Scientific Publications

Trompeter N, Testa A, Raney JH, Jackson DB, Al-Shoaibi AAA, Ganson KT, Shao IY, Nagata JM. The Association Between Adverse Childhood Experiences (ACEs), Bullying Victimization, and Internalizing and Externalizing Problems Among Early Adolescents: Examining Cumulative and Interactive Associations. J Youth Adolesc. 2023 Dec 8. doi: 10.1007/s10964-023-01907-2. Epub ahead of print. PMID: 38066316.

Both adverse childhood experiences (ACEs) and bullying victimization are linked with mental health problems in adolescents. However, little is known about the overlap between the two factors and how this impacts adolescent mental health problems (i.e., internalizing and externalizing problems). The current study analyzed data from 8,085 participants (47.7% female; 44.1% racial/ethnic minority) in the Adolescent Brain Cognitive Development (ABCD) study, baseline (2016-2018, ages 9-10 years) to Year 2. Regression analyses were used to estimate associations between ACEs, bullying victimization and mental health problems, respectively, adjusting for sex, race/ethnicity, country of birth, household income, parental education, and study site. The findings showed that both ACEs and bullying victimization were independently associated with higher internalizing and higher externalizing problems. However, no significant interaction was found between ACEs and bullying victimization. Overall, the results align with the cumulative risk model of adversity, linking cumulative ACEs and bullying victimization to internalizing and externalizing problems in early adolescents.

Yan W, Fu Z, Jiang R, Sui J, Calhoun VD. Maximum Classifier Discrepancy Generative Adversarial Network for Jointly Harmonizing Scanner Effects and Improving Reproducibility of Downstream Tasks. IEEE Trans Biomed Eng. 2023 Dec 7;PP. doi: 10.1109/TBME.2023.3330087. Epub ahead of print. PMID: 38060365.

Objective: Multi-site collaboration is essential for overcoming small-sample problems when exploring reproducible biomarkers in MRI studies. However, various scanner-specific factors dramatically reduce the cross-scanner replicability. Moreover, existing harmony methods mostly could not guarantee the improved performance of downstream tasks.

Methods: we proposed a new multi-scanner harmony framework, called ‘maximum classifier discrepancy generative adversarial network’, or MCD-GAN, for removing scanner effects in the original feature space while preserving substantial biological information for downstream tasks. Specifically, the adversarial generative network was utilized for persisting the structural layout of each sample, and the maximum classifier discrepancy module was introduced for regulating GAN generators by incorporating the downstream tasks.

Results: We compared the MCD-GAN with other state-of-the-art data harmony approaches (e.g., ComBat, CycleGAN) on simulated data and the Adolescent Brain Cognitive Development (ABCD) dataset. Results demonstrate that MCD-GAN outperformed other approaches in improving cross-scanner classification performance while preserving the anatomical layout of the original images.

Significance: To the best of our knowledge, the proposed MCD-GAN is the first generative model which incorporates downstream tasks while harmonizing, and is a promising solution for facilitating cross-site reproducibility in various tasks such as classification and regression. The codes of the MCD-GAN are available at https://github.com/trendscenter/MCD-GAN.

Wang Y, Zhao W, Ross A, You L, Wang H, Zhou X. Revealing chronic disease progression patterns using Gaussian process for stage inference. J Am Med Inform Assoc. 2023 Dec 5:ocad230. doi: 10.1093/jamia/ocad230. Epub ahead of print. PMID: 38055638.

Objective: The early stages of chronic disease typically progress slowly, so symptoms are usually only noticed until the disease is advanced. Slow progression and heterogeneous manifestations make it challenging to model the transition from normal to disease status. As patient conditions are only observed at discrete timestamps with varying intervals, an incomplete understanding of disease progression and heterogeneity affects clinical practice and drug development.

Materials and methods: We developed the Gaussian Process for Stage Inference (GPSI) approach to uncover chronic disease progression patterns and assess the dynamic contribution of clinical features. We tested the ability of the GPSI to reliably stratify synthetic and real-world data for osteoarthritis (OA) in the Osteoarthritis Initiative (OAI), bipolar disorder (BP) in the Adolescent Brain Cognitive Development Study (ABCD), and hepatocellular carcinoma (HCC) in the UTHealth and The Cancer Genome Atlas (TCGA).

Results: First, GPSI identified two subgroups of OA based on image features, where these subgroups corresponded to different genotypes, indicating the bone-remodeling and overweight-related pathways. Second, GPSI differentiated BP into two distinct developmental patterns and defined the contribution of specific brain region atrophy from early to advanced disease stages, demonstrating the ability of the GPSI to identify diagnostic subgroups. Third, HCC progression patterns were well reproduced in the two independent UTHealth and TCGA datasets.

Conclusion: Our study demonstrated that an unsupervised approach can disentangle temporal and phenotypic heterogeneity and identify population subgroups with common patterns of disease progression. Based on the differences in these features across stages, physicians can better tailor treatment plans and medications to individual patients.

Dehestani, N., Vijayakumar, N., Ball, G. et al. “Puberty age gap”: new method of assessing pubertal timing and its association with mental health problems. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-02316-4

Puberty is linked to mental health problems during adolescence, and in particular, the timing of puberty is thought to be an important risk factor. This study developed a new measure of pubertal timing that was built upon multiple pubertal features and their nonlinear changes over time (i.e., with age), and investigated its association with mental health problems. Using the Adolescent Brain Cognitive Development (ABCD) cohort (N ~ 9900, aged 9–13 years), we employed three different models to assess pubertal timing. These models aimed to predict chronological age based on: (i) observed physical development, (ii) hormone levels (testosterone and dehydroepiandrosterone [DHEA]), and (iii) a combination of both physical development and hormones. To achieve this, we utilized a supervised machine learning approach, which allowed us to train the models using the available data and make age predictions based on the input pubertal features. The accuracy of these three models was evaluated, and their associations with mental health problems were examined. The new pubertal timing model performed better at capturing age variance compared to the more commonly used linear regression method. Further, the model based on physical features accounted for the most variance in mental health, such that earlier pubertal timing was associated with higher symptoms. This study demonstrates the utility of our new model of pubertal timing and suggests that, relative to hormonal measures, physical measures of pubertal maturation have a stronger association with mental health problems in early adolescence.

Wade NE, Wallace AL, Huestis MA, et al. Cannabis Use and Neurocognitive Performance at 13-14 Years-Old: Optimizing Assessment with Hair Toxicology in the Adolescent Brain Cognitive Development (ABCD) Study. Addictive Behaviors. Available online 2 December 2023, 107930, In Press, Journal Pre-proof. https://doi.org/10.1016/j.addbeh.2023.107930

Objective
Cannabis is widely used, including in early adolescence, with prevalence rates varying by measurement method (e.g., toxicology vs. self-report). Critical neurocognitive development occurs throughout adolescence. Given conflicting prior brain-behavior results in cannabis research, improved measurement of cannabis use in younger adolescents is needed.

Methods
Data from the Adolescent Brain Cognitive Development (ABCD) Study Year 4 follow-up (participant age: 13-14 years-old) included hair samples assessed by LC-MS/MS and GC-MS/MS, quantifying THCCOOH (THC metabolite), THC, and cannabidiol concentrations, and the NIH Toolbox Cognitive Battery. Youth whose hair was positive for cannabinoids or reported past-year cannabis use were included in a Cannabis Use (CU) group (n=123) and matched with non-using Controls on sociodemographics (n=123). Standard and nested ANCOVAs assessed group status predicting cognitive performance, controlling for family relationships. Follow-up correlations assessed cannabinoid hair concentration, self-reported cannabis use, and neurocognition.

Results
CU scored lower on Picture Memory (p=.03) than Controls. Within the CU group, THCCOOH negatively correlated with Picture Vocabulary (r=-0.20, p=.03) and Flanker Inhibitory Control and Attention (r=-0.19, p=.04), and past-year cannabis use was negatively associated with List Sorting Working Memory (r=-0.33, p=.0002) and Picture Sequence Memory (r=-0.19, p=.04) performances.

Conclusions
Youth who had used cannabis showed lower scores on an episodic memory task, and more cannabis use was linked to poorer performances on verbal, inhibitory, working memory, and episodic memory tasks. Combining hair toxicology with self-report revealed more brain-behavior relationships than self-report data alone. These youth will be followed to determine long-term substance use and neurocognition trajectories.

Shao IY, Al-Shoaibi AAA, Testa A, Ganson KT, Baker FC, Nagata JM. The Association between Family Environment and Subsequent Risk of Cyberbullying Victimization in Adolescents. Acad Pediatr. 2023 Nov 30:S1876-2859(23)00423-0. doi: 10.1016/j.acap.2023.11.019. Epub ahead of print. PMID: 38042404.

Background: Family environment and parental monitoring have long been recognized as two important factors associated with adolescents’ psychological development. Studies have suggested a potential link between parenting style/parental engagement and the likelihood of bullying victimization among adolescents. Nonetheless, no studies to date have investigated the association between family environment and the subsequent risk of cyberbullying victimization among adolescents. In this study, we assessed the association between family environment (e.g. parental monitoring and family conflict) and subsequent risk of cyberbullying victimization using data from the Adolescent Brain Cognitive Development (ABCD).

Methods: We used multivariable logistic regressions to assess the association between parental monitoring and family conflict at year 1 and the subsequent risk of cyberbullying victimization at year 2 in 10,410 eligible ABCD study participants.

Results: Adjusting for sociodemographic characteristics, study sampling weights and study site, higher levels of parental monitoring at year 1 were associated with a lower reported past 12-month (OR:0.61, 95% CI: 0.50 – 0.75) history of cyberbullying victimization at year 2. Higher levels of family conflict at year 1 were associated with a higher risk of reported past 12-month history (OR:1.13, 95% CI: 1.09-1.18) of cyberbullying victimization one year later.

Conclusion: Higher levels of parental monitoring and lower levels of family conflict are associated with a subsequent lower risk of cyberbullying victimization among adolescents. Cyberbullying victimization preventive programs should advocate for increased parental monitoring and minimize family conflict at home to reduce the risks of cyberbullying victimization among adolescents.

van Rooij SJH, Powers A. Maternal Stress and Vulnerability in Offspring: Hippocampal Mechanisms of Resilience. Biol Psychiatry. 2024 Jan 1;95(1):3-5. doi: 10.1016/j.biopsych.2023.10.004. PMID: 38030307.

Brown SA, Jernigan TL, Dowling GJ. The adolescent brain cognitive development study. Health Psychol. 2023 Dec;42(12):840-841. doi: 10.1037/hea0001353. PMID: 38032600.

The Adolescent Brain Cognitive Development (ABCD) Study was launched by the Collaborative Research on Addiction at NIH (CRAN) in 2016 and is now supported by 11 other federal agencies and centers. The six primary aims of ABCD were to: Develop national standards for normal brain development for youth ages 9-19 years; Determine individual developmental trajectories (e.g., brain, cognitive, and emotional development, academic progress), and identify factors that can influence (protectively or adversely) these developmental patterns; Examine the roles of genetic, cultural, and environmental factors in youth development, as well as their interactions; Evaluate the effects of health, physical activity, sleep, social activities, sports injuries, and other experiences on brain and developmental outcomes; Assess the onset and progression of mental health (MH) disorders and factors that influence their course and severity as well as the relations between MH and substance use (SU); Determine how substance exposure patterns affect developmental outcomes, including brain development, and vice versa. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Freedland KE, Ruiz JM. Adolescent health behavior research. Health Psychol. 2023 Dec;42(12):839. doi: 10.1037/hea0001314. PMID: 38032599.

The Adolescent Brain Cognitive Development (ABCD) Study is the largest, long-term study of brain development and child and adolescent health that has ever been conducted in the United States. The ABCD Research Consortium is supported by the National Institutes of Health and includes a central coordinating center, a data analysis and informatics core, and 21 research sites across the country. This special issue of Health Psychology presents some important findings on adolescent health behavior that have recently emerged from the ABCD Study (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Sanchez M, Feldstein Ewing SW, Luciana M. Leveraging the adolescent brain cognitive development study to advance and promote adolescent health: Introduction to the special issue. Health Psychol. 2023 Dec;42(12):835-838. doi: 10.1037/hea0001351. PMID: 38032598.

The empirical reports in this special issue of Health Psychology showcase the work of a diverse array of accomplished early-stage investigators who are members of the Adolescent Brain Cognitive Development (ABCD) study consortium and who are drawn from the community of female and underrepresented scientists. Their studies focus primarily on youth assessed during preadolescence and early adolescence, and they are based on the ABCD data that were available to the scientific community at the time this special issue was being prepared (e.g., baseline, Years 1 and 2 assessments). They address a variety of questions about adolescent health behavior, such as the effects of screen time and caffeine on sleep; individual lifestyle, neighborhood, and environmental factors associated with physical health conditions and brain development; and the antecedents and consequences of prenatal and adolescent substance exposure. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Hu L, Katz ES, Stamoulis C. Modulatory effects of fMRI acquisition time of day, week and year on adolescent functional connectomes across spatial scales: Implications for inference. NeuroImage, Volume 284, 15 December 2023, 120459. https://doi.org/10.1016/j.neuroimage.2023.120459

Metabolic, hormonal, autonomic and physiological rhythms may have a significant impact on cerebral hemodynamics and intrinsic brain synchronization measured with fMRI (the resting-state connectome). The impact of their characteristic time scales (hourly, circadian, seasonal), and consequently scan timing effects, on brain topology in inherently heterogeneous developing connectomes remains elusive. In a cohort of 4102 early adolescents with resting-state fMRI (median age = 120.0 months; 53.1 % females) from the Adolescent Brain Cognitive Development Study, this study investigated associations between scan time-of-day, time-of-week (school day vs weekend) and time-of-year (school year vs summer vacation) and topological properties of resting-state connectomes at multiple spatial scales. On average, participants were scanned around 2 pm, primarily during school days (60.9 %), and during the school year (74.6 %). Scan time-of-day was negatively correlated with multiple whole-brain, network-specific and regional topological properties (with the exception of a positive correlation with modularity), primarily of visual, dorsal attention, salience, frontoparietal control networks, and the basal ganglia. Being scanned during the weekend (vs a school day) was correlated with topological differences in the hippocampus and temporoparietal networks. Being scanned during the summer vacation (vs the school year) was consistently positively associated with multiple topological properties of bilateral visual, and to a lesser extent somatomotor, dorsal attention and temporoparietal networks. Time parameter interactions suggested that being scanned during the weekend and summer vacation enhanced the positive effects of being scanned in the morning. Time-of-day effects were overall small but spatially extensive, and time-of-week and time-of-year effects varied from small to large (Cohen’s f ≤ 0.1, Cohen’s d<0.82, p < 0.05). Together, these parameters were also positively correlated with temporal fMRI signal variability but only in the left hemisphere. Finally, confounding effects of scan time parameters on relationships between connectome properties and cognitive task performance were assessed using the ABCD neurocognitive battery. Although most relationships were unaffected by scan time parameters, their combined inclusion eliminated associations between properties of visual and somatomotor networks and performance in the Matrix Reasoning and Pattern Comparison Processing Speed tasks. Thus, scan time of day, week and year may impact measurements of adolescent brain’s functional circuits, and should be accounted for in studies on their associations with cognitive performance, in order to reduce the probability of incorrect inference.

