination or structural stigma and amygdala reactivity to threat were observed.

Conclusion: This study provides novel evidence that an objective measure of structural stigma may be more strongly related to hippocampal volume than subjective perceptions of stigma, suggesting that contextual approaches to stigma could yield new insights into neurodevelopment among marginalized youth.

Concussion Among Children in the United States General Population: Incidence and Risk Factors

Cook NE, Iverson GL. Concussion Among Children in the United States General Population: Incidence and Risk Factors. Front Neurol. 2021 Nov 1;12:773927. doi: 10.3389/fneur.2021.773927. PMID: 34790165; PMCID: PMC8591091.

The objective of this study was to examine the incidence of concussion and risk factors for sustaining concussion among children from the United States general population. This prospective cohort study used data from the Adolescent Brain Cognitive Development (ABCD) Study®. Children were recruited from schools across the US, sampled to reflect the sociodemographic variation of the US population. The current sample includes 11,013 children aged 9 to 10 years old (47.6% girls; 65.5% White) who were prospectively followed for an average of 1 year (mean = 367.9 days, SD = 40.8, range 249-601). The primary outcome was caregiver-reported concussion during a 1 year follow-up period. Logistic regression was used to determine which potential clinical, health history, and behavioral characteristics (assessed at baseline) were prospectively associated with concussion. In the 1 year follow-up period between ages 10 and 11, 1 in 100 children (n = 123, 1.1%) sustained a concussion. In univariate models, three baseline predictors (ADHD, prior concussion, and accident proneness) were significantly associated with sustaining a concussion. In a multivariate model, controlling for all other predictors, only prior concussion remained significantly associated with the occurrence of a concussion during the observation period (Odds Ratio = 5.49, 95% CI: 3.40-8.87). The most robust and only independent prospective predictor of sustaining a concussion was history of a prior concussion. History of concussion is associated with 5.5 times greater odds of sustaining concussion between ages 10 and 11 among children from the general US population.

Screen Time Use Among US Adolescents During the COVID-19 Pandemic: Findings From the Adolescent Brain Cognitive Development (ABCD) Study

Nagata JM, Cortez CA, Cattle CJ, Ganson KT, Iyer P, Bibbins-Domingo K, Baker FC. Screen Time Use Among US Adolescents During the COVID-19 Pandemic: Findings From the Adolescent Brain Cognitive Development (ABCD) Study. JAMA Pediatr. 2021 Nov 1. doi: 10.1001/jamapediatrics.2021.4334. Epub ahead of print. PMID: 34724543.

Methods
Cross-sectional data from the May 2020 COVID-19 survey (COVID-19 Rapid Response Research Release) from the Adolescent Brain Cognitive Development (ABCD) Study were analyzed. The sample consisted of 5412 adolescents predominantly aged 12 to 13 years. Centralized institutional review board approval was obtained from the University of California, San Diego. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. Written informed consent and assent were obtained from a parent or guardian and the child, respectively, to participate in the ABCD study.

Screen use for the following modalities was determined using adolescents’ self-reported hours of use on a typical day, excluding hours spent on school-related work: multiple-player gaming, single-player gaming, texting, social media, video chatting, browsing the internet, and watching or streaming movies, videos, or television shows.5 Total typical daily screen use, excluding schoolwork, was calculated as the sum. Multiple linear regression analyses estimated associations between mental health and resiliency factors (eMethods in the Supplement provides the measures) and total screen use, after adjustment for potential confounders including sex, race and ethnicity (as self-reported from a list of categories), annual household income, parent educational level, and study site. Analyses were conducted in 2021 using Stata 15.1, weighting data to approximate the American Community Survey by the US Census. Testing was 2-sided, and P < .05 was considered statistically significant.

Results
Among the 5412 adolescents included in our sample, 50.7% were female and 49.3% were male. The sample was racially and ethnically diverse (7.2% Asian; 11.1% Black; 17.2% Hispanic, Latina, and Latino; 2.5% Native American; 60.6% White; and 1.4% self-reported as other). Adolescents reported a mean (SD) of 7.70 (5.74) h/d of screen use, mostly spent on watching or streaming videos, movies, or television shows (2.42 [2.45] h/d), multiple-player gaming (1.44 [2.21] h/d), and single-player gaming (1.17 [1.82] h/d). The mean and SD screen use time for each modality by sociodemographic characteristics are given in Table 1. In adjusted models (Table 2), poorer mental health (B, 0.29; 95% CI, 0.06-0.52; P = .01) and greater perceived stress (B, 0.67; 95% CI, 0.43-0.91; P < .001) were associated with higher total screen use, while more social support (B, −0.32; 95% CI, −0.59 to −0.04; P = .02) and coping behaviors (B, −0.17; 95% CI, −0.26 to −0.09; P < .001) were associated with lower total screen use.