Barton AW, Yu T, Gong Q, Chen E, Miller GE, Brody GH. Skin-deep Resilience and Early Adolescence: Neighborhood Disadvantage, Executive Functioning, and Pubertal Development in Minority Youth. J Youth Adolesc. 2023 Nov 28. doi: 10.1007/s10964-023-01911-6. Epub ahead of print. PMID: 38015355.

Skin-deep resilience, in which youth overcome adversity and achieve success in psychological and academic domains but at a cost to their physiological well-being, has been documented in late adolescence and adulthood. However, its potential to emerge at earlier developmental stages is unknown. To address this gap, secondary data analyses were executed using waves 1 and 2 of the Adolescent Brain Cognitive Development study (n = 7712; ages 9-10 years at baseline [mean: 9.92; SD = 0.63]; 47.1% female; 66.1% White, 13.4% Black, and 20.6% Hispanic). The results indicated high levels of executive functioning were associated with improved psychological and behavioral outcomes at one-year follow-up. However, for racial and ethnic minority (i.e., Black or Hispanic) youth from disadvantaged neighborhoods, high levels of executive functioning were also associated with accelerated pubertal development. No significant interaction was observed among White youth. The findings suggest the skin-deep resilience pattern may be evident in early adolescence.

Smith C, Stamoulis C. Effects of multidomain environmental and mental health factors on the development of empathetic behaviors and emotions in adolescence. PLoS One. 2023 Nov 22;18(11):e0293473. doi: 10.1371/journal.pone.0293473. PMID: 37992006; PMCID: PMC10664943.

Empathy is at the core of our social world, yet multidomain factors that affect its development in socially sensitive periods, such as adolescence, are incompletely understood. To address this gap, this study investigated associations between social, environmental and mental health factors, and their temporal changes, on adolescent empathetic behaviors/emotions and, for comparison, callous unemotional (CU) traits and behaviors, in the early longitudinal Adolescent Brain Cognitive Development sample (baseline: n = 11062; 2-year follow-up: n = 9832, median age = 119 and 144 months, respectively). Caregiver affection towards the youth, liking school, having a close friend, and importance of religious beliefs/spirituality in the youth’s life were consistently positively correlated with empathetic behaviors/emotions across assessments (p<0.001, Cohen’s f = ~0.10). Positive family dynamics and cohesion, living in a neighborhood that shared the family’s values, but also parent history of substance use and (aggregated) internalizing problems were additionally positively associated with one or more empathetic behaviors at follow-up (p<0.001, f = ~0.10). In contrast, externalizing problems, anxiety, depression, fear of social situations, and being withdrawn were negatively associated with empathetic behaviors and positively associated with CU traits and behaviors (p<0.001, f = ~0.1-0.44). The latter were also correlated with being cyberbullied and/or discriminated against, anhedonia, and impulsivity, and their interactions with externalizing and internalizing issues. Significant positive temporal correlations of behaviors at the two assessments indicated positive (early) developmental empathetic behavior trajectories, and negative CU traits’ trajectories. Negative changes in mental health adversely moderated positive trajectories and facilitated negative ones. These findings highlight that adolescent empathetic behaviors/emotions are positively related to multidomain protective social environmental factors, but simultaneously adversely associated with risk factors in the same domains, as well as bully victimization, discrimination, and mental health problems. Risk factors instead facilitate the development of CU traits and behaviors.

Kiss O, Qu Z, Müller-Oehring EM, et al. Sleep, brain systems, and persistent stress in early adolescents during COVID-19: Insights from the ABCD study. Journal of Affective Disorders. Volume 346, 1 February 2024, Pages 234-241. https://doi.org/10.1016/j.jad.2023.10.158.

Purpose
The first year of the COVID-19 pandemic constituted a major life stress event for many adolescents, associated with disrupted school, behaviors, social networks, and health concerns. However, pandemic-related stress was not equivalent for everyone and could have been influenced by pre-pandemic factors including brain structure and sleep, which both undergo substantial development during adolescence. Here, we analyzed clusters of perceived stress levels across the pandemic and determined developmentally relevant pre-pandemic risk factors in brain structure and sleep of persistently high stress during the first year of the COVID-19 pandemic.

Methods
We investigated longitudinal changes in perceived stress at six timepoints across the first year of the pandemic (May 2020–March 2021) in 5559 adolescents (50 % female; age range: 11–14 years) in the United States (U.S.) participating in the Adolescent Brain Cognitive Development (ABCD) study. In 3141 of these adolescents, we fitted machine learning models to identify the most important pre-pandemic predictors from structural MRI brain measures and self-reported sleep data that were associated with persistently high stress across the first year of the pandemic.

Results
Patterns of perceived stress levels varied across the pandemic, with 5 % reporting persistently high stress. Our classifiers accurately detected persistently high stress (AUC > 0.7). Pre-pandemic brain structure, specifically cortical volume in temporal regions, and cortical thickness in multiple parietal and occipital regions, predicted persistent stress. Pre-pandemic sleep difficulties and short sleep duration were also strong predictors of persistent stress, along with more advanced pubertal stage.

Conclusions
Adolescents showed variable stress responses during the first year of the COVID-19 pandemic, and some reported persistently high stress across the whole first year. Vulnerability to persistent stress was evident in several brain structural and self-reported sleep measures, collected before the pandemic, suggesting the relevance of other pre-existing individual factors beyond pandemic-related factors, for persistently high stress responses.

Kochvar A, Liu Y, Munafo M, Xu Z, Dai HD. Genetic and environmental influences on early-age susceptibility and initiation of nicotine-containing product use: A twin-pairs study. Tob Prev Cessat. 2023 Nov 21;9:34. doi: 10.18332/tpc/173556. PMID: 38026821; PMCID: PMC10660284.

Introduction: Nicotine-containing products (NCPs) such as electronic nicotine delivery systems (ENDS) are increasingly common throughout the landscape of youth use of nicotine-containing products (NCP), and have overtaken traditional cigarette smoking modalities. This study seeks to examine the genetic and environmental influences on liability for susceptibility and initiation of ENDS and other NCPs among US children.

Methods: Data were drawn from 886 monozygotic (MZ) and dizygotic (DZ) twin pairs aged 9-10 years in the Adolescent Brain & Cognitive Development (ABCD) study at the baseline during 2016-2018. Heritability (h2) measured the proportion of the total phenotypic variation attributable to genes. Variance component models were utilized to analyze influences from the common environment (c2) and unique environmental factors (e2), taking into account correlations within twin pairs.

Results: The national sample included 50% females, 69.5% of non-Hispanic Whites, 12.8% of non-Hispanic Blacks, and 11.6% of Hispanics, with a mean age of 121.5 months. The twin sets were 60% DZ and 40% MZ. Heritability was low for NCP susceptibility (h2=0) and moderate for NCP initiation (h2=39%, p=0.02). The variance associated with NCP susceptibility was primarily influenced by environmental factors, especially one’s unique factors (c2=37%, p<0.0001 vs e2=63%, p<0.0001). In contrast, the variance associated with NCP initiation was split across common and unique environmental factors (c2=32%, p=0.02 vs e2=29%, p=0.02).

Conclusions: In the era with ENDS use surging among youth, NCP initiation remains to be a heritable trait with joint influence from the environment. NCP susceptibility is largely influenced by environmental factors, especially unique environments. Continued assessment of gene × environment interaction can better inform future youth NCP interventions.

King EK, Halbreich ED, Callina K, Mueller MK. Companion animals and the relationship between peer victimization and emotion regulation in youth. J Res Adolesc. 2023 Nov 17. doi: 10.1111/jora.12901. Epub ahead of print. PMID: 37975498.

Peer victimization can negatively impact emotion regulation in youth and is associated with harmful mental health outcomes. One protective factor against the impacts of peer victimization is a strong attachment to family and positive peer relationships. Given that pets are commonly seen as family members and that youth report turning to their pet for emotional comfort, companion animals could provide an avenue of support for youth experiencing victimization. A geographically diverse sample of 5725 adolescents in the United States from the Adolescent Brain Cognitive Development (ABCD) Study® was used to explore whether the relationship between peer victimization and emotion regulation was moderated by whether a pet lives in the home. Having a pet in the home did not moderate the relationship between peer victimization and emotion regulation; however, mean-level differences were present across types of household pet (i.e., youth with no pets, youth with at least one dog, and youth with non-dog pets). Participants who did not live with a companion animal showed higher levels of both maladaptive emotion regulation (expressive suppression) and adaptive emotion regulation (cognitive reappraisal), suggesting that having a pet might lower overall emotion regulation pathways regardless of adaptive directionality. Relational victimization was a significant predictor of expressive suppression regardless of whether there was a pet in the home, although overt victimization was not a predictor of either kind of emotion regulation. This research demonstrates the complex nature of human-animal relationships and suggests more research is needed to understand the nuanced relationship between pets, peer victimization, and emotion regulation.

Goovaerts S, Hoskens H, Eller RJ, Herrick N, Musolf AM, Justice CM, Yuan M, Naqvi S, Lee MK, Vandermeulen D, Szabo-Rogers HL, Romitti PA, Boyadjiev SA, Marazita ML, Shaffer JR, Shriver MD, Wysocka J, Walsh S, Weinberg SM, Claes P. Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape. Nat Commun. 2023 Nov 16;14(1):7436. doi: 10.1038/s41467-023-43237-8. PMID: 37973980; PMCID: PMC10654897.

The cranial vault in humans is highly variable, clinically relevant, and heritable, yet its genetic architecture remains poorly understood. Here, we conduct a joint multi-ancestry and admixed multivariate genome-wide association study on 3D cranial vault shape extracted from magnetic resonance images of 6772 children from the ABCD study cohort yielding 30 genome-wide significant loci. Follow-up analyses indicate that these loci overlap with genomic risk loci for sagittal craniosynostosis, show elevated activity cranial neural crest cells, are enriched for processes related to skeletal development, and are shared with the face and brain. We present supporting evidence of regional localization for several of the identified genes based on expression patterns in the cranial vault bones of E15.5 mice. Overall, our study provides a comprehensive overview of the genetics underlying normal-range cranial vault shape and its relevance for understanding modern human craniofacial diversity and the etiology of congenital malformations.

Hu L, Katz ES, Stamoulis C. Modulatory effects of fMRI acquisition time of day, week and year on adolescent functional connectomes across spatial scales: Implications for inference. Neuroimage. 2023 Nov 15;284:120459. doi: 10.1016/j.neuroimage.2023.120459. Epub ahead of print. PMID: 37977408.

Metabolic, hormonal, autonomic and physiological rhythms may have a significant impact on cerebral hemodynamics and intrinsic brain synchronization measured with fMRI (the resting-state connectome). The impact of their characteristic time scales (hourly, circadian, seasonal), and consequently scan timing effects, on brain topology in inherently heterogeneous developing connectomes remains elusive. In a cohort of 4102 early adolescents with resting-state fMRI (median age = 120.0 months; 53.1 % females) from the Adolescent Brain Cognitive Development Study, this study investigated associations between scan time-of-day, time-of-week (school day vs weekend) and time-of-year (school year vs summer vacation) and topological properties of resting-state connectomes at multiple spatial scales. On average, participants were scanned around 2 pm, primarily during school days (60.9 %), and during the school year (74.6 %). Scan time-of-day was negatively correlated with multiple whole-brain, network-specific and regional topological properties (with the exception of a positive correlation with modularity), primarily of visual, dorsal attention, salience, frontoparietal control networks, and the basal ganglia. Being scanned during the weekend (vs a school day) was correlated with topological differences in the hippocampus and temporoparietal networks. Being scanned during the summer vacation (vs the school year) was consistently positively associated with multiple topological properties of bilateral visual, and to a lesser extent somatomotor, dorsal attention and temporoparietal networks. Time parameter interactions suggested that being scanned during the weekend and summer vacation enhanced the positive effects of being scanned in the morning. Time-of-day effects were overall small but spatially extensive, and time-of-week and time-of-year effects varied from small to large (Cohen’s f ≤ 0.1, Cohen’s d<0.82, p < 0.05). Together, these parameters were also positively correlated with temporal fMRI signal variability but only in the left hemisphere. Finally, confounding effects of scan time parameters on relationships between connectome properties and cognitive task performance were assessed using the ABCD neurocognitive battery. Although most relationships were unaffected by scan time parameters, their combined inclusion eliminated associations between properties of visual and somatomotor networks and performance in the Matrix Reasoning and Pattern Comparison Processing Speed tasks. Thus, scan time of day, week and year may impact measurements of adolescent brain’s functional circuits, and should be accounted for in studies on their associations with cognitive performance, in order to reduce the probability of incorrect inference.

Levin R, Liu R. Post-traumatic stress disorder in a national sample of preadolescent children: Prevalence, correlates, clinical sequelae, and treatment utilization. Res Sq [Preprint]. 2023 Nov 15:rs.3.rs-3303568. doi: 10.21203/rs.3.rs-3303568/v1. PMID: 38014240; PMCID: PMC10680942.

Although posttraumatic stress disorder (PTSD) has been well characterized in adults, its epidemiology in children is unclear. The current study provides the first population-based examination of the prevalence of PTSD, sociodemographic and psychiatric correlates, clinical sequelae, and associations with psychiatric treatment in preadolescents in the United States. Data from the Adolescent Brain and Cognitive Development (ABCD) Study (release 5.0) was analyzed. Participants (unweighted n = 11, 875) were recruited from 21 sites across the United States. Current and lifetime PTSD prevalence were estimated, as was treatment use among children with PTSD. Sociodemographic, psychiatric correlates and sequelae of PTSD were analyzed using logistic regression, as was the association between PTSD and psychiatric treatment. Lifetime prevalence of PTSD was 2.17%. Sexual minority status, being multiracial, having unmarried parents, and family economic insecurity were associated with greater odds of PTSD. Among psychiatric disorders, separation anxiety was most strongly associated with PTSD, although general comorbid psychopathology was associated with greater odds of PTSD. Prior history of PTSD predicted new onset of other psychiatric disorders after PTSD remission. Nearly one in three children with lifetime PTSD did not receive psychiatric treatment, despite negative long-term outcomes of PTSD and significant psychiatric comorbidity. Even among preadolescents who experience full remission of PTSD, significant risk for future psychiatric illness remains. Further, the current findings underscore the need for improved efforts to reduce unmet treatment needs among those with PTSD at this age.

Wang Y, Peng W, Tapert SF, Zhao Q, Pohl KM. Imputing Brain Measurements Across Data Sets via Graph Neural Networks. Predict Intell Med. 2023;14277:172-183. doi: 10.1007/978-3-031-46005-0_15. PMID: 37946742; PMCID: PMC10634632.