Discussion
In this cross-sectional study of a large, national sample of adolescents surveyed early in the COVID-19 pandemic, we found that the mean total daily screen use was 7.70 h/d. This is higher than prepandemic estimates (3.8 h/d) from the same cohort at baseline, although younger age and slightly different screen time categories could also account for differences.6 Despite the gradual reversal of quarantine restrictions, studies have suggested that screen use may remain persistently elevated.4 Screen time disparities across racial, ethnic, and income groups in adolescents have been reported previously and may be due to structural and systemic racism–driven factors (eg, built environment, access to financial resources, and digital media education)—all of which have been amplified in the COVID-19 pandemic.2 Different screen use modalities may have differential positive or negative consequences for adolescents’ well-being during the COVID-19 pandemic. Adolescents experiencing stress and poor mental health may use screens to manage negative feelings or withdraw from stressors. Although some screen modalities may be used to promote social connection, higher coping behaviors and social support in this sample were associated with lower total screen usage. Limitations of this study include the use of self-reported data. Furthermore, adolescents often multitask on screens; thus, the computed total could be an overestimate. Future studies should examine screen use trends as pandemic restrictions are lifted and also explore mechanisms to prevent sociodemographic disparities.

Demographic and Mental Health Assessments in the Adolescent Brain and Cognitive Development Study: Updates and Age-Related Trajectories

Deanna M. Barch, Matthew D. Albaugh, Arielle Baskin-Sommers, Brittany E. Bryant, Duncan B. Clark, Anthony Steven Dick, Eric Feczko, John J. Foxe, Dylan G. Gee, Jay Giedd, Meyer D. Glantz, James J. Hudziak, Nicole R. Karcher, Kimberly LeBlanc, Melanie Maddox, Erin C. McGlade, Carrie Mulford, Bonnie J. Nagel, Gretchen Neigh, Clare E Palmer, Alexandra S. Potter, Kenneth J. Sher, Susan F. Tapert, Wesley K. Thompson, Laili Xie (2021). Demographic and Mental Health Assessments in the Adolescent Brain and Cognitive Development Study: Updates and Age-Related Trajectories, Developmental Cognitive Neuroscience, Volume 52, December 2021, 101031, ISSN 1878-9293, https://doi.org/10.1016/j.dcn.2021.101031.

The Adolescent Brain Cognitive Development (ABCD) Study of 11,880 youth incorporates a comprehensive range of measures assessing predictors and outcomes related to mental health across childhood and adolescence in participating youth, as well as information about family mental health history. We have previously described the logic and content of the mental health assessment battery at Baseline and 1-year follow-up. Here, we describe changes to that battery and issues and clarifications that have emerged, as well as additions to the mental health battery at the 2-, 3-, 4-, and 5-year follow-ups. We capitalize on the recent release of longitudinal data for caregiver and youth report of mental health data to evaluate trajectories of dimensions of psychopathology as a function of demographic factors. For both caregiver and self-reported mental health symptoms, males showed age-related decreases in internalizing and externalizing symptoms, while females showed an increase in internalizing symptoms with age. Multiple indicators of socioeconomic status (caregiver education, family income, financial adversity, neighborhood poverty) accounted for unique variance in both caregiver and youth-reported externalizing and internalizing symptoms. These data highlight the importance of examining developmental trajectories of mental health as a function of key factors such as sex and socioeconomic environment.

Contributions of PTSD polygenic risk and environmental stress to suicidality in preadolescents

Daskalakis NP, Schultz LM, Visoki E, Moore TM, Argabright ST, Harnett NG, DiDomenico GE, Warrier V, Almasy L, Barzilay R. Contributions of PTSD polygenic risk and environmental stress to suicidality in preadolescents. Neurobiol Stress. 2021 Oct 27;15:100411. doi: 10.1016/j.ynstr.2021.100411. PMID: 34765698; PMCID: PMC8569631.

Suicidal ideation and attempts (i.e., suicidality) are complex behaviors driven by environmental stress, genetic susceptibility, and their interaction. Preadolescent suicidality is a major health problem with rising rates, yet its underlying biology is understudied. Here we studied effects of genetic stress susceptibility, approximated by the polygenic risk score (PRS) for post-traumatic-stress-disorder (PTSD), on preadolescent suicidality in participants from the Adolescent Brain Cognitive Development (ABCD) Study®. We further evaluated PTSD-PRS effects on suicidality in the presence of environmental stressors that are established suicide risk factors. Analyses included both European and African ancestry participants using PRS calculated based on summary statistics from ancestry-specific genome-wide association studies. In European ancestry participants (N = 4,619, n = 378 suicidal), PTSD-PRS was associated with preadolescent suicidality (odds ratio [OR] = 1.12, 95%CI 1-1.25, p = 0.038). Results in African ancestry participants (N = 1,334, n = 130 suicidal) showed a similar direction but were not statistically significant (OR = 1.21, 95%CI 0.93-1.57, p = 0.153). Sensitivity analyses using non-psychiatric polygenic score for height and using cross-ancestry PTSD-PRS did not reveal any association with suicidality, supporting the specificity of the association of ancestry-specific PTSD-PRS with suicidality. Environmental stressors were robustly associated with suicidality across ancestries with moderate effect size for negative life events and family conflict (OR 1.27-1.6); and with large effect size (OR ∼ 4) for sexual-orientation discrimination. When combined with environmental factors, PTSD-PRS showed marginal additive effects in explaining variability in suicidality, with no evidence for G × E interaction. Results support use of cross-phenotype PRS, specifically stress-susceptibility, as a genetic marker for suicidality risk early in the lifespan.

Shorter Duration and Lower Quality Sleep Have Widespread Detrimental Effects on Developing Functional Brain Networks in Early Adolescence

Skylar J Brooks, Eliot S Katz, Catherine Stamoulis, Shorter Duration and Lower Quality Sleep Have Widespread Detrimental Effects on Developing Functional Brain Networks in Early Adolescence, Cerebral Cortex Communications, 2021; tgab062, https://doi.org/10.1093/texcom/tgab062

Sleep is critical for cognitive health, especially during complex developmental periods such as adolescence. However, its effects on maturating brain networks that support cognitive function are only partially understood. We investigated the impact of shorter duration and reduced quality sleep, common stressors during development, on functional network properties in early adolescence—a period of significant neural maturation, using resting-state fMRI from 5566 children (median age = 120.0 months; 52.1% females) in the Adolescent Brain Cognitive Development (ABCD) cohort. Decreased sleep duration, increased sleep latency, frequent waking up at night, and sleep-disordered breathing symptoms were associated with lower topological efficiency, flexibility, and robustness of visual, sensorimotor, attention, fronto-parietal control, default-mode and/or limbic networks, and with aberrant changes in the thalamus, basal ganglia, hippocampus and cerebellum (p < 0.05). These widespread effects, many of which were BMI-independent, suggest that unhealthy sleep in early adolescence may impair neural information processing and integration across incompletely developed networks, potentially leading to deficits in their cognitive correlates, including attention, reward, emotion processing and regulation, memory, and executive control. Shorter sleep duration, frequent snoring, difficulty waking up and daytime sleepiness had additional detrimental network effects in non-white participants, indicating racial disparities in the influence of sleep metrics.

Large-scale functional brain networks of maladaptive childhood aggression identified by connectome-based predictive modeling

Ibrahim K, Noble S, He G, Lacadie C, Crowley MJ, McCarthy G, Scheinost D, Sukhodolsky DG. Large-scale functional brain networks of maladaptive childhood aggression identified by connectome-based predictive modeling. Mol Psychiatry. 2021 Oct 25. doi: 10.1038/s41380-021-01317-5. Epub ahead of print. PMID: 34690348.

Disruptions in frontoparietal networks supporting emotion regulation have been long implicated in maladaptive childhood aggression. However, the association of connectivity between large-scale functional networks with aggressive behavior has not been tested. The present study examined whether the functional organization of the connectome predicts severity of aggression in children. This cross-sectional study included a transdiagnostic sample of 100 children with aggressive behavior (27 females) and 29 healthy controls without aggression or psychiatric disorders (13 females). Severity of aggression was indexed by the total score on the parent-rated Reactive-Proactive Aggression Questionnaire. During fMRI, participants completed a face emotion perception task of fearful and calm faces. Connectome-based predictive modeling with internal cross-validation was conducted to identify brain networks that predicted aggression severity. The replication and generalizability of the aggression predictive model was then tested in an independent sample of children from the Adolescent Brain Cognitive Development (ABCD) study. Connectivity predictive of aggression was identified within and between networks implicated in cognitive control (medial-frontal, frontoparietal), social functioning (default mode, salience), and emotion processing (subcortical, sensorimotor) (r = 0.31, RMSE = 9.05, p = 0.005). Out-of-sample replication (p < 0.002) and generalization (p = 0.007) of findings predicting aggression from the functional connectome was demonstrated in an independent sample of children from the ABCD study (n = 1791; n = 1701). Individual differences in large-scale functional networks contribute to variability in maladaptive aggression in children with psychiatric disorders. Linking these individual differences in the connectome to variation in behavioral phenotypes will advance identification of neural biomarkers of maladaptive childhood aggression to inform targeted treatments.

Associations of Family Distress, Family Income, and Acculturation on Pediatric Cognitive Performance Using the NIH Toolbox: Implications for Clinical and Research Settings

Thompson RC, Montena AL, Liu K, Watson J, Warren SL. Associations of Family Distress, Family Income, and Acculturation on Pediatric Cognitive Performance Using the NIH Toolbox: Implications for Clinical and Research Settings. Arch Clin Neuropsychol. 2021 Oct 19:acab082. doi: 10.1093/arclin/acab082. Epub ahead of print. PMID: 34664626.

Objective: There is a growing recognition that the use of conventional norms (e.g., age, sex, years of education, race) as proxies to capture a broad range of sociocultural variability on cognitive performance is suboptimal, limiting sample representativeness. The present study evaluated the incremental utility of family income, family conflict, and acculturation beyond the established associations of age, gender,maternal years of education, and race on cognitive performance.

Method: Hierarchical linear regressions evaluated the incremental utility of sociocultural factors on National Institutes of Health Toolbox in a nationally representative sample of pre-adolescent children (n = 11,878; Mage = 10.0 years; Adolescent Brain Cognitive Development Study). A regression-based norming procedure was implemented for significant models. Paired sample t-tests were used to compare original and newly created demographically corrected T-scores.