Publicly available data sets of structural MRIs might not contain specific measurements of brain Regions of Interests (ROIs) that are important for training machine learning models. For example, the curvature scores computed by Freesurfer are not released by the Adolescent Brain Cognitive Development (ABCD) Study. One can address this issue by simply reapplying Freesurfer to the data set. However, this approach is generally computationally and labor intensive (e.g., requiring quality control). An alternative is to impute the missing measurements via a deep learning approach. However, the state-of-the-art is designed to estimate randomly missing values rather than entire measurements. We therefore propose to re-frame the imputation problem as a prediction task on another (public) data set that contains the missing measurements and shares some ROI measurements with the data sets of interest. A deep learning model is then trained to predict the missing measurements from the shared ones and afterwards is applied to the other data sets. Our proposed algorithm models the dependencies between ROI measurements via a graph neural network (GNN) and accounts for demographic differences in brain measurements (e.g. sex) by feeding the graph encoding into a parallel architecture. The architecture simultaneously optimizes a graph decoder to impute values and a classifier in predicting demographic factors. We test the approach, called Demographic Aware Graph-based Imputation (DAGI), on imputing those missing Freesurfer measurements of ABCD (N=3760; minimum age 12 years) by training the predictor on those publicly released by the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA, N=540). 5-fold cross-validation on NCANDA reveals that the imputed scores are more accurate than those generated by linear regressors and deep learning models. Adding them also to a classifier trained in identifying sex results in higher accuracy than only using those Freesurfer scores provided by ABCD.

Michael C, Taxali A, Angstadt M, Kardan O, Weigard A, Molloy MF, McCurry KL, Hyde LW, Heitzeg MM, Sripada C. Socioeconomic resources in youth are linked to divergent patterns of network integration and segregation across the brain’s transmodal axis. bioRxiv [Preprint]. 2023 Nov 13:2023.11.08.565517. doi: 10.1101/2023.11.08.565517. PMID: 38014302; PMCID: PMC10680554.

Socioeconomic resources (SER) calibrate the developing brain to the current context, which can confer or attenuate risk for psychopathology across the lifespan. Recent multivariate work indicates that SER levels powerfully influence intrinsic functional connectivity patterns across the entire brain. Nevertheless, the neurobiological meaning of these widespread alterations remains poorly understood, despite its translational promise for early risk identification, targeted intervention, and policy reform. In the present study, we leverage the resources of graph theory to precisely characterize multivariate and univariate associations between household SER and the functional integration and segregation (i.e., participation coefficient, within-module degree) of brain regions across major cognitive, affective, and sensorimotor systems during the resting state in 5,821 youth (ages 9-10 years) from the Adolescent Brain Cognitive Development (ABCD) Study. First, we establish that decomposing the brain into profiles of integration and segregation captures more than half of the multivariate association between SER and functional connectivity with greater parsimony (100-fold reduction in number of features) and interpretability. Second, we show that the topological effects of SER are not uniform across the brain; rather, higher SER levels are related to greater integration of somatomotor and subcortical systems, but greater segregation of default mode, orbitofrontal, and cerebellar systems. Finally, we demonstrate that the effects of SER are spatially patterned along the unimodal-transmodal gradient of brain organization. These findings provide critical interpretive context for the established and widespread effects of SER on brain organization, indicating that SER levels differentially configure the intrinsic functional architecture of developing unimodal and transmodal systems. This study highlights both sensorimotor and higher-order networks that may serve as neural markers of environmental stress and opportunity, and which may guide efforts to scaffold healthy neurobehavioral development among disadvantaged communities of youth.

Martinez Agulleiro L, Castellanos FX, Janssen A, Baroni A. Family Discordance in Gender Identification Is Not Associated with Increased Depression and Anxiety Among Trans Youth. LGBT Health. 2023 Nov 8. doi: 10.1089/lgbt.2023.0143. Epub ahead of print. PMID: 37935035.

Purpose: We examined the relationship between parent- and child-reported gender identity of the youth with internalizing symptoms in transgender and gender-diverse (TGD) youth. In addition, we investigated differences in sex assigned at birth ratios and pubertal development stages in TGD and cisgender youth. Methods: We analyzed longitudinal data from the Adolescent Brain Cognitive Development study (ABCD), corresponding to baseline and 1st-to-3rd-year follow-up interviews (n = 6030 to n = 9743, age range [9-13]). Sociodemographic variables, self- and parent-reported gender identity, and clinical measures were collected. Results: TGD youth showed higher levels of internalizing symptoms compared with cisgender youth. However, this was not worsened by discordance in gender identification between TGD youth and parents. Over the 3-year follow-up period, the number of TGD participants increased from 0.8% (95% confidence interval (CI) [0.6-1.0]) at baseline to 1.4% (95% CI [1.1-1.7]) at the 3rd-year follow-up (χ2 = 10.476, df = 1, false discovery rate (FDR)-adjusted p = 0.00256), particularly among those assigned female at birth (AFAB) in relation to people assigned male at birth (AMAB) (AMAB:AFAB at baseline: 1:1.9 vs. AMAB:AFAB at 3rd-year follow-up: 1:4.7, χ2 = 40.357, df = 1, FDR-adjusted p < 0.0001). Conclusions: TGD youth in ABCD reported higher internalizing symptoms than cisgender youth, although this was not affected by parental discordance in gender identification. A substantial increase over time in TGD children AFAB was documented. More research is needed to understand the clinical implications of these preliminary results, for which the longitudinal design of ABCD will be crucial.

Goldblatt R, Holz N, Tate G, Sherman K, Ghebremicael S, Bhuyan SS, Al-Ajlouni Y, Santillanes S, Araya G, Abad S, Herting MM, Thapaliya B, Sapkota R, Xu J, Liu J; environMENTAL consortium; Schumann G, Calhoun VD. “Urban-Satellite” estimates in the ABCD Study: Linking Neuroimaging and Mental Health to Satellite Imagery Measurements of Macro Environmental Factors. medRxiv [Preprint]. 2023 Nov 7:2023.11.06.23298044. doi: 10.1101/2023.11.06.23298044. PMID: 37986844; PMCID: PMC10659457.

While numerous studies over the last decade have highlighted the important influence of environmental factors on mental health, globally applicable data on physical surroundings are still limited. Access to such data and the possibility to link them to epidemiological studies is critical to unlocking the relationship of environment, brain and behaviour and promoting positive future mental health outcomes. The Adolescent Brain Cognitive Development (ABCD) Study is the largest ongoing longitudinal and observational study exploring brain development and child health among children from 21 sites across the United States. Here we describe the linking of the ABCD study data with satellite-based “Urban-Satellite” (UrbanSat) variables consisting of 11 satellite-data derived environmental indicators associated with each subject’s residential address at their baseline visit, including land cover and land use, nighttime lights, and population characteristics. We present these UrbanSat variables and provide a review of the current literature that links environmental indicators with mental health, as well as key aspects that must be considered when using satellite data for mental health research. We also highlight and discuss significant links of the satellite data variables to the default mode network clustering coefficient and cognition. This comprehensive dataset provides the foundation for large-scale environmental epidemiology research.

Kiss O, Qu Z, Müller-Oehring EM, Baker FC, Mirzasoleiman B. Sleep, brain systems, and persistent stress in early adolescents during COVID-19: Insights from the ABCD study. J Affect Disord. 2023 Nov 7:S0165-0327(23)01355-1. doi: 10.1016/j.jad.2023.10.158. Epub ahead of print. PMID: 37944709.

Purpose: The first year of the COVID-19 pandemic constituted a major life stress event for many adolescents, associated with disrupted school, behaviors, social networks, and health concerns. However, pandemic-related stress was not equivalent for everyone and could have been influenced by pre-pandemic factors including brain structure and sleep, which both undergo substantial development during adolescence. Here, we analyzed clusters of perceived stress levels across the pandemic and determined developmentally relevant pre-pandemic risk factors in brain structure and sleep of persistently high stress during the first year of the COVID-19 pandemic.

Methods: We investigated longitudinal changes in perceived stress at six timepoints across the first year of the pandemic (May 2020-March 2021) in 5559 adolescents (50 % female; age range: 11-14 years) in the United States (U.S.) participating in the Adolescent Brain Cognitive Development (ABCD) study. In 3141 of these adolescents, we fitted machine learning models to identify the most important pre-pandemic predictors from structural MRI brain measures and self-reported sleep data that were associated with persistently high stress across the first year of the pandemic.

Results: Patterns of perceived stress levels varied across the pandemic, with 5 % reporting persistently high stress. Our classifiers accurately detected persistently high stress (AUC > 0.7). Pre-pandemic brain structure, specifically cortical volume in temporal regions, and cortical thickness in multiple parietal and occipital regions, predicted persistent stress. Pre-pandemic sleep difficulties and short sleep duration were also strong predictors of persistent stress, along with more advanced pubertal stage.

Conclusions: Adolescents showed variable stress responses during the first year of the COVID-19 pandemic, and some reported persistently high stress across the whole first year. Vulnerability to persistent stress was evident in several brain structural and self-reported sleep measures, collected before the pandemic, suggesting the relevance of other pre-existing individual factors beyond pandemic-related factors, for persistently high stress responses.

Kwon M, Kim H, Yang J, Lee Y, Hur JK, Lee TH, Bjork JM, Ahn WY. Caffeinated Soda Intake in Children Is Associated with Neurobehavioral Risk Factors for Substance Misuse. Subst Use Misuse. 2023 Nov 7:1-11. doi: 10.1080/10826084.2023.2259471. Epub ahead of print. PMID: 37936270.

Background and objectives: Use of psychotropic substances in childhood has been associated with both impulsivity and other manifestations of poor executive function as well as escalation over time to use of progressively stronger substances. However, how this relationship may start in earlier childhood has not been well explored. Here, we investigated the neurobehavioral correlates of daily caffeinated soda consumption in preadolescent children and examined whether caffeinated soda intake is associated with a higher risk of subsequent alcohol initiation.

Methods: Using Adolescent Brain Cognitive Development study data (N = 2,092), we first investigated cross-sectional relationships between frequent caffeinated soda intake and well-known risk factors of substance misuse: impaired working memory, high impulsivity, and aberrant reward processing. We then examined whether caffeinated soda intake at baseline predicts more alcohol sipping at 12 months follow-up using a machine learning algorithm.

Results: Daily consumption of caffeinated soda was cross-sectionally associated with neurobehavioral risk factors for substance misuse such as higher impulsivity scores and lower working memory performance. Furthermore, caffeinated soda intake predicted a 2.04 times greater likelihood of alcohol sipping after 12 months, even after controlling for rates of baseline alcohol sipping rates.

Conclusions: These findings suggest that previous linkages between caffeine and substance use in adolescence also extend to younger initiation, and may stem from core neurocognitive features thought conducive to substance initiation.

Fu, Z., Liu, J., Salman, M.S. et al. Functional connectivity uniqueness and variability? Linkages with cognitive and psychiatric problems in children. Nat. Mental Health (2023). https://doi.org/10.1038/s44220-023-00151-8

Brain functional connectivity (FC) derived from functional magnetic resonance imaging has been serving as a potential ‘fingerprint’ for adults. However, cross-scan variation of FC can be substantial and carries biological information, especially during childhood. Here we performed a large-scale cross-sectional analysis on cross-scan FC stability and its associations with a diverse range of health measures in children. Functional network connectivity (FNC) was extracted via a hybrid independent component analysis framework on 9,071 participants and compared across four scans. We found that FNC can identify a given child from a large group with high accuracy (maximum >94%) and replicated the results across multiple scans. We then performed a linear mixed-effects model to investigate how cross-scan FNC stability was predictive of children’s behaviour. Although we could not find strong relationships between FNC stability and children’s behaviour, we observed significant but small associations between them (maximum r = 0.1070), with higher stability correlated with better cognitive performance, longer sleep duration and less psychotic expression. Via a multivariate analysis method, we captured larger effects between FNC stability and children’s cognitive performance (maximum r = 0.2932), which further proved the relevance of FNC stability to neurocognitive development. Overall, our findings show that a child’s connectivity profile is not only intrinsic but also exhibits reliable variability across scans, regardless of brain growth and development. Cross-scan connectivity stability may serve as a valuable neuroimaging feature to draw inferences on early cognitive and psychiatric behaviours in children.

Dube SL, Johns MM, Robin L, Hoffman E, Potter AS. Comparison of Methods to Assess Adolescent Gender Identity in the ABCD Study. JAMA Pediatr. 2023 Nov 6. doi: 10.1001/jamapediatrics.2023.4678. Epub ahead of print. PMID: 37930714.

This cross-sectional study assesses the reliability and validity of methods used to capture gender identity in Adolescent Brain Cognitive Development (ABCD) Study participants.

Thapaliya B, Akbas E, Chen J, Sapkota R, Ray B, Suresh P, Calhoun V, Liu J. Brain Networks and Intelligence: A Graph Neural Network Based Approach to Resting State fMRI Data. ArXiv [Preprint]. 2023 Nov 6:arXiv:2311.03520v1. PMID: 37986729; PMCID: PMC10659448./

Resting-state functional magnetic resonance imaging (rsfMRI) is a powerful tool for investigating the relationship between brain function and cognitive processes as it allows for the functional organization of the brain to be captured without relying on a specific task or stimuli. In this paper, we present a novel modeling architecture called BrainRGIN for predicting intelligence (fluid, crystallized, and total intelligence) using graph neural networks on rsfMRI derived static functional network connectivity matrices. Extending from the existing graph convolution networks, our approach incorporates a clustering-based embedding and graph isomorphism network in the graph convolutional layer to reflect the nature of the brain sub-network organization and efficient network expression, in combination with TopK pooling and attention-based readout functions. We evaluated our proposed architecture on a large dataset, specifically the Adolescent Brain Cognitive Development Dataset, and demonstrated its effectiveness in predicting individual differences in intelligence. Our model achieved lower mean squared errors and higher correlation scores than existing relevant graph architectures and other traditional machine learning models for all of the intelligence prediction tasks. The middle frontal gyrus exhibited a significant contribution to both fluid and crystallized intelligence, suggesting their pivotal role in these cognitive processes. Total composite scores identified a diverse set of brain regions to be relevant which underscores the complex nature of total intelligence.

Langensee L, Spotorno N, Mårtensson J. Beyond the language network: Associations between reading, receptive vocabulary, and grey matter volume in 10-year-olds. Neuropsychologia. 2023 Nov 6:108719. doi: 10.1016/j.neuropsychologia.2023.108719. Epub ahead of print. PMID: 37939873.

Most research on the neurostructural basis of language abilities in children stems from small samples and surface-based measures. To complement and expand the existent knowledge, we investigated associations between grey matter volume and language performance in a large sample of 9-to-11-year-old children, using data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 1865) and an alternative measure of grey matter morphology. We estimated whole-brain grey matter volume for one half of the sample (N = 939) and tested for correlations with scores on a picture vocabulary and a letter and word reading test, with and without factoring in general intelligence and total grey matter volume as additional covariates. The initial analyses yielded correlations between grey matter in the right occipital fusiform gyrus, the right lingual gyrus, and the cerebellum for both vocabulary and reading. Employing the significant clusters from the first analyses as regions of interest in the second half of the cohort (N = 926) in correlational and multiple regression analyses suggests the cluster in the right occipital fusiform and lingual gyri to be most robust. Overall, the amount of variance explained by grey matter volume is limited and factoring in additional covariates paints an inconsistent picture. The present findings reinforce existent doubt with respect to explaining individual differences in reading and vocabulary performance based on unique contributions of macrostructural brain features.