Results: Nearly all regression models predicted performance on the NIH-TB subtests and composite scores (p < .005). Greater family income and lower family conflict predicted better performance, although the effect sizes were small by traditional standards. Acculturation scores did not explain additional variance in cognitive performance. Lastly, there were no significant differences between the original and newly created demographically corrected T-scores (Mdiff < 0.50).

Conclusions: The present study highlights that, although family income, family conflict, and acculturation have been shown to routinely influence cognitive performance in preadolescent children, the NIH-TB appears to be highly robust to individual differences in sociocultural factors in children between ages 9 and 10. Contextual and temporal implications of the present results are discussed.

Passive Sensing of Preteens’ Smartphone Use: An Adolescent Brain Cognitive Development (ABCD) Cohort Substudy

Wade N, Ortigara JM, Sullivan RM, Tomko RL, Breslin FJ, Baker FC, Fuemmeler BF, Delrahim Howlett K, Lisdahl KM, Marshall AT, Mason MJ, Neale MC, Squeglia LM, Wolff-Hughes DL, Tapert SF, Bagot KS; ABCD Novel Technologies Workgroup. Passive Sensing of Preteens’ Smartphone Use: An Adolescent Brain Cognitive Development (ABCD) Cohort Substudy. JMIR Ment Health. 2021 Oct 18;8(10):e29426. doi: 10.2196/29426. PMID: 34661541.

Background: Concerns abound regarding childhood smartphone use, but studies to date have largely relied on self-reported screen use. Self-reporting of screen use is known to be misreported by pediatric samples and their parents, limiting the accurate determination of the impact of screen use on social, emotional, and cognitive development. Thus, a more passive, objective measurement of smartphone screen use among children is needed.

Objective: This study aims to passively sense smartphone screen use by time and types of apps used in a pilot sample of children and to assess the feasibility of passive sensing in a larger longitudinal sample.

Methods: The Adolescent Brain Cognitive Development (ABCD) study used passive, objective phone app methods for assessing smartphone screen use over 4 weeks in 2019-2020 in a subsample of 67 participants (aged 11-12 years; 31/67, 46% female; 23/67, 34% White). Children and their parents both reported average smartphone screen use before and after the study period, and they completed a questionnaire regarding the acceptability of the study protocol. Descriptive statistics for smartphone screen use, app use, and protocol feasibility and acceptability were reviewed. Analyses of variance were run to assess differences in categorical app use by demographics. Self-report and parent report were correlated with passive sensing data.

Results: Self-report of smartphone screen use was partly consistent with objective measurement (r=0.49), although objective data indicated that children used their phones more than they reported. Passive sensing revealed the most common types of apps used were for streaming (mean 1 hour 57 minutes per day, SD 1 hour 32 minutes), communication (mean 48 minutes per day, SD 1 hour 17 minutes), gaming (mean 41 minutes per day, SD 41 minutes), and social media (mean 36 minutes per day, SD 1 hour 7 minutes). Passive sensing of smartphone screen use was generally acceptable to children (43/62, 69%) and parents (53/62, 85%).

Conclusions: The results of passive, objective sensing suggest that children use their phones more than they self-report. Therefore, use of more robust methods for objective data collection is necessary and feasible in pediatric samples. These data may then more accurately reflect the impact of smartphone screen use on behavioral and emotional functioning. Accordingly, the ABCD study is implementing a passive sensing protocol in the full ABCD cohort. Taken together, passive assessment with a phone app provided objective, low-burden, novel, informative data about preteen smartphone screen use.

An Update on the Assessment of Culture and Environment in the ABCD Study®: Emerging Literature and Protocol Updates over Three Measurement Waves

Gonzalez R, Thompson EL, Sanchez M, Morris A, Gonzalez MR, Feldstein Ewing SW, Mason MJ, Arroyo J, Howlett K, Tapert SF, Zucker RA (2021).  An Update on the Assessment of Culture and Environment in the ABCD Study®: Emerging Literature and Protocol Updates over Three Measurement Waves. Developmental Cognitive Neuroscience, Volume 52, December 2021, 101021, ISSN 1878-9293, https://doi.org/10.1016/j.dcn.2021.101021.

Advances in our understanding of risk and resilience factors in adolescent brain health and development increasingly demand a broad set of assessment tools that consider a youth’s peer, family, school, neighborhood, and cultural contexts in addition to neurobiological, genetic, and biomedical information. The Culture and Environment (CE) Workgroup (WG) of the Adolescent Brain Cognitive Development (ABCD) Study curates these important components of the protocol throughout ten years of planned data collection. In this report, the CE WG presents an update on the evolution of the ABCD Study® CE protocol since study inception (Zucker et al., 2018), as well as emerging findings that include CE measures. Background and measurement characteristics of instruments present in the study since baseline have already been described in our 2018 report, and therefore are only briefly described here. New measures introduced since baseline are described in more detail. Descriptive statistics on all measures are presented based on a total sample of 11,000+ youth and their caregivers assessed at baseline and the following two years. Psychometric properties of the measures, including longitudinal aspects of the data, are reported, along with considerations for future measurement waves. The CE WG ABCD® components are an essential part of the overall protocol that permits characterization of the unique cultural and social environment within which each developing brain is transactionally embedded.