Martino RM, Weissman DG, McLaughlin KA, Hatzenbuehler ML. Associations Between Structural Stigma and Psychopathology Among Early Adolescents. J Clin Child Adolesc Psychol. 2023 Nov 2:1-11. doi: 10.1080/15374416.2023.2272936. Epub ahead of print. PMID: 37916808.

Objective: Ample evidence demonstrates that structural stigma – defined as societal-level conditions, cultural norms, and institutional policies and practices that constrain opportunities, resources, and well-being of stigmatized populations – is associated with psychopathology in adults from marginalized groups. Yet there is limited research on whether structural stigma is similarly associated with internalizing and externalizing symptoms among youth.

Method: Structural stigma related to sex, sexual orientation, race, and Latinx ethnicity was measured using indicators of state-level policy and aggregated attitudes. Using data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 10,414; M age = 12 years, SD = 0.66; 48% female, 6.8% lesbian, gay, and bisexual (LGB), 13.4% Black, 20% Latinx), we examined associations of structural stigma with internalizing and externalizing symptoms among female, LGB, Black, and Latinx youth.

Results: LGB youth living in higher (vs. lower) structural stigma states had elevated levels of internalizing and externalizing symptoms. In lower structural stigma states, there were no differences in externalizing symptoms between LGB and heterosexual youth. Similarly, Latinx youth and females living in higher (vs. lower) structural stigma states had elevated levels of externalizing symptoms. In lower structural stigma states, there were no differences in externalizing symptoms between Latinx youth and non-Latinx White youth. Structural stigma related to race was unrelated to internalizing or externalizing symptoms for Black youth.

Conclusions: This study provides novel evidence that macro-level social environments, in the form of structural stigma, contribute to adverse mental health outcomes for marginalized youth and partly explain disparities in externalizing symptoms.

Mummaneni A, Kardan O, Stier AJ, Chamberlain TA, Chao AF, Berman MG, Rosenberg MD. Functional brain connectivity predicts sleep duration in youth and adults. Hum Brain Mapp. 2023 Nov 2. doi: 10.1002/hbm.26488. Epub ahead of print. PMID: 37916784.

Sleep is critical to a variety of cognitive functions and insufficient sleep can have negative consequences for mood and behavior across the lifespan. An important open question is how sleep duration is related to functional brain organization which may in turn impact cognition. To characterize the functional brain networks related to sleep across youth and young adulthood, we analyzed data from the publicly available Human Connectome Project (HCP) dataset, which includes n-back task-based and resting-state fMRI data from adults aged 22-35 years (task n = 896; rest n = 898). We applied connectome-based predictive modeling (CPM) to predict participants’ mean sleep duration from their functional connectivity patterns. Models trained and tested using 10-fold cross-validation predicted self-reported average sleep duration for the past month from n-back task and resting-state connectivity patterns. We replicated this finding in data from the 2-year follow-up study session of the Adolescent Brain Cognitive Development (ABCD) Study, which also includes n-back task and resting-state fMRI for adolescents aged 11-12 years (task n = 786; rest n = 1274) as well as Fitbit data reflecting average sleep duration per night over an average duration of 23.97 days. CPMs trained and tested with 10-fold cross-validation again predicted sleep duration from n-back task and resting-state functional connectivity patterns. Furthermore, demonstrating that predictive models are robust across independent datasets, CPMs trained on rest data from the HCP sample successfully generalized to predict sleep duration in the ABCD Study sample and vice versa. Thus, common resting-state functional brain connectivity patterns reflect sleep duration in youth and young adults.

Burke TA, Bettis AH, Walsh RFL, Levin RY, Lawrence HR, Sheehan AE, Turnamian MR, Liu RT. Nonsuicidal Self-Injury in Preadolescents. Pediatrics. 2023 Nov 2:e2023063918. doi: 10.1542/peds.2023-063918. Epub ahead of print. PMID: 37916265.

Objectives: There is a dearth of literature on the prevalence and predictors of nonsuicidal self-injury (NSSI) history and onset among preadolescent youth. This gap in the literature is significant given evidence suggesting that NSSI is a robust predictor of negative mental health outcomes, and that early onset NSSI may be associated with a more severe course of self-injurious thoughts and behaviors. This study aimed to evaluate sociodemographic characteristics, psychiatric disorders, and suicidal ideation (SI) in relation to NSSI onset and history in preadolescents.

Methods: Data were drawn from the Adolescent Brain and Cognitive Development (ABCD) study, which recruited a diverse sample of 11 875 youth aged 9 to 10 years. The primary outcome measures were lifetime history and recent onset of NSSI. Measures included sociodemographics and the K-SADS diagnostic interview assessing psychopathology and SI.

Results: Female sex and identifying as Black were associated with lower odds of lifetime NSSI. Identifying as a sexual minority, having unmarried parents, and a low family income were associated with higher odds of lifetime NSSI. Although depression was most predictive of NSSI history and onset, a range of internalizing and externalizing disorders, greater comorbidity, and SI also were predictive.

Conclusions: Given that NSSI was associated with a range of mental health disorders and comorbidity, it may be best conceptualized as a transdiagnostic phenomenon. Findings highlight key sociodemographic and diagnostic factors that may help to direct screening efforts in preadolescents, particularly sexual minority status and depression.

Zhang Y, Choi KW, Delaney SW, Ge T, Pingault JB, Tiemeier H. Shared Genetic Risk in the Association of Screen Time With Psychiatric Problems in Children. JAMA Netw Open. 2023 Nov 1;6(11):e2341502. doi: 10.1001/jamanetworkopen.2023.41502. PMID: 37930702.

Importance: Children’s exposure to screen time has been associated with poor mental health outcomes, yet the role of genetic factors remains largely unknown.

Objective: To assess the extent of genetic confounding in the associations between screen time and attention problems or internalizing problems in preadolescent children.

Design, setting, and participants: This cohort study analyzed data obtained between 2016 and 2019 from the Adolescent Brain Cognitive Development Study at 21 sites in the US. The sample included children aged 9 to 11 years of genetically assigned European ancestry with self-reported screen time. Data were analyzed between November 2021 and September 2023.

Exposure: Child-reported daily screen time (in hours) was ascertained from questionnaires completed by the children at baseline.

Main outcomes and measures: Child psychiatric problems, specifically attention and internalizing problems, were measured with the parent-completed Achenbach Child Behavior Checklist at the 1-year follow-up. Genetic sensitivity analyses model (Gsens) was used, which incorporated polygenic risk scores (PRSs) of both exposure and outcomes as well as either single-nucleotide variant (SNV; formerly single-nucleotide polymorphism)-based heritability or twin-based heritability to estimate genetic confounding.

Results: The 4262 children in the sample included 2269 males (53.2%) with a mean (SD) age of 9.9 (0.6) years. Child screen time was associated with attention problems (β = 0.10 SD; 95% CI, 0.07-0.13 SD) and internalizing problems (β = 0.03 SD; 95% CI, 0.003-0.06 SD). The television time PRS was associated with child screen time (β = 0.18 SD; 95% CI, 0.14-0.23 SD), the attention-deficit/hyperactivity disorder PRS was associated with attention problems (β = 0.13 SD; 95% CI, 0.10-0.16 SD), and the depression PRS was associated with internalizing problems (β = 0.10 SD; 95% CI, 0.07-0.13 SD). These PRSs were associated with cross-traits, suggesting genetic confounding. Estimates using PRSs and SNV-based heritability showed that genetic confounding accounted for most of the association between child screen time and attention problems and for 42.7% of the association between child screen time and internalizing problems. When PRSs and twin-based heritability estimates were used, genetic confounding fully explained both associations.

Conclusions and relevance: Results of this study suggest that genetic confounding may explain a substantial part of the associations between child screen time and psychiatric problems. Genetic confounding should be considered in sociobehavioral studies of modifiable factors for youth mental health.

Karcher NR, Modi H, Kochunov P, Gao S, Barch DM. Regional Vulnerability Indices in Youth With Persistent and Distressing Psychoticlike Experiences. JAMA Netw Open. 2023 Nov 1;6(11):e2343081. doi: 10.1001/jamanetworkopen.2023.43081. PMID: 37955897.

Importance: Distressing and persistent psychoticlike experiences (PLEs) in youth are associated with greater odds of developing psychiatric conditions in adulthood. Despite this risk, it is unclear whether early PLEs show similar brain patterns compared with adults with psychiatric and neurologic conditions.

Objective: To examine the degree to which persistent and distressing PLEs exhibit neural metrics that show similarity to adults with chronic psychiatric and neurologic conditions.

Design, setting, and participants: This cohort study used Adolescent Brain Cognitive Development (ABCD) Study examining the persistence and distress associated with PLEs across the first 3 waves of data with baseline structural magnetic resonance imaging data. Analyzed data were collected between September 1, 2016, and September 27, 2021. Children were recruited from 21 research sites across the US.

Exposures: Psychoticlike experiences were assessed using the Prodromal Questionnaire-Brief Child Version, and participants were categorized into groups based on the persistence and distress associated with PLEs.

Main outcomes and measures: Cortical and subcortical regional vulnerability indices (RVIs) were created by quantifying the similarity of participants’ baseline neuroimaging measures to the expected patterns found in adult neuropsychiatric samples. The PLE groups were compared on the following RVI cortical and subcortical metrics: schizophrenia spectrum disorders, bipolar disorder, major depressive disorder, Parkinson disease, Alzheimer disease, and metabolic diseases.

Results: Analyses examined PLE groups created from 8242 children in the ABCD sample (52.5% male; mean [SD] age, 9.93 [0.63] years; and 56.3% White), including persistent distressing PLEs (n = 329), transient distressing PLEs (n = 396), persistent nondistressing PLEs (n = 234), transient nondistressing PLEs (n = 390), and low distressing PLEs (n = 6893) groups. Participants with persistent or transient distressing PLEs broadly showed increased subcortical RVI scores across most RVI metrics, with persistent distressing PLEs additionally showing increased scores for cortical RVI metrics. The greatest effect sizes were found for persistent distressing PLEs with cortical RVI-schizophrenia spectrum disorders (β estimate, 1.055; 95% CI, 0.326-1.786) and RVI-Alzheimer disease (β estimate, 2.473; 95% CI, 0.930-4.018).

Conclusions and relevance: In this cohort study of ABCD participants, the findings suggest that especially the persistent distressing PLEs in children were associated with neural metrics resembling those observed in adults with severe psychiatric and neurologic conditions. These findings support the potential use of brain-based risk scores for early identification and precision medicine approaches in the assessment of PLEs.

Gorelik AJ, Paul SE, Miller AP, Baranger DAA, Lin S, Zhang W, Elsayed NM, Modi H, Addala P, Bijsterbosch J, Barch DM, Karcher NR, Hatoum AS, Agrawal A, Bogdan R, Johnson EC. Associations Between Polygenic Scores for Cognitive and Non-cognitive Factors of Educational Attainment and Measures of Behavior, Psychopathology, and Neuroimaging in the Adolescent Brain Cognitive Development Study. medRxiv [Preprint]. 2023 Oct 28:2023.10.27.23297675. doi: 10.1101/2023.10.27.23297675. PMID: 37961716; PMCID: PMC10635216.

Background: Both cognitive and non-cognitive (e.g., traits like curiosity) factors are critical for social and emotional functioning and independently predict educational attainment. These factors are heritable and genetically correlated with a range of health-relevant traits and behaviors in adulthood (e.g., risk-taking, psychopathology). However, whether these associations are present during adolescence, and to what extent these relationships diverge, could have implications for adolescent health and well-being.

Methods: Using data from 5,517 youth of European ancestry from the ongoing Adolescent Brain Cognitive Development SM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and outcomes related to cognition, socioeconomic status, risk tolerance and decision-making, substance initiation, psychopathology, and brain structure.

Results: Cognitive and non-cognitive PGSs were both positively associated with cognitive performance and family income, and negatively associated with ADHD and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk-taking, delayed discounting, and anorexia, as well as lower likelihood of nicotine initiation. The cognitive PGS was further associated with cognition scores and anorexia in within-sibling analyses, suggesting these results do not solely reflect the effects of assortative mating or passive gene-environment correlations. The cognitive PGS showed significantly stronger associations with cortical volumes than the non-cognitive PGS and was associated with right hemisphere caudal anterior cingulate and pars-orbitalis in within-sibling analyses, while the non-cognitive PGS showed stronger associations with white matter fractional anisotropy and a significant within-sibling association for right superior corticostriate-frontal cortex.

Conclusions: Our findings suggest that PGSs for cognitive and non-cognitive factors show similar associations with cognition and socioeconomic status as well as other psychosocial outcomes, but distinct associations with regional neural phenotypes in this adolescent sample.

Hoffman KW, Tran KT, Moore TM, Gataviņš MM, Visoki E, DiDomenico GE, Schultz LM, Almasy L, Hayes MR, Daskalakis NP, Barzilay R. Allostatic load in early adolescence: gene / environment contributions and relevance for mental health. medRxiv [Preprint]. 2023 Oct 28:2023.10.27.23297674. doi: 10.1101/2023.10.27.23297674. PMID: 37961462; PMCID: PMC10635214.

Background: Allostatic load is the cumulative “wear and tear” on the body due to chronic adversity. We aimed to test poly-environmental (exposomic) and polygenic contributions to allostatic load and their combined contribution to early adolescent mental health.

Methods: We analyzed data on N = 5,035 diverse youth (mean age 12) from the Adolescent Brain Cognitive Development Study (ABCD). Using dimensionality reduction method, we calculated and overall allostatic load score (AL) using body mass index [BMI], waist circumference, blood pressure, blood glycemia, blood cholesterol, and salivary DHEA. Childhood exposomic risk was quantified using multi-level environmental exposures before age 11. Genetic risk was quantified using polygenic risk scores (PRS) for metabolic system susceptibility (type 2 diabetes [T2D]) and stress-related psychiatric disease (major depressive disorder [MDD]). We used linear mixed effects models to test main, additive, and interactive effects of exposomic and polygenic risk (independent variables) on AL (dependent variable). Mediation models tested the mediating role of AL on the pathway from exposomic and polygenic risk to youth mental health. Models adjusted for demographics and genetic principal components.

Results: We observed disparities in AL with non-Hispanic White youth having significantly lower AL compared to Hispanic and Non-Hispanic Black youth. In the diverse sample, childhood exposomic burden was associated with AL in adolescence (beta=0.25, 95%CI 0.22-0.29, P<.001). In European ancestry participants ( n =2,928), polygenic risk of both T2D and depression was associated with AL (T2D-PRS beta=0.11, 95%CI 0.07-0.14, P<.001; MDD-PRS beta=0.05, 95%CI 0.02-0.09, P=.003). Both polygenic scores showed significant interaction with exposomic risk such that, with greater polygenic risk, the association between exposome and AL was stronger. AL partly mediated the pathway to youth mental health from exposomic risk and from MDD-PRS, and fully mediated the pathway from T2D-PRS.