Associations Among Negative Life Events, Changes in Cortico-Limbic Connectivity, and Psychopathology in the ABCD Study

Brieant AE, Sisk LM, Gee DG (2021). Associations Among Negative Life Events, Changes in Cortico-Limbic Connectivity, and Psychopathology in the ABCD Study. Developmental Cognitive Neuroscience. Available online 16 October 2021, 101022. Volume 52, December 2021, 101022. https://doi.org/10.1016/j.dcn.2021.101022.

Adversity exposure is a risk factor for psychopathology, which most frequently onsets during adolescence, and prior research has demonstrated that alterations in cortico-limbic connectivity may account in part for this association. In a sample of youth from the Adolescent Brain Cognitive Development (ABCD) Study (N = 4006), we tested a longitudinal structural equation model to examine the indirect effect of adversity exposure (negative life events) on later psychopathology via changes in cortico-limbic resting-state functional connectivity (rsFC). We also examined the potential protective effects of parental acceptance. Generally, cortico-limbic connectivity became more strongly negative between baseline and year 2 follow-up, suggesting that stronger negative correlations within these cortico-limbic networks may reflect a more mature phenotype. Exposure to a greater number of negative life events was associated with stronger negative cortico-limbic rsFC which, in turn, was associated with lower internalizing (but not externalizing) symptoms. The indirect effect of negative life events on internalizing symptoms via cortico-limbic rsFC was significant. Parental acceptance did not moderate the association between negative life events and rsFC. Our findings highlight how stressful childhood experiences may accelerate neurobiological maturation in specific cortico-limbic connections, potentially reflecting an adaptive process that protects against internalizing problems in the context of adversity.

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

Du J, Rolls ET, Gong W, Cao M, Vatansever D, Zhang J, Kang J, Cheng W, Feng J. Association between parental age, brain structure, and behavioral and cognitive problems in children. Mol Psychiatry. 2021 Oct 14. doi: 10.1038/s41380-021-01325-5. Epub ahead of print. PMID: 34650205.

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

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

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

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

Risk of lead exposure, subcortical brain structure, and cognition in a large cohort of 9- to 10-year-old children

Marshall AT, McConnell R, Lanphear BP, Thompson WK, Herting MM, Sowell ER. Risk of lead exposure, subcortical brain structure, and cognition in a large cohort of 9- to 10-year-old children. PLoS One. 2021 Oct 14;16(10):e0258469. doi: 10.1371/journal.pone.0258469. PMID: 34648580.

Adolescent civic engagement: Lessons from Black Lives Matter

Baskin-Sommers A, Simmons C, Conley M, Chang SA, Estrada S, Collins M, Pelham W, Beckford E Mitchell-Adams H, Berrian N, Tapert SF, Gee DG, Casey BJ. Adolescent civic engagement: Lessons from Black Lives Matter. PNAS October 12, 2021 118 (41) e2109860118; https://doi.org/10.1073/pnas.2109860118.

In 2020, individuals of all ages engaged in demonstrations condemning police brutality and supporting the Black Lives Matter (BLM) movement. Research that used parent reports and trends commented on in popular media suggested that adolescents under 18 had become increasingly involved in this movement. In the first large-scale quantitative survey of adolescents’ exposure to BLM demonstrations, 4,970 youth (meanage = 12.88 y) across the United States highlighted that they were highly engaged, particularly with media, and experienced positive emotions when exposed to the BLM movement. In addition to reporting strong engagement and positive emotions related to BLM demonstrations, Black adolescents in particular reported higher negative emotions when engaging with different types of media and more exposure to violence during in-person BLM demonstrations. Appreciating youth civic engagement, while also providing support for processing complex experiences and feelings, is important for the health and welfare of young people and society.

A Comprehensive Overview of the Physical Health of the Adolescent Brain Cognitive Development Study Cohort at Baseline

Palmer CE, Sheth C, Marshall AT, Adise S, Baker FC, Chang L, Clark DB, Coronado C, Dagher RK, Diaz V, Dowling GJ, Gonzalez MR, Haist F, Herting MM, Huber RS, Jernigan TL, LeBlanc K, Lee K, Lisdahl KM, Neigh G, Patterson MW, Renshaw P, Rhee KE, Tapert S, Thompson WK, Uban K, Sowell ER, Yurgelun-Todd D. A Comprehensive Overview of the Physical Health of the Adolescent Brain Cognitive Development Study Cohort at Baseline. Front Pediatr. 2021 Oct 5;9:734184. doi: 10.3389/fped.2021.734184. PMID: 34692610; PMCID: PMC8526338.

Physical health in childhood is crucial for neurobiological as well as overall development, and can shape long-term outcomes into adulthood. The landmark, longitudinal Adolescent Brain Cognitive Development StudySM (ABCD study®), was designed to investigate brain development and health in almost 12,000 youth who were recruited when they were 9-10 years old and will be followed through adolescence and early adulthood. The overall goal of this paper is to provide descriptive analyses of physical health measures in the ABCD study at baseline, including but not limited to sleep, physical activity and sports involvement, and body mass index. Further this summary will describe how physical health measures collected from the ABCD cohort compare with current normative data and clinical guidelines. We propose this data set has the potential to facilitate clinical recommendations and inform national standards of physical health in this age group. This manuscript will also provide important information for ABCD users and help guide analyses investigating physical health including new avenues for health disparity research as it pertains to adolescent and young adult development.

Recalibrating expectations about effect size: A multi-method survey of effect sizes in the ABCD study

Owens MM, Potter A, Hyatt CS, Albaugh M, Thompson WK, Jernigan T, Yuan D, Hahn S, Allgaier N, Garavan H. Recalibrating expectations about effect size: A multi-method survey of effect sizes in the ABCD study. PLoS One. 2021 Sep 23;16(9):e0257535. doi: 10.1371/journal.pone.0257535. PMID: 34555056.

Effect sizes are commonly interpreted using heuristics established by Cohen (e.g., small: r = .1, medium r = .3, large r = .5), despite mounting evidence that these guidelines are mis-calibrated to the effects typically found in psychological research. This study’s aims were to 1) describe the distribution of effect sizes across multiple instruments, 2) consider factors qualifying the effect size distribution, and 3) identify examples as benchmarks for various effect sizes. For aim one, effect size distributions were illustrated from a large, diverse sample of 9/10-year-old children. This was done by conducting Pearson’s correlations among 161 variables representing constructs from all questionnaires and tasks from the Adolescent Brain and Cognitive Development Study® baseline data. To achieve aim two, factors qualifying this distribution were tested by comparing the distributions of effect size among various modifications of the aim one analyses. These modified analytic strategies included comparisons of effect size distributions for different types of variables, for analyses using statistical thresholds, and for analyses using several covariate strategies. In aim one analyses, the median in-sample effect size was .03, and values at the first and third quartiles were .01 and .07. In aim two analyses, effects were smaller for associations across instruments, content domains, and reporters, as well as when covarying for sociodemographic factors. Effect sizes were larger when thresholding for statistical significance. In analyses intended to mimic conditions used in «real-world» analysis of ABCD data, the median in-sample effect size was .05, and values at the first and third quartiles were .03 and .09. To achieve aim three, examples for varying effect sizes are reported from the ABCD dataset as benchmarks for future work in the dataset. In summary, this report finds that empirically determined effect sizes from a notably large dataset are smaller than would be expected based on existing heuristics.

Covariate Correcting Networks for Identifying Associations Between Socioeconomic Factors and Brain Outcomes in Children

Cho H., Park G., Isaiah A., Kim W.H. (2021) Covariate Correcting Networks for Identifying Associations Between Socioeconomic Factors and Brain Outcomes in Children. In: de Bruijne M. et al. (eds) Medical Image Computing and Computer Assisted Intervention – MICCAI 2021. MICCAI 2021. Lecture Notes in Computer Science, vol 12907. Springer, Cham. https://doi.org/10.1007/978-3-030-87234-2_40

Brain development in adolescence is synthetically influenced by various factors such as age, education, and socioeconomic conditions. To identify an independent effect from a variable of interest (e.g., socioeconomic conditions), statistical models such as General Linear Model (GLM) are typically adopted to account for covariates (e.g., age and gender). However, statistical models may be vulnerable with insufficient sample size and outliers, and multiple tests for a whole brain analysis lead to inevitable false-positives without sufficient sensitivity. Hence, it is necessary to develop a unified framework for multiple tests that robustly fits the observation and increases sensitivity. We therefore propose a unified flexible neural network that optimizes on the contribution from the main variable of interest as introduced in original GLM, which leads to improved statistical outcomes. The results on group analysis with fractional anisotropy (FA) from Diffusion Tensor Images from Adolescent Brain Cognitive Development (ABCD) study demonstrate that the proposed method provides much more selective and meaningful detection of ROIs related to socioeconomic status over conventional methods.

Prevalence and correlates of suicidal ideation and suicide attempts in preadolescent children: A US population-based study

Lawrence HR, Burke TA, Sheehan AE, Pastro B, Levin RY, Walsh RFL, Bettis AH, Liu RT. Prevalence and correlates of suicidal ideation and suicide attempts in preadolescent children: A US population-based study. Transl Psychiatry 11, 489 (2021). https://doi.org/10.1038/s41398-021-01593-3.