Conclusions: AL can be quantified in youth using anthropometric and biological measures and is mapped to exposomic and polygenic risk. Main and interactive environmental and genetic effects support a diathesis-stress model. Findings suggest that both environmental and genetic risk be considered when modeling stress-related health conditions.

Thomas SA, Ryan SK, Gilman J. Resting state network connectivity is associated with cognitive flexibility performance in youth in the adolescent brain cognitive development study. Neuropsychologia. 2023 Oct 26:108708. doi: 10.1016/j.neuropsychologia.2023.108708. Epub ahead of print. PMID: 37898357.

Cognitive flexibility is an executive functioning skill that develops in childhood, and when impaired, has transdiagnostic implications for psychiatric disorders. To identify how intrinsic neural architecture at rest is linked to cognitive flexibility performance, we used the data-driven method of Independent Components Analysis (ICA) to investigate resting state networks (RSNs) and their whole-brain connectivity associated with levels of cognitive flexibility performance in children. We hypothesized differences by cognitive flexibility performance in RSN connectivity strength in cortico-striatal circuitry, which would manifest via the executive control network, right and left frontoparietal networks (FPN), salience network, default mode network (DMN), and basal ganglia network. We selected participants from the Adolescent Brain Cognitive Development (ABCD) Study who scored at the 25th, (“CF-Low”), 50th (“CF-Average”), or 75th percentiles (“CF-High”) on a cognitive flexibility task, were early to middle puberty, and did not exhibit significant psychopathology (n = 967, 47.9% female; ages 9-10). We conducted whole-brain ICA, identifying 14 well-characterized RSNs. Groups differed in connectivity strength in the right FPN, anterior DMN, and posterior DMN. Planned comparisons indicated CF-High had stronger connectivity between right FPN and supplementary motor/anterior cingulate than CF-Low. CF-High had more anti-correlated connectivity between anterior DMN and precuneus than CF-Average. CF-Low had stronger connectivity between posterior DMN and supplementary motor/anterior cingulate than CF-Average. Post-hoc correlations with reaction time by trial type demonstrated significant associations with connectivity. In sum, our results suggest childhood cognitive flexibility performance is associated with DMN and FPN connectivity strength at rest, and that there may be optimal levels of connectivity associated with task performance that vary by network.

Al-Shoaibi AAA, Iyra P, Raney JH, Ganson KT, Dooley EE, Testa A, Jackson DB, Gabriel KP, Baker FC, Nagata JM. Associations between adverse childhood experiences and early adolescent physical activity in the United States. Acad Pediatr. 2023 Oct 26:S1876-2859(23)00395-9. doi: 10.1016/j.acap.2023.10.004. Epub ahead of print. PMID: 37898383.

Objective: To determine the associations between the number of adverse childhood experiences (ACEs) and objectively-measured physical activity (PA) in a population-based, demographically diverse cohort of 9-14-year-olds and to determine which subtypes of ACEs were associated with physical activity levels.

Methods: We analyzed data (n=7,046) from the Adolescent Brain Cognitive Development (ABCD) Study 4.0 release at baseline and year 2 follow-up. ACE (cumulative score and subtypes) and physical activity (average Fitbit daily steps assessed at Year 2) were analyzed using linear regression analyses. Covariates included race/ethnicity, sex, household income, parent education, body mass index, study site, twins/siblings, and data collection period.

Results: Adjusted models suggest an inverse association between number of ACEs and Fitbit daily steps, with ≥4 (compared to 0) ACEs associated with 526 fewer daily steps (95% CI -882.7, -222.6). Of the ACEs subtypes, emotional abuse (B= -716.8, 95% CI -1408.3, -25.3), physical neglect (B= -373.6, 95% CI -690.4, -56.7), household mental illness (B= -287.7, 95% CI -454.6, -120.7), and household divorce or separation (B= -24.1, 95% CI –482.1, -8.22) were inversely and statistically significant associated with Fitbit daily steps after adjusting for confounders.

Conclusions: Our results suggest that there is an inverse, dose-dependent relationship between cumulative number of ACEs and physical activity as measured by daily steps. This work highlights the importance of screening for ACEs among young people at an early age to help identify those who could benefit from interventions or community programs that support increased physical activity.

de Lacy N, Ramshaw MJ. Predicting new onset thought disorder in early adolescence with optimized deep learning implicates environmental-putamen interactions. medRxiv [Preprint]. 2023 Oct 24:2023.10.23.23297438. doi: 10.1101/2023.10.23.23297438. PMID: 37961085; PMCID: PMC10635181.

Background: Thought disorder (TD) is a sensitive and specific marker of risk for schizophrenia onset. Specifying factors that predict TD onset in adolescence is important to early identification of youth at risk. However, there is a paucity of studies prospectively predicting TD onset in unstratified youth populations.

Study design: We used deep learning optimized with artificial intelligence (AI) to analyze 5,777 multimodal features obtained at 9-10 years from youth and their parents in the ABCD study, including 5,014 neural metrics, to prospectively predict new onset TD cases at 11-12 years. The design was replicated for all prevailing TD cases at 11-12 years.

Study results: Optimizing performance with AI, we were able to achieve 92% accuracy and F1 and 0.96 AUROC in prospectively predicting the onset of TD in early adolescence. Structural differences in the left putamen, sleep disturbances and the level of parental externalizing behaviors were specific predictors of new onset TD at 11-12 yrs, interacting with low youth prosociality, the total parental behavioral problems and parent-child conflict and whether the youth had already come to clinical attention. More important predictors showed greater inter-individual variability.

Conclusions: This study provides robust person-level, multivariable signatures of early adolescent TD which suggest that structural differences in the left putamen in late childhood are a candidate biomarker that interacts with psychosocial stressors to increase risk for TD onset. Our work also suggests that interventions to promote improved sleep and lessen parent-child psychosocial stressors are worthy of further exploration to modulate risk for TD onset.

Taylor JJ, Palm ST, Cohen AL, Croarkin PE, Drew W, Fox MD, Siddiqi S. Brain Circuits Involved in Transcranial Magnetic Stimulation Response in Adults Are Connected to a Similar Prefrontal Target in Children. Biol Psychiatry. 2023 Oct 24:S0006-3223(23)01531-7. doi: 10.1016/j.biopsych.2023.08.019. Epub ahead of print. PMID: 37877924.

Gebru NM, Goncalves PD, Cruz RA, Thompson WK, Allegair N, Potter A, Garavan H, Dumas J, Leeman RF, Johnson M. Effects of parental mental health and family environment on impulsivity in preadolescents: a longitudinal ABCD study®. Front Behav Neurosci. 2023 Oct 24;17:1213894. doi: 10.3389/fnbeh.2023.1213894. PMID: 37942273; PMCID: PMC10628051.

Introduction: Impulsivity is a known risk factor for the development of substance use disorders and other psychiatric conditions that is influenced by both genetics and environment. Although research has linked parental mental health to children’s impulsivity, potential mediators of this relationship remain understudied. The current investigation leverages the large national Adolescent Brain Cognitive Development (ABCD) Study to assess the mediating role of family conflict – an important social context for youth development – in the relationship between parental mental health and youth impulsivity.

Methods: Data were from the first three annual waves of the ABCD study (Baseline N = 11,876 children, Mage = 9.9 years; 48% female; 52% White). Parental mental health conditions were self-reported internalizing, externalizing, and total problems. Youth completed the family conflict scale, and Urgency, Planning (lack of), Perseverance (lack of), Sensation Seeking, and Positive Urgency (UPPS-P) scale to measure impulsivity. To determine if within-family change in conflict from baseline to year 1 explained changes in the strength of relations between baseline parental mental health and year 2 youth impulsivity, longitudinal causal mediation analyses were conducted, controlling for demographic factors (i.e., age, sex, race, household income, parental education, marital status), as well as baseline levels of family conflict and outcomes. Separate mediation models were run for each mental health condition and each UPPS-P subscale.

Results: Above and beyond bivariate relations, longitudinal mediation models, which included covariates, showed family conflict significantly (ps < 0.001) mediated relations between all three parental mental health conditions and all but one (i.e., sensation seeking) UPPS-P subscales. The proportion mediated through family conflict for internalizing problems and total problems on facets of impulsivity (except sensation seeking) ranged from 9% (for lack of perseverance) to 17% (for lack of planning). Proportion mediated via family conflict for externalizing problems on youth’s impulsivity (except sensation seeking) was slightly higher, ranging between 13% (lack of perseverance) to 21% (lack of planning).

Discussion: Family conflict may be an important intergenerational factor linking parental mental health and youth’s impulsivity. Addressing parental mental health and family conflict may help curb increased impulsivity in youth, and in turn reduce adolescent substance use disorders.

Kraft D, Alnæs D, Kaufmann T. Domain adapted brain network fusion captures variance related to pubertal brain development and mental health. Nat Commun. 2023 Oct 23;14(1):6698. doi: 10.1038/s41467-023-41839-w. PMID: 37872174.

Puberty demarks a period of profound brain dynamics that orchestrates changes to a multitude of neuroimaging-derived phenotypes. This complexity poses a dimensionality problem when attempting to chart an individual’s brain development over time. Here, we illustrate that shifts in subject similarity of brain imaging data relate to pubertal maturation in the longitudinal ABCD study. Given that puberty depicts a critical window for emerging mental health issues, we additionally show that our model is capable of capturing variance in the adolescent brain related to psychopathology in a population-based and a clinical cohort. These results suggest that low-dimensional reference spaces based on subject similarities render useful to chart variance in brain development in youths.

Kant T, Koyama E, Zai CC, Sanches M, Beitchman JH, Kennedy JL. COMT Val/Met, stressful life events and externalizing behaviors in youth: A longitudinal study from the ABCD sample. Heliyon. 2023 Oct 21;9(11):e21126. doi: 10.1016/j.heliyon.2023.e21126. PMID: 38027832; PMCID: PMC10665666.

Early adolescence is a crucial time for understanding and detecting the risk factors that may influence youth externalizing/disruptive behaviors and disorders. Previous literature reported evidence that risk factors for disruptive behaviors include catechol-O-methyltransferase (COMT) Val158Met (rs4680) polymorphism and environmental influences. An unanswered question is whether there is a change in these risk factors over stages of youth development. This longitudinal study examines the interaction effect of Val158Met and stressful life events (SLE) on youth externalizing behaviors from ages 9-11. Participants were 2363 children of European ancestry recruited as part of the Adolescent Brain Cognitive Development study. Repeated measures linear mixed models were used to examine the effect of the interaction between Val158Met and SLE (G × E) on disruptive behaviors over development. Externalizing behaviors were analyzed at both baseline and two-year follow-up. Both Val158Met genotype and SLE scores demonstrated significant main effects on disruptive behaviors in youth, and those effects were consistent at both time points. G × E was not associated with externalizing behaviors. Youth who carried the Val allele and/or were exposed to higher SLE consistently had increased externalizing behavior scores. To our knowledge, this is the first study to longitudinally examine the interaction effects of Val158Met and SLE on externalizing behaviors in youth. The results highlight the importance of understanding the genetic and environmental factors underlying externalizing behaviors for better detection of at-risk youth, helping further with early prevention efforts. The findings propose that COMT Val158Met genotype may act as a biomarker for development of novel treatment strategies for disruptive behaviors.

Campbell CE, Cotter DL, Bottenhorn KL, et al. (In Press, 2023). Air pollution and age-dependent changes in emotional behavior across early adolescence in the U.S. Environmental Research. Available online 21 October 2023, 117390. https://doi.org/10.1016/j.envres.2023.117390

Recent studies have linked air pollution to increased risk for behavioral problems during development, albeit with inconsistent findings. Additional longitudinal studies are needed that consider how emotional behaviors may be affected when exposure coincides with the transition to adolescence – a vulnerable time for developing mental health difficulties. This study investigates if annual average PM2.5 and NO2 exposure at ages 9–10 years moderates age-related changes in internalizing and externalizing behaviors over a 2-year follow-up period in a large, nationwide U.S. sample of participants from the Adolescent Brain Cognitive Development (ABCD) Study®. Air pollution exposure was estimated based on the residential address of each participant using an ensemble-based modeling approach. Caregivers answered questions from the Child Behavior Checklist (CBCL) at the baseline, 1-year follow-up, and 2-year follow-up visits, for a total of 3 waves of data; from the CBCL we obtained scores on internalizing and externalizing problems plus 5 syndrome scales (anxious/depressed, withdrawn/depressed, rule-breaking behavior, aggressive behavior, and attention problems). Zero-inflated negative binomial models were used to examine both the main effect of age as well as the interaction of age with each pollutant on behavior while adjusting for various socioeconomic and demographic characteristics. Against our hypothesis, there was no evidence that greater air pollution exposure was related to more behavioral problems with age over time.

Misztal MC, Tio ES, Mohan A, Felsky D. Interactions between genetic risk for 21 neurodevelopmental and psychiatric disorders and sport activity on youth mental health. Psychiatry Res. 2023 Oct 20;330:115550. doi: 10.1016/j.psychres.2023.115550. Epub ahead of print. PMID: 37973444.

Childhood is a sensitive period where behavioral disturbances, determined by genetics and environmental factors including sport activity, may emerge and impact risk of mental illness in adulthood. We aimed to determine if participation in sports can mitigate genetic risk for neurodevelopmental and psychiatric disorders in youth. We analyzed 4975 unrelated European youth (ages 9-10) from the Adolescent Brain Cognitive Development Study. Our outcomes were eight Child Behavior Checklist (CBCL) scores, measured annually. Polygenic risk scores (PRSs) were calculated for 21 disorders, and sport frequency and type were summarized. PRSs and sport variables were tested for main effects and interactions against CBCL outcomes using linear models. Cross-sectionally, PRSs for attention-deficit/hyperactivity disorder and major depressive disorder were associated with increases in multiple CBCL outcomes. Participation in non-contact or team sports, as well as more frequent sport participation reduced all cross-sectional CBCL outcomes, whereas involvement in contact sports increased attention problems and rule-breaking behavior. Interactions revealed that more frequent exercise was significantly associated with less rule breaking behavior in individuals with high genetic risk for obsessive compulsive disorder. Associations with longitudinal CBCL outcomes demonstrated weaker effects. We highlight the importance of genetic context when considering sports as an intervention for early life behavioural problems.

Miller J, Mills KL, Vuorre M, Orben A, Przybylski AK. Impact of digital screen media activity on functional brain organization in late childhood: Evidence from the ABCD study. Cortex. 2023 Oct 19;169:290-308. doi: 10.1016/j.cortex.2023.09.009. Epub ahead of print. PMID: 37976871.