The present study evaluated sociodemographic and diagnostic predictors of suicidal ideation and attempts in a nationally representative sample of preadolescent youth enrolled in the Adolescent Brain Cognitive Development Study. Rates and predictors of psychiatric treatment utilization among suicidal youth also were examined. Eleven thousand eight hundred and seventy-five 9- and 10-year-old children residing in the United States were assessed. Children and their parents/guardians provided reports of children’s lifetime history of suicidal ideation, suicide attempts, and psychiatric disorders. Parents also reported on sociodemographic characteristics and mental health service utilization. Multivariate logistic regression analyses were employed to evaluate sociodemographic and diagnostic correlates of suicidal ideation, suicide attempts among youth with suicidal ideation, and treatment utilization among youth with suicidal ideation and suicide attempts. Lifetime prevalence rates were 14.33% for suicidal ideation and 1.26% for suicide attempts. Youth who identified as male, a sexual minority, or multiracial had greater odds of suicidal ideation, and sexual minority youth and youth with a low family income had greater odds of suicide attempts. Comorbid psychopathology was associated with higher odds of both suicidal ideation and suicide attempts. In youth, 34.59% who have suicidal ideation and 54.82% who had attempted suicide received psychiatric treatment. Treatment utilization among suicidal youth was lower among those who identified as female, Black, and Hispanic. Suicidal ideation and attempts among preadolescent children are concerningly high and targeted assessment and preventative efforts are needed, especially for males, racial, ethnic, and sexual minority youth, and those youth experiencing comorbidity.

Vertex-wise multivariate genome-wide association study identifies 780 unique genetic loci associated with cortical morphology

Shadrin AA, Kaufmann T, van der Meer D, Palmer CE, Makowski C, Loughnan R, Jernigan TL, Seibert TM, Hagler DJ, Smeland OB, Motazedi E, Chu Y, Lin A, Cheng W, Hindley G, Thompson WK, Fan CC, Holland D, Westlye LT, Frei O, Andreassen OA, Dale AM. Vertex-wise multivariate genome-wide association study identifies 780 unique genetic loci associated with cortical morphology. Neuroimage. 2021 Sep 21;244:118603. doi: 10.1016/j.neuroimage.2021.118603. Epub ahead of print. PMID: 34560273.

Brain morphology has been shown to be highly heritable, yet only a small portion of the heritability is explained by the genetic variants discovered so far. Here we extended the Multivariate Omnibus Statistical Test (MOSTest) and applied it to genome-wide association studies (GWAS) of vertex-wise structural magnetic resonance imaging (MRI) cortical measures from N=35,657 participants in the UK Biobank. We identified 695 loci for cortical surface area and 539 for cortical thickness, in total 780 unique genetic loci associated with cortical morphology robustly replicated in 8,060 children of mixed ethnicity from the Adolescent Brain Cognitive Development (ABCD) Study®. This reflects more than 8-fold increase in genetic discovery at no cost to generalizability compared to the commonly used univariate GWAS methods applied to region of interest (ROI) data. Functional follow up including gene-based analyses implicated 10% of all protein-coding genes and pointed towards pathways involved in neurogenesis and cell differentiation. Power analysis indicated that applying the MOSTest to vertex-wise structural MRI data triples the effective sample size compared to conventional univariate GWAS approaches. The large boost in power obtained with the vertex-wise MOSTest together with pronounced replication rates and highlighted biologically meaningful pathways underscores the advantage of multivariate approaches in the context of highly distributed polygenic architecture of the human brain.

Identifying profiles of brain structure and associations with current and future psychopathology in youth

Mattoni M, Wilson S, Olino T. Identifying profiles of brain structure and associations with current and future psychopathology in youth. Developmental Cognitive Neuroscience, Volume 51, October 2021, 101013, https://doi.org/10.1016/j.dcn.2021.101013.

Brain structure is often studied as a marker of youth psychopathology by examining associations between volume or thickness of individual regions and specific diagnoses. However, these univariate approaches do not address whether the effect of a particular region may depend on the structure of other regions. Here, we identified subgroups of individuals with distinct profiles of brain structure and examined how these profiles were associated with concurrent and future youth psychopathology. We used latent profile analysis to identify distinct neuroanatomical profiles of subcortical region volume and orbitofrontal cortical thickness in the ABCD study (N = 9376, mean age = 9.91, SD = 0.62). We identified a five-profile solution consisting of a reduced subcortical volume profile, a reduced orbitofrontal thickness profile, a reduced limbic and elevated striatal volume profile, an elevated orbitofrontal thickness and reduced striatal volume profile, and an elevated orbitofrontal thickness and subcortical volume profile. While controlling for age, sex, and intracranial volume, profiles exhibited differences in concurrent psychopathology measured dimensionally and categorically and in psychopathology at 1-year follow-up measured dimensionally. Results show that profiles of brain structure have incremental validity for associations with youth psychopathology beyond intracranial volume.

Sleep Disturbances, Obesity, and Cognitive Function in Childhood: A Mediation Analysis

Mattey-Mora PP, Nelson EJ. Sleep Disturbances, Obesity, and Cognitive Function in Childhood: A Mediation Analysis. Curr Dev Nutr. 2021 Sep 15;5(10):nzab119. doi: 10.1093/cdn/nzab119. PMID: 34661044; PMCID: PMC8513758.

Background: Childhood cognitive development is influenced by biological and environmental factors. One such factor, obesity, impairs cognitive development and is associated with sleep disturbances.

Objectives: We aimed to examine the mediating role of sleep disturbances on the relation between BMI and cognitive function in children.

Methods: A total of 9951 children aged 9-10 y were included in this cross-sectional study. Children were recruited from the longitudinal ABCD (Adolescent Brain Cognitive Development) Study. Cognitive development was assessed using metrics for fluid, crystallized, and total cognitive function. Mediation analyses were conducted via linear regression modeling, with adjustment for potential confounders (sex, age, ethnicity, household income, parental education, and self-reported physical activity) for each of the 3 outcomes. Mediation significance was determined by bootstrapping.

Results: A statistically significant inverse association was found between BMI and total (β = -0.41, P < 0.001) and fluid (β = -0.49, P < 0.001) cognition, but not for crystallized cognition. Total sleep disturbances partially mediated the association between BMI and fluid cognition (indirect effect: -0.02, P = 0.002; proportion of the total effect: 0.05, P = 0.002), but no mediation was found in the association between BMI and total cognition.

Conclusions: Sleep disturbances partially mediate the effect of childhood obesity on cognitive function, particularly in fluid cognitions. Future work is necessary to understand the effects of sleep disturbances and obesity on reduced childhood cognition throughout time, predominantly across the life course.

Multimodal MR Images-Based Diagnosis of Early Adolescent Attention-Deficit/Hyperactivity Disorder Using Multiple Kernel Learning

Zhou X, Lin Q, Gui Y, Wang Z, Liu M, Lu H. Multimodal MR Images-Based Diagnosis of Early Adolescent Attention-Deficit/Hyperactivity Disorder Using Multiple Kernel Learning. Front Neurosci. 2021 Sep 14;15:710133. doi: 10.3389/fnins.2021.710133. PMID: 34594183; PMCID: PMC8477011.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common brain diseases among children. The current criteria of ADHD diagnosis mainly depend on behavior analysis, which is subjective and inconsistent, especially for children. The development of neuroimaging technologies, such as magnetic resonance imaging (MRI), drives the discovery of brain abnormalities in structure and function by analyzing multimodal neuroimages for computer-aided diagnosis of brain diseases. This paper proposes a multimodal machine learning framework that combines the Boruta based feature selection and Multiple Kernel Learning (MKL) to integrate the multimodal features of structural and functional MRIs and Diffusion Tensor Images (DTI) for the diagnosis of early adolescent ADHD. The rich and complementary information of the macrostructural features, microstructural properties, and functional connectivities are integrated at the kernel level, followed by a support vector machine classifier for discriminating ADHD from healthy children. Our experiments were conducted on the comorbidity-free ADHD subjects and covariable-matched healthy children aged 9-10 chosen from the Adolescent Brain and Cognitive Development (ABCD) study. This paper is the first work to combine structural and functional MRIs with DTI for early adolescents of the ABCD study. The results indicate that the kernel-level fusion of multimodal features achieves 0.698 of AUC (area under the receiver operating characteristic curves) and 64.3% of classification accuracy for ADHD diagnosis, showing a significant improvement over the early feature fusion and unimodal features. The abnormal functional connectivity predictors, involving default mode network, attention network, auditory network, and sensorimotor mouth network, thalamus, and cerebellum, as well as the anatomical regions in basal ganglia, are found to encode the most discriminative information, which collaborates with macrostructure and diffusion alterations to boost the performances of disorder diagnosis.

Genetic variation in endocannabinoid signaling is associated with differential network-level functional connectivity in youth

Sisk LM, Rapuano KM, Conley MI, Greene AS, Horien C, Rosenberg MD, Scheinost D, Constable RT, Glatt CE, Casey BJ, Gee DG. Genetic variation in endocannabinoid signaling is associated with differential network-level functional connectivity in youth. J Neurosci Res. 2021 Sep 8. doi: 10.1002/jnr.24946. Epub ahead of print. PMID: 34496065.

The endocannabinoid system is an important regulator of emotional responses such as fear, and a number of studies have implicated endocannabinoid signaling in anxiety. The fatty acid amide hydrolase (FAAH) C385A polymorphism, which is associated with enhanced endocannabinoid signaling in the brain, has been identified across species as a potential protective factor from anxiety. In particular, adults with the variant FAAH 385A allele have greater fronto-amygdala connectivity and lower anxiety symptoms. Whether broader network-level differences in connectivity exist, and when during development this neural phenotype emerges, remains unknown and represents an important next step in understanding how the FAAH C385A polymorphism impacts neurodevelopment and risk for anxiety disorders. Here, we leveraged data from 3,109 participants in the nationwide Adolescent Brain Cognitive Development Study℠ (10.04 ± 0.62 years old; 44.23% female, 55.77% male) and a cross-validated, data-driven approach to examine associations between genetic variation and large-scale resting-state brain networks. Our findings revealed a distributed brain network, comprising functional connections that were both significantly greater (95% CI for p values = [<0.001, <0.001]) and lesser (95% CI for p values = [0.006, <0.001]) in A-allele carriers relative to non-carriers. Furthermore, there was a significant interaction between genotype and the summarized connectivity of functional connections that were greater in A-allele carriers, such that non-carriers with connectivity more similar to A-allele carriers (i.e., greater connectivity) had lower anxiety symptoms (β = -0.041, p = 0.030). These findings provide novel evidence of network-level changes in neural connectivity associated with genetic variation in endocannabinoid signaling and suggest that genotype-associated neural differences may emerge at a younger age than genotype-associated differences in anxiety.