The idea that the increased ubiquity of digital devices negatively impacts neurodevelopment is as compelling as it is disturbing. This study investigated this concern by systematically evaluating how different profiles of screen-based engagement related to functional brain organization in late childhood. We studied participants from a large and representative sample of young people participating in the first two years of the ABCD study (ages 9-12 years) to investigate the relations between self-reported use of various digital screen media activity (SMA) and functional brain organization. A series of generalized additive mixed models evaluated how these relationships related to functional outcomes associated with health and cognition. Of principal interest were two hypotheses: First, that functional brain organization (assessed through resting state functional connectivity MRI; rs-fcMRI) is related to digital screen engagement; and second, that children with higher rates of engagement will have functional brain organization profiles related to maladaptive functioning. Results did not support either of these predictions for SMA. Further, exploratory analyses predicting how screen media activity impacted neural trajectories showed no significant impact of SMA on neural maturation over a two-year period.

Harris JC, Liuzzi MT, Malames BA, Larson CL, Lisdahl KM. Differences in parent and youth perceived neighborhood threat on nucleus accumbens-frontoparietal network resting state connectivity and alcohol sipping in children enrolled in the ABCD study. Front Psychiatry. 2023 Oct 18;14:1237163. doi: 10.3389/fpsyt.2023.1237163. PMID: 37928910; PMCID: PMC10622767.

Purpose: Evidence has shown neighborhood threat (NT) as a social driver of emotional and brain development. Few studies have examined the relationship between NT and neural function. Altered functional connectivity in the nucleus accumbens (NAcc) with the frontoparietal network (FPN) has been implicated in the development of substance use, however, little is known about perceived NT-related brain function or downstream alcohol sipping during early adolescence. This study examined the longitudinal relationship between youth and combined youth/parent perceived NT, resting state functional connectivity (RSFC) of the NAcc-FPN, and alcohol sipping behavior during late childhood and preadolescence.

Methods: This study used data (N = 7,744) from baseline to 2-year follow-up (FU) of the Adolescent Brain Cognitive Development Study (ABCD; Release 4.0). Relationships between youth and combined youth/parent perceive NT, alcohol sipping (baseline to two-year FU), and NAcc-FPN (left/right) connectivity, adjusting for demographics, family/peer history of alcohol use, parental monitoring and warmth, externalizing symptoms, and site, were examined in a mediation model via PROCESS in R.

Results: Greater youth-reported NT at baseline was significantly associated with lower RSFC between the right (but not left) NAcc-FPN holding covariates constant (R2 = 0.01, B = -0.0019 (unstandardized), F (12, 7,731) = 8.649, p = 0.0087) and increased odds of alcohol sipping at baseline up to the two-year FU (direct effect = 0.0731, 95% CI = 0.0196, 0.1267). RSFC between the right NAcc-FPN did not significantly predict alcohol sipping at the two-year FU (b = -0.0213, SE = 0.42349, p = 0.9599; 95% CI = -0.8086, 0.8512). No significant relationships were observed for combined youth/parent report predicting alcohol sipping or NAcc-FPN connectivity.

Conclusion: Findings suggest notable reporting differences in NT. Combined youth/parent report did not reveal significant findings; youth perceived NT was related to increased likelihood of alcohol sipping and lower neural connectivity between the right NAcc-FPN during late childhood and early adolescence. NT context – and source of reporting – may be crucial in examining links with downstream neuronal function and health behaviors. Future research should investigate reward processing and threat as the cohort ages into later adolescence.
37928910

Zink J, O’Connor SG, Blachman-Demner DR, Wolff-Hughes DL, Berrigan D. Examining the Bidirectional Associations Between Sleep Duration, Screen Time, and Internalizing Symptoms in the ABCD Study. J Adolesc Health. 2023 Oct 17:S1054-139X(23)00484-6. doi: 10.1016/j.jadohealth.2023.09.001. Epub ahead of print. PMID: 37855753.

Purpose: The likelihood of meeting sleep duration and screen time guidelines decreases as children develop toward adolescence. Simultaneously, the prevalence of internalizing symptoms increases. The purpose of this paper was to examine the bidirectional associations between sleep duration and screen time with internalizing symptoms in a one-year longitudinal study starting in late childhood.

Methods: Participants were 10,828 youth (47.8% female) enrolled in the Adolescent Brain Cognitive Development Study. At baseline (mean age 9.9 years) and one-year follow-up (mean age 10.9 years), youth self-reported screen time for weekdays and weekend days. Responses were separately dichotomized as >2 versus ≤2 hours/day (meeting behavioral guidelines). Caregiver-reported youth sleep duration was dichotomized as <9 versus 9-11 hours/night (meeting behavioral guidelines). Caregivers reported internalizing symptoms via the child behavior checklist. The withdrawn/depressed, anxious/depressed, and somatic symptom child behavior checklist subscale t-scores were separately dichotomized as ≥65 (borderline clinical levels of symptoms and above) versus <65. Analyses were gender-stratified.

Results: In females, longer baseline sleep duration was protective against withdrawn/depressed symptoms (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.4-0.8) and somatic complaints (OR 0.8, 95% CI 0.6-0.97) one year later. In females, greater baseline weekend screen time was associated with increased risk of withdrawn/depressed symptoms (OR 1.6, 95% CI 1.1-2.2) one year later. No other significant associations were observed.

Discussion: Longitudinal associations between sleep duration, weekend screen time, and internalizing symptoms were unidirectional (behavior preceding internalizing symptoms), among females only, and specific to withdrawn/depressed and somatic symptoms. These prospective study findings warrant attention and inform future research in this cohort.

Xiao Y, Mann JJ, Chow JC, Brown TT, Snowden LR, Yip PS, Tsai AC, Hou Y, Pathak J, Wang F, Su C. Patterns of Social Determinants of Health and Child Mental Health, Cognition, and Physical Health. JAMA Pediatr. 2023 Oct 16. doi: 10.1001/jamapediatrics.2023.4218. Epub ahead of print. PMID: 37843837.

Importance: Social determinants of health (SDOH) influence child health. However, most previous studies have used individual, small-set, or cherry-picked SDOH variables without examining unbiased computed SDOH patterns from high-dimensional SDOH factors to investigate associations with child mental health, cognition, and physical health.

Objective: To identify SDOH patterns and estimate their associations with children’s mental, cognitive, and physical developmental outcomes.

Design, setting, and participants: This population-based cohort study included children aged 9 to 10 years at baseline and their caregivers enrolled in the Adolescent Brain Cognitive Development (ABCD) Study between 2016 and 2021. The ABCD Study includes 21 sites across 17 states.

Exposures: Eighty-four neighborhood-level, geocoded variables spanning 7 domains of SDOH, including bias, education, physical and health infrastructure, natural environment, socioeconomic status, social context, and crime and drugs, were studied. Hierarchical agglomerative clustering was used to identify SDOH patterns.

Main outcomes and measures: Associations of SDOH and child mental health (internalizing and externalizing behaviors) and suicidal behaviors, cognitive function (performance, reading skills), and physical health (body mass index, exercise, sleep disorder) were estimated using mixed-effects linear and logistic regression models.

Results: Among 10 504 children (baseline median [SD] age, 9.9 [0.6] years; 5510 boys [52.5%] and 4994 girls [47.5%]; 229 Asian [2.2%], 1468 Black [14.0%], 2128 Hispanic [20.3%], 5565 White [53.0%], and 1108 multiracial [10.5%]), 4 SDOH patterns were identified: pattern 1, affluence (4078 children [38.8%]); pattern 2, high-stigma environment (2661 children [25.3%]); pattern 3, high socioeconomic deprivation (2653 children [25.3%]); and pattern 4, high crime and drug sales, low education, and high population density (1112 children [10.6%]). The SDOH patterns were distinctly associated with child health outcomes. Children exposed to socioeconomic deprivation (SDOH pattern 3) showed the worst health profiles, manifesting more internalizing (β = 0.75; 95% CI, 0.14-1.37) and externalizing (β = 1.43; 95% CI, 0.83-2.02) mental health problems, lower cognitive performance, and adverse physical health.

Conclusions: This study shows that an unbiased quantitative analysis of multidimensional SDOH can permit the determination of how SDOH patterns are associated with child developmental outcomes. Children exposed to socioeconomic deprivation showed the worst outcomes relative to other SDOH categories. These findings suggest the need to determine whether improvement in socioeconomic conditions can enhance child developmental outcomes.

Luo S, Hsu E, Lawrence KE, Adise S, Pickering TA, Herting MM, Buchanan T, Page KA, Thompson PM. Associations among prenatal exposure to gestational diabetes mellitus, brain structure, and child adiposity markers. Obesity (Silver Spring). 2023 Oct 16. doi: 10.1002/oby.23901. Epub ahead of print. PMID: 37840377.

Objective: The aim of this study was to investigate the mediating role of child brain structure in the relationship between prenatal gestational diabetes mellitus (GDM) exposure and child adiposity.

Methods: This was a cross-sectional study of 9- to 10-year-old participants and siblings across the US. Data were obtained from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study®. Brain structure was evaluated by magnetic resonance imaging. GDM exposure was self-reported, and discordance for GDM exposure within biological siblings was identified. Mixed effects and mediation models were used to examine associations among prenatal GDM exposure, brain structure, and adiposity markers with sociodemographic covariates.

Results: The sample included 8521 children (7% GDM-exposed), among whom there were 28 sibling pairs discordant for GDM exposure. Across the entire study sample, prenatal exposure to GDM was associated with lower global and regional cortical gray matter volume (GMV) in the bilateral rostral middle frontal gyrus and superior temporal gyrus. GDM-exposed siblings also demonstrated lower global cortical GMV than unexposed siblings. Global cortical GMV partially mediated the associations between prenatal GDM exposure and child adiposity markers.

Conclusions: The results identify brain markers of prenatal GDM exposure and suggest that low cortical GMV may explain increased obesity risk for offspring prenatally exposed to GDM.

McCarthy MJ, Brumback T, Thomas ML, Meruelo, AD. The relations between chronotype, stressful life events, and impulsivity in the adolescent brain cognitive development (ABCD) study. Journal of Psychiatric Research. Available online 16 October 2023. https://doi.org/10.1016/j.jpsychires.2023.10.030.

Circadian rhythm disturbances, especially circadian phase delays are associated with impulsive behaviors and have been implicated in psychiatric disorders. Chronotype is a developmentally regulated proxy measure of circadian phase. Past studies have investigated the relationship between chronotype and trauma and found that trauma is associated with evening chronotypes, suggesting the course of chronotype development may be affected by adverse childhood experiences (ACEs). However, the relationships among chronotype, impulsivity and ACEs have largely been studied in a pairwise manner using small, cross-sectional cohorts. We hypothesized that in a cohort of high-risk youth, childhood trauma would be associated with later chronotype, and later chronotype would be associated with higher rates of impulsivity. We analyzed a cross-sectional sample (n = 966) from Year 2 of adolescents at high risk for psychiatric disorders from the ABCD study who were characterized for chronotype, stressful life events, and impulsivity. We used a hierarchical regression model to examine the relationship between chronotype, stressful life events, and impulsivity using the Munich Chronotype Questionnaire (MCTQ), the Life Events Scale, Urgency, Premeditation, Perseverance and Sensation Seeking (UPPS) Impulsive Behavior scale. We found associations between eveningness, stressful life events, and all dimensions of impulsivity. Increased eveningness was associated with a higher number of stressful life events and increased impulsivity. Understanding the role of stressful life events and impulsivity in those predisposed towards eveningness is useful because it may improve our understanding of the biological mechanisms that contribute to psychiatric disorders, and lead to better prevention and treatment efforts using interventions such as increased lifestyle regularity and daytime light exposure.

Adise S, Boutelle KN, Rezvan PH, Kan E, Rhee KE, Goran MI, Sowell ER. Sex-specific impulsivity, but not other facets of executive functioning, predicts fat and sugar intake two-years later amongst adolescents with a healthy weight: Findings from the ABCD study. Appetite. 2023 Oct 13:107081. doi: 10.1016/j.appet.2023.107081. Epub ahead of print. PMID: 37839556.

During adolescence processes that control food intake (executive functions [EF]) undergo extensive refinement; underlying differences in EF may explain the inability to resist overeating unhealthy foods. Yet, overeating fat and sugar also causes changes to EF and cognition but disentangling these relationships has been difficult, as previous studies included youth with obesity. Here, amongst youth initially of a healthy weight, we evaluate whether 1) sex-specific underlying variation in EF/cognition at 9/10-years-old predict fat/sugar two-years later (Y2) and 2) if these relationships are moderated by body mass index (BMI), using linear mixed effects models (controlled for puberty, caregiver education; random effect: study site). Data were leveraged from Adolescent Brain Cognitive Development Study (n = 2987; 50.4% male; 15.4% Latino/a/x; 100% healthy weight at baseline; 12.4% overweight/obese by Y2, data release 4.0). EF and cognition (e.g., inhibition, impulsivity, cognition, motor, memory) were assessed with the NIH toolbox, Rey Auditory Verbal Listening Test, Little Man Task, the BIS/BAS, and UPPS-P. A saturated fat/added sugar (kcals) composite score was extracted from the validated Kids Food Block Screener. For males, greater baseline impulsivity (e.g., Positive Urgency, Lack of Planning and Perseverance) and reward (e.g., Fun seeking, Drive) was related to greater Y2 intake. For both sexes, greater baseline Negative Urgency and higher BMI was related to greater Y2 intake. No other relationships were observed. Our findings highlight a phenotype that may be more at risk for weight gain due to overconsumption of fat/sugar. Thus, prevention efforts may wish to focus on impulsive tendencies for these foods.

Nagata JM, Smith-Russack Z, Paul A, Saldana GA, Shao IY, Al-Shoaibi AAA, Chaphekar AV, Downey AE, He J, Murray SB, Baker FC, Ganson KT. The social epidemiology of binge-eating disorder and behaviors in early adolescents. J Eat Disord. 2023 Oct 13;11(1):182. doi: 10.1186/s40337-023-00904-x. PMID: 37833810; PMCID: PMC10571438.

Background: Binge-eating disorder (BED) is the most common eating disorder phenotype and is linked to several negative health outcomes. Yet, little is known about the social epidemiology of BED, particularly in early adolescence. The objective of this study was to examine the associations between sociodemographic characteristics and BED and binge-eating behaviors in a large, national cohort of 10-14-year-old adolescents in the United States (U.S.) METHODS: We conducted a cross-sectional analysis of two-year follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study (2018 – 2020) that included 10,197 early adolescents (10 – 14 years, mean 12 years) in the U.S. Multivariable logistic regression models were used to assess the associations between sociodemographic characteristics and BED and binge-eating behaviors, defined based on the Kiddie Schedule for Affective Disorders and Schizophrenia.

Results: In this early adolescent sample (48.8% female, 54.0% White, 19.8% Latino/Hispanic, 16.1% Black, 5.4% Asian, 3.2% Native American, 1.5% Other), the prevalence of BED and binge-eating behaviors were 1.0% and 6.3%, respectively. Identifying as gay or bisexual (compared to heterosexual; adjusted odds ratio [AOR]: 2.25, 95% CI 1.01-5.01) and having a household income of less than $75,000 (AOR: 2.05, 95% CI: 1.21-3.46) were associated with greater odds of BED. Being male (AOR: 1.28, 95% CI: 1.06-1.55), of Native American (AOR: 1.60, 95% CI: 1.01-2.55) descent, having a household income less than $75,000 (AOR: 1.34, 95% CI: 1.08-1.65), or identifying as gay or bisexual (AOR for ‘Yes’ Response: 1.95, 95% CI: 1.31-2.91 and AOR for ‘Maybe’ Response: 1.81, 95% CI: 1.19-2.76) were all associated with higher odds of binge-eating behaviors.

Conclusion: Several sociodemographic variables showed significant associations with binge-eating behaviors, which can inform targeted screening, prevention, and education campaigns for BED among early adolescents.

Ward J, Lyall LM, Cullen B, Strawbridge RJ, Zhu X, Stanciu I, Aman A, Niedzwiedz CL, Anderson J, Bailey MES, Lyall DM, Pell JP. Consistent effects of the genetics of happiness across the lifespan and ancestries in multiple cohorts. Sci Rep. 2023 Oct 12;13(1):17262. doi: 10.1038/s41598-023-43193-9. PMID: 37828061; PMCID: PMC10570373.

Happiness is a fundamental human affective trait, but its biological basis is not well understood. Using a novel approach, we construct LDpred-inf polygenic scores of a general happiness measure in 2 cohorts: the Adolescent Brain Cognitive Development (ABCD) cohort (N = 15,924, age range 9.23-11.8 years), the Add Health cohort (N = 9129, age range 24.5-34.7) to determine associations with several well-being and happiness measures. Additionally, we investigated associations between genetic scores for happiness and brain structure in ABCD (N = 9626, age range (8.9-11) and UK Biobank (N = 16,957, age range 45-83). We detected significant (p.FDR < 0.05) associations between higher genetic scores vs. several well-being measures (best r2 = 0.019) in children of multiple ancestries in ABCD and small yet significant correlations with a happiness measure in European participants in Add Health (r2 = 0.004). Additionally, we show significant associations between lower genetic scores for happiness with smaller structural brain phenotypes in a white British subsample of UK Biobank and a white sub-sample group of ABCD. We demonstrate that the genetic basis for general happiness level appears to have a consistent effect on happiness and wellbeing measures throughout the lifespan, across multiple ancestral backgrounds, and multiple brain structures.

Peltz J, Zhang L, Sasser J, Oshri A, Doane LD. The Influence of Pubertal Development on Early Adolescent Sleep and Changes in Family Functioning. J Youth Adolesc. 2023 Oct 10. doi: 10.1007/s10964-023-01882-8. Epub ahead of print. PMID: 37816912.

Pubertal development has been separately linked to adolescents’ sleep problems and larger family functioning, but research connecting these inter-related processes remains sparse. This study aimed to examine how pubertal status and tempo were related to early adolescents’ sleep and their family functioning. Using longitudinal data from the Adolescent Brain and Cognitive Development study, the study’s sample (N = 4682) was 49.2% female, was an average of 9.94 years old at baseline, and was 60.1% white. Analyses in the current study modeled the indirect associations between pubertal change and changes in family conflict via adolescent sleep duration and variability of duration. The results suggested that pubertal status and tempo predicted shorter adolescent sleep durations and greater variability in those durations, which predicted residual increases in family conflict. The findings highlight the role of adolescents’ pubertal changes in their sleep and how such changes can negatively affect family functioning.

Vedechkina M, Holmes J. Cognitive difficulties following adversity are not related to mental health: Findings from the ABCD study. Dev Psychopathol. 2023 Oct 10:1-14. doi: 10.1017/S0954579423001220. Epub ahead of print. PMID: 37815218.

Early life adversity is associated with differences in cognition and mental health that can impact on daily functioning. This study uses a hybrid machine-learning approach that combines random forest classification with hierarchical clustering to clarify whether there are cognitive differences between individuals who have experienced moderate-to-severe adversity relative to those have not experienced adversity, to explore whether different forms of adversity are associated with distinct cognitive alterations and whether these such alterations are related to mental health using data from the ABCD study (n = 5,955). Cognitive measures spanning language, reasoning, memory, risk-taking, affective control, and reward processing predicted whether a child had a history of adversity with reasonable accuracy (67%), and with good specificity and sensitivity (>70%). Two subgroups were identified within the adversity group and two within the no-adversity group that were distinguished by cognitive ability (low vs high). There was no evidence for specific associations between the type of adverse exposure and cognitive profile. Worse cognition predicted lower levels of mental health in unexposed children. However, while children who experience adversity had elevated mental health difficulties, their mental health did not differ as a function of cognitive ability, thus providing novel insight into the heterogeneity of psychiatric risk.

Elsayed NM, Barch DM. B – 11 Early Life Traumatic Brain Injury Constrains the Benefits of High Socioeconomic Status on White Matter Microstructure and Language. Arch Clin Neuropsychol. 2023 Oct 8:acad067.218. doi: 10.1093/arclin/acad067.218. Epub ahead of print. PMID: 37807401.

Objective: We examined contributions of socioeconomic status (SES) and Traumatic Brain Injury (TBI) to change in language and white matter microstructure (WMM) during adolescence.

Method: Data are from 11,876 youth with baseline assessment (T1) and 24-month follow-up (T2) in the Adolescent Brain Cognitive Development study (general community sample). TBI data were from the parent-reported Ohio State TBI Identification Method. Language was measured using the NIH-toolbox picture-vocabulary test. TBI cases, with complete data, were nearest-neighbor propensity score matched with non-TBI cases considering handedness, income, race, age, sex, and diffusion tensor imaging quality (N-analyses = 141). WMM in the uncinate fasciculus (UF) was assessed using fractional anisotropy (FA). Analyses were conducted using nested linear models accounting for dependencies, age, sex, and handedness.

Results: TBI was not independently associated with language or WMM at T1 (mean age in months (MA) = 118.8) or T2 (MA = 142.8) (all p > 0.05). TBI and SES interacted in association with T1 UF-FA (p = 0.03, CI = -0.05, -0.02). Low SES youth did not differ in T1 UF-FA. Among high SES youth, those without TBI had higher UF-FA (p = 0.04). A 3-way interaction between SES, TBI and change in UF-FA between T1 and T2 in predicting language emerged (p = 0.01, CI = 0.12, 1.06). Youth with moderate-to-high levels of UF change did not differ in language. For youth with low increases in UF, SES and language were positively associated only in youth without TBI (p = 0.0003).

Conclusion(s): TBI does not have a direct effect on adolescent WMM or language but interacts with SES and WMM to blunt benefit of SES on language.

Agarwal K, Manza P, Tejeda HA, Courville AB, Volkow ND, Joseph PV. Risk Assessment of Maladaptive Behaviors in Adolescents: Nutrition, Screen Time, Prenatal Exposure, Childhood Adversities – Adolescent Brain Cognitive Development Study. J Adolesc Health. 2023 Oct 7:S1054-139X(23)00443-3. doi: 10.1016/j.jadohealth.2023.08.033. Epub ahead of print. PMID: 37804305.

Purpose: We aimed to identify significant contributing factors to the risk of maladaptive behaviors, such as alcohol use disorder or obesity, in children. To achieve this, we utilized the extensive adolescent brain cognitive development data set, which encompasses a wide range of environmental, social, and nutritional factors.

Methods: We divided our sample into equal sets (test, validation; n = 3,415 each). On exploratory factor analysis, six factor domains were identified as most significant (fat/sugar intake, screen time, and prenatal alcohol exposure, parental aggressiveness, hyperactivity, family violence, parental education, and family income) and used to stratify the children into low- (n = 975), medium- (n = 967), high- (n = 977) risk groups. Regression models were used to analyze the relationship between identified risk groups, and differences in reward sensitivity, and behavioral problems at 2-year follow-up.

Results: The functional magnetic resonance imaging analyses showed reduced activation in several brain regions during reward or loss anticipation in high/medium-risk (vs. low-risk) children on a monetary incentive delay task. High-risk children exhibited heightened middle frontal cortex activity when receiving large rewards. They also displayed increased impulsive and motivated reward-seeking behaviors, along with behavioral problems. These findings replicated in our validation set, and a negative correlation between middle frontal cortexthickness and impulsivity behavior was observed in high-risk children.

Discussion: Our findings show altered reward function and increased impulsiveness in high-risk adolescents. This study has implications for early risk identification and the development of prevention strategies for maladaptive behaviors in children, particularly those at high risk.

Correa KA, Delfel EL, Wallace AL, Iii WEP, Jacobus J. Hispanic/Latinx ethnic differences in the relationships between behavioral inhibition, anxiety, and substance use in youth from the ABCD cohort. Front Psychiatry. 2023 Oct 6;14:1251032. doi: 10.3389/fpsyt.2023.1251032. PMID: 37867762; PMCID: PMC10587569.

Introduction: Elevated levels of behavioral inhibition (BI) may connote risk for both anxiety and substance use disorders. BI has consistently been shown to be associated with increased levels of anxiety, while the association between BI and substance use has been mixed. It is possible that the relationship between BI and substance use varies by individual difference factors. Hispanic/Latinx (H/L) youth in particular may have stronger relationships between BI, anxiety, and substance use.

Methods: The present study therefore evaluated (1) the prospective relationships between BI [assessed via self-reported behavioral inhibition system (BIS) scale scores], anxiety, and substance use in youth (n = 11,876) across baseline, 1-, and 2-year follow-ups of the Adolescent Brain Cognitive Development (ABCD) Study (ages 9-12) and (2) whether these relationships differed by H/L ethnicity while covarying for average behavioral approach system scores, race, sex, age, highest parental income, highest parental education, and past-year substance use (for analyses involving substance use outcomes).

Results: Baseline levels of BIS scores predicted increased anxiety symptoms at both 1- and 2-year follow-ups and did not differ by H/L ethnicity. Baseline levels of BIS scores also prospectively predicted increased likelihood of substance use at 2-year follow-up, but only for H/L youth and not at 1-year follow-up.

Discussion: High scores on the BIS scale contribute risk to anxiety across ethnicities and may uniquely contribute to risk for substance use in H/L youth.

Ma Q, Cui Y, Han X, Xiong Y, Xu J, Zhao H, Li X, Cheng W, Zhou Q. Association of maternal hypertension during pregnancy with brain structure and behavioral problems in early adolescence. Eur Child Adolesc Psychiatry. 2023 Oct 6. doi: 10.1007/s00787-023-02305-6. Epub ahead of print. PMID: 37803213.

Emerging evidence suggests an association between maternal hypertension during pregnancy and mental health in the offspring. However, less is known about the role of hypertensive pregnancy in behavioral symptoms and brain structures of the offspring as well as in their developmental changes. Here, we utilized neuroimaging and behavioral data from 11,878 participants aged 9-10 years and their 2-year follow-up from the Adolescent Brain Cognitive Development (ABCD) study to investigate the long-term effects of maternal hypertension during pregnancy on early adolescent behavior and brain anatomy. Specifically, adolescents born of mothers with maternal hypertension are at risk of long-lasting behavioral problems, as manifested by higher externalizing and internalizing behavior scores at both 9-10 years and 11-12 years. These participants additionally presented with a higher cortical thickness, particularly in the fronto-parieto-temporal areas at 9-10 years. Four regions, including the left parahippocampus, left lateral orbitofrontal lobe, right superior temporal lobe and right temporal pole, remained thicker 2 years later. These findings were partially validated in rats modeled with Nω-nitro-L-arginine methyl ester (L-NAME) preeclampsia. Therefore, clinicians and women who experience hypertension during pregnancy should be warned of this risk, and healthcare providers should recommend appropriate clinical interventions for pregnancy-induced hypertension.

Trevino AD, Jamil B, Su J, Aliev F, Elam KK, Lemery-Chalfant K. Alcohol Use Disorder Polygenic Risk Scores and Trajectories of Early Adolescent Externalizing Behaviors: Examining the Role of Parenting and Family Conflict in the Racially/Ethnically Diverse ABCD Sample. Behav Genet. 2023 Oct 4. doi: 10.1007/s10519-023-10155-w. Epub ahead of print. PMID: 37792148.

This study examined the independent and interactive effects of alcohol use disorder genome-wide polygenic scores (AUD-PGS) and parenting and family conflict on early adolescent externalizing behaviors. Data were drawn from White (N = 6181, 46.9% female), Black/African American (N = 1784, 50.1% female), and Hispanic/Latinx (N = 2410, 48.0% female) youth from the adolescent brain cognitive development Study (ABCD). Parents reported on youth externalizing behaviors at baseline (T1, age 9/10), 1-year (T2, age 10/11) and 2-year (T3, age 11/12) assessments. Youth reported on parenting and family environment at T1 and provided saliva or blood samples for genotyping. Results from latent growth models indicated that in general externalizing behaviors decreased from T1 to T3. Across all groups, higher family conflict was associated with more externalizing behaviors at T1, and we did not find significant associations between parental monitoring and early adolescent externalizing behaviors. Parental acceptance was associated with lower externalizing behaviors among White and Hispanic youth, but not among Black youth. Results indicated no significant main effect of AUD-PGS nor interaction effect between AUD-PGS and family variables on early adolescent externalizing behaviors. Post hoc exploratory analysis uncovered an interaction between AUD-PGS and parental acceptance such that AUD-PGS was positively associated with externalizing rule-breaking behaviors among Hispanic youth, but only when parental acceptance was very low. Findings highlight the important role of family conflict and parental acceptance in externalizing behaviors among early adolescents, and emphasize the need to examine other developmental pathways underlying genetic risk for AUD across diverse populations.

Luciana M, Barch D, Herting MM. Adolescent brain cognitive development study: Longitudinal methods, developmental findings, and associations with environmental risk factors. Dev Cogn Neurosci. 2023 Oct 4:101311. doi: 10.1016/j.dcn.2023.101311. Epub ahead of print. PMID: 37827934.

Damme K, Vargas T, Walther S, Shankman S, Mittal V. Physical and Mental Health in Adolescence: Novel Insights from a transdiagnostic examination of FitBit data in the ABCD Study. Res Sq [Preprint]. 2023 Oct 3:rs.3.rs-3270112. doi: 10.21203/rs.3.rs-3270112/v1. PMID: 37886441; PMCID: PMC10602093.

Adolescence is among the most vulnerable period for the emergence of serious mental illnesses. Addressing this vulnerability has generated interest in identifying markers of risk for symptoms and opportunities for early intervention. Physical fitness has been linked to psychopathology and may be a useful risk marker and target for early intervention. New wearable technology has made assessing fitness behavior more practical while avoiding recall and self-report bias. Still, questions remain regarding the clinical utility of physical fitness metrics for mental health, both transdiagnostically and along specific symptom dimensions. The current study includes 5007 adolescents (ages 10 to 13) who participated in the Adolescent Brain Cognitive Development (ABCD) study and additional sub-study that collected fitness data from wearable technology and clinical symptom measures. Physical fitness metrics included resting heart rate (RHR- an index of cardiovascular health), time spent sedentary (associated with increased inflammation and cardiovascular disease), and time spent in moderate physical activity (associated with increased neurogenesis, neuroplasticity, and healthy neurodevelopment). Self-report clinical symptoms included measures of internalizing symptoms, externalizing symptoms, and psychosis-like experiences – PLE). Increased RHR- lower cardiovascular fitness- related only to greater internalizing symptoms (t = 3.63). More sedentary behavior related to elevated PLE severity (t = 5.49). More moderate activity related to lower PLE (t=-2.69) and internalizing (t=-6.29) symptom severity. Wearable technology fitness metrics linked physical health to specific mental health dimensions, which emphasizes the utility of detailed digital health data as a marker for risk and the need for precision in targeting physical health behaviors to benefit symptoms of psychopathology.

Senger-Carpenter T, Seng J, Herrenkohl TI, Marriott D, Chen B, Voepel-Lewis T. Applying Life History Theory to Understand Earlier Onset of Puberty: An Adolescent Brain Cognitive Development Cohort Analysis. J Adolesc Health. 2023 Oct 3:S1054-139X(23)00423-8. doi: 10.1016/j.jadohealth.2023.08.013. Epub ahead of print. PMID: 37791924.

Purpose: Life history theory posits that multigenerational exposure to adversity and deprivation influences childhood growth and development, including pubertal maturation. We applied this ecological, evolutionary theory to examine the contributions of distal and proximal adversity on early puberty, a potentially important marker for population health.

Methods: Baseline data from 5,645 girls in the adolescent brain cognitive development study were included. Early puberty was defined as midlate/post pubertal development by age 9-11 years. The contributions of multigenerational Black/Indigenous (Black, Indigenous and People of Color [BIPOC]) or Hispanic identities, intergenerational mental health, economic deprivation, personal trauma exposure and mental health, and proximal biological factors of premature birth and body mass index on early puberty were examined with hierarchical modeling.

Results: 1,225 girls (21.7%) had early puberty. BIPOC/Hispanic identity, familial adversity, economic deprivation, personal trauma, depression, and a higher body mass index contributed significantly toward early puberty. The effect of multigenerational adversity remained significant across models, but the likelihood of early puberty decreased sequentially for BIPOC and Hispanic youth as proximal adversities were added (e.g., OR decreased from 2.93 to 2.38 for BIPOC youth), supporting a synergistic effect of layered adversity on early puberty.

Discussion: This analysis supports life history theory as a coherent framework to understand early puberty among girls. Findings suggest monitoring pubertal timing as a population health indictor, like birth weight, prematurity, or life expectancy. Addressing early puberty may require policy and social changes to mitigate the negative impact of multiple layers of adversity including racial/ethnic disadvantage, family, and individual mental health and trauma, as well as economic insecurity.

Yang FN, Picchioni D, Duyn JH. Effects of sleep-corrected social jetlag on measures of mental health, cognitive ability, and brain functional connectivity in early adolescence. Sleep. 2023 Oct 3:zsad259. doi: 10.1093/sleep/zsad259. Epub ahead of print. PMID: 37788383.

Approximately half of adolescents encounter a mismatch between their sleep patterns on school days and free days, also referred to as “social jetlag”. This condition has been linked to various adverse outcomes, such as poor sleep, cognitive deficits, and mental disorders. However, prior research was unsuccessful in accounting for other variables that are correlated with social jetlag, including sleep duration and quality. To address this limitation, we applied a propensity score matching method on a sample of 6335 11-12-year-olds from the two-year follow-up (FL2) data of the Adolescent Brain Cognitive Development (ABCD) study. We identified 2424 pairs of participants with high sleep-corrected social jetlag (SJLsc, over 1 hour) and low SJLsc (<= 1 hour) at FL2 (1728 pairs have neuroimaging data), as well as 1626 pairs at three-year follow-up (FL3), after matching based on 11 covariates including socioeconomic status, demographics, and sleep duration and quality. Our results showed that high SJLsc, as measured by the Munich Chronotype Questionnaire, was linked to reduced crystallized intelligence, lower school performance – grades, and decreased functional connectivity between cortical networks and subcortical regions, specifically between cingulo-opercular network and right hippocampus. Further mediation and longitudinal mediation analyses revealed that this connection mediated the associations between SJLsc and crystallized intelligence at FL2, and between SJLsc and grades at both FL2 and FL3. We validated these findings by replicating these results using objective SJLsc measurements obtained via Fitbit watches. Overall, our study highlights the negative association between social jetlag and crystallized intelligence during early adolescence.

Evanski JM, Zundel CG, Baglot SL, Desai S, Gowatch LC, Ely SL, Sadik N, Lundahl LH, Hill MN, Marusak HA. The First “Hit” to the Endocannabinoid System? Associations Between Prenatal Cannabis Exposure and Frontolimbic White Matter Pathways in Children. Biol Psychiatry Glob Open Sci. 2023 Sep 30;4(1):11-18. doi: 10.1016/j.bpsgos.2023.09.005. PMID: 38021250; PMCID: PMC10654001.

Background: Cannabis is the most used federally illicit substance among pregnant people in the United States. However, emerging preclinical data show that a significant portion of cannabis constituents, such as Δ9-tetrahydrocannabinol and its bioactive metabolites, readily cross the placenta and accumulate in the fetal brain, disrupting neurodevelopment. Recent research using the Adolescent Brain Cognitive Development (ABCD) Study cohort has linked prenatal cannabis exposure (PCE) to greater neurobehavioral problems and lower total gray and white matter volume in children. Here, we examined the impact of PCE on frontolimbic white matter pathways that are critical for cognitive- and emotion-related functioning, show a high density of cannabinoid receptors, and are susceptible to cannabis exposure during other periods of rapid neurodevelopment (e.g., adolescence).

Methods: This study included 11,530 children (mean ± SD age = 118.99 ± 7.49 months; 47% female) from the ABCD Study cohort. Linear mixed-effects models were used to examine the effects of caregiver-reported PCE on fractional anisotropy of 10 frontolimbic pathways (5 per hemisphere).

Results: PCE was associated with lower fractional anisotropy of the right (β = -0.005, p < .001) and left (β = -0.003, p = .007) fornix, and these results remained significant after adjusting for a variety of covariates, multiple comparisons, fractional anisotropy of all fibers, and using a quality-control cohort only.

Conclusions: In sum, we demonstrated small, yet reliable, effects of PCE on white matter integrity during childhood, particularly in the fornix, which plays a crucial role in emotion- and memory-related processes. Future studies are needed to understand the impacts of small changes in brain structure or function on neurodevelopment and risk of neurobehavioral problems.

Bounoua N, Church LD, Matyi MA, Rudoler J, Wieand K, Spielberg JM. Assessing the utility of a novel cortical marker of delay discounting (C-DD) in two independent samples of early adolescents: Links with externalizing pathology. PLoS One. 2023 Sep 27;18(9):e0291868. doi: 10.1371/journal.pone.0291868. PMID: 37756262.

Delay discounting is a well-established risk factor for risky behaviors and the development of externalizing spectrum disorders. Building upon recent work that developed a novel cortical marker of delay discounting (C-DD) in adult samples, the objective of this study was to test whether the C-DD relates to delay discounting and subsequently externalizing pathology in adolescent samples. The current study used two samples: 9992 early adolescents participating in the ABCD study (Mage = 9.93 years old, 48.7% female), and 56 early adolescents recruited from the community (Mage = 12.27 years old, 55.4% female). Cortical thickness was estimated using the FreeSurfer standard pipeline, and the cortical marker of delay discounting (C-DD) was calculated based on procedures outlined by the initial validation study. All data are cross-sectional in nature. As expected, C-DD was positively related to delay discounting in the ABCD sample, even after accounting for age, biological sex, collection site and data quality indicators. Moreover, results showed that C-DD was discriminately associated with externalizing, but not internalizing, symptoms in both samples of young adolescents. Findings replicate those found in adult samples, suggestive that C-DD may be a useful neuroanatomical marker of youth delay discounting. Replication of findings in other samples will be needed to determine whether C-DD has translational relevance to understanding externalizing psychopathology in adolescent samples.

Yan W, Pearlson GD, Fu Z, Li X, Iraji A, Chen J, Sui J, Volkow ND, Calhoun VD. A brain-wide risk score for psychiatric disorder evaluated in a large adolescent population reveals increased divergence among higher-risk groups relative to controls. Biol Psychiatry. 2023 Sep 26:S0006-3223(23)01592-5. doi: 10.1016/j.biopsych.2023.09.017. Epub ahead of print. PMID: 37769983.

Background: Accurate psychiatric risk assessment requires biomarkers that are both stable and adaptable to development. Functional network connectivity (FNC), which steadily reconfigures over time, potentially contains abundant information to assess psychiatric risks. However, the absence of suitable analytical methodologies has constrained this area of investigation.

Methods: We investigated brain-wide risk score (BRS), a novel FNC-based metric that contrasts the relative distances of an individual’s FNC to that of psychiatric disorders versus healthy control references. To generate group-level disorder and healthy control references, we utilized a large brain imaging dataset containing 5231 total individuals diagnosed with schizophrenia, autism spectrum, major depressive, and bipolar disorders, and their corresponding healthy controls. The BRS metric was employed to assess the psychiatric risk in two new datasets: Adolescent Brain and Cognitive Development (ABCD, N=8191) and Human Connectome Project Early Psychosis (HCP-EP, N=170).

Results: The BRS revealed clear, reproducible gradient of FNC patterns from low-to-high-risk for each psychiatric disorder in unaffected adolescents. We found that low-risk ABCD adolescent FNC patterns for each disorder were strongly present in over 25% of the ABCD subjects and homogeneous, whereas high-risk patterns of each psychiatric disorder were strongly present in about 1% of ABCD subjects and heterogeneous. The BRS also showed its effectiveness in predicting psychosis scores and distinguishing individuals with early psychosis from healthy controls.

Conclusions: The BRS could be a new image-based tool for assessing psychiatric vulnerability over time and in unaffected individuals, and it could also serve as a potential biomarker, facilitating early screening and monitoring interventions.

Xiao X, Hammond C, Salmeron BJ, Wang D, Gu H, Zhai T, Nguyen H, Lu H, Ross TJ, Yang Y. Brain Functional Connectome Defines a Transdiagnostic Dimension Shared by Cognitive Function and Psychopathology in Preadolescents. Biol Psychiatry. 2023 Sep 26:S0006-3223(23)01593-7. doi: 10.1016/j.biopsych.2023.08.028. Epub ahead of print. PMID: 37769982.

Background: Cognitive function and general psychopathology are two important classes of human behavior dimensions, individually relate to mental disorders across diagnostic categories. However, whether the two transdiagnostic dimensions link to common or distinct brain networks that convey resilience or risk for the development of psychiatric disorders remains unclear.

Method: The current study is a longitudinal investigation with 11,875 youths aged 9- to 10-years-old at study onset, from the Adolescent Brain Cognitive Development study. A machine-learning approach based on canonical correlation analysis was used to identify latent dimensional associations of the resting-state functional connectome with multi-domain behavioral assessments including cognitive functions and psychopathological measures. For the latent rsFC factor showing a robust behavioral association, its ability to predict psychiatric disorders was assessed using two-year follow-up data and its genetic association was evaluated using twin data from the same cohort.

Results: A latent functional connectome pattern was identified that showed a strong and generalizable association with the multi-domain behavioral assessments (5-fold cross validation: ρ = 0.68∼0.73, for the training set (N = 5096); ρ = 0.56 ∼ 0.58, for the test set (N = 1476)). This functional connectome pattern was highly heritable (h2 = 74.42%, 95% CI: 56.76%-85.42%), exhibited a dose-response relationship with cumulative number of psychiatric disorders assessed concurrently and 2-years post-MRI-scan, and predicted the transition of diagnosis across disorders over the 2-year follow-up period.

Conclusion: These findings provide preliminary evidence for a transdiagnostic connectome-based measure that underlies individual differences in developing psychiatric disorders in early adolescence.

Shao IY, Yang J, Ganson KT, Baker FC, Nagata JM. Identification and characterization of screen use trajectories from late childhood to adolescence in a US-population based cohort study. Prev Med Rep. 2023 Sep 21;36:102428. doi: 10.1016/j.pmedr.2023.102428. PMID: 37766729; PMCID: PMC10520867./

Screen use is a known risk factor for adverse physical and mental health outcomes during childhood and adolescence. Moreover, racial/ethnic disparity in screen use persists among adolescents. However, limited studies have characterized the population sharing similar longitudinal patterns of screen use from childhood to adolescence. This study will identify and characterize the subgroups of adolescents sharing similar trajectories of screen use from childhood to adolescence. Study participants of the Adolescent Brain Cognitive Development Study (2016-2021) in the U.S with non-missing responses on self-reported screen use at each year of the study were included in the analysis. Growth mixture modeling was used to identify the optimal number of subgroups of adolescents with similar trajectories. Subsequently, socio-demographic characteristics, familial background, and perceived racism and discrimination during childhood was assessed for each subgroup population. Perceived discrimination was measured using the Perceived Discrimination Scale. There were two major subgroups of individuals sharing similar trajectories of screen use: Drastically Increasing group (N = 1333); Gradually Increasing group (N = 10336). Higher proportions of the Drastically Increasing group were racial/ethnic minorities (70%) as compared to the Gradually Increasing group (45%). Moreover, the Drastically Increasing group had higher proportions of individuals reporting perceived racism and discrimination during childhood.

Peisch V, Li V, Arnett AB. Effortful Control Protects Against Familial Liability for ADHD: Longitudinal Results from the ABCD Study in the United States. Res Child Adolesc Psychopathol. 2023 Sep 26. doi: 10.1007/s10802-023-01131-3. Epub ahead of print. PMID: 37750998.

Effortful control, the ability to regulate complex and goal-directed behavior, may protect individuals from developing mental health symptoms. This study tested the potential for child effortful control and executive functioning to buffer the effects of familial liability for attention deficit hyperactivity disorder (ADHD) problems across a one-year timeframe. Data from the prospectively-collected Adolescent Brain Cognitive Development (ABCD)® study were used to examine whether caregiver-rated child effortful control and executive functioning moderated the association between familial ADHD risk and later ADHD symptoms in a sample of children (N = 6,133; ages 9-10 years at baseline). Two independent variables were considered to compare the predictive powers of specific (family ADHD) and broad (family psychopathology) risk factors. Two additional moderating variables (surgency, negative affect) were tested to examine specificity of effortful control and executive functioning as moderators. All variables of interest were measured on a continuum and via caregiver report. At high levels of effortful control and executive functioning, there was no association between familial liability for ADHD or broad psychopathology and later child ADHD problems. The moderator effects were specific to effortful control and executive functioning domains. Etiological models of heritable psychiatric disorders, such as ADHD, should consider the risk and protective contributions of individual traits, such as effortful control and executive functioning. Clinical prevention and intervention efforts may target self-regulation skills in children to buffer against familial liability for ADHD problems.

Lewis-de Los Angeles WW. Adverse childhood experiences and accelerometer-measured physical activity and sleep in pre-adolescents. Acad Pediatr. 2023 Sep 23:S1876-2859(23)00364-9. doi: 10.1016/j.acap.2023.09.014. Epub ahead of print. PMID: 37748537.

Objective: To assess the relationship between adverse childhood experiences (ACEs) and objective measures of physical activity and sleep.

Methods: Data from the baseline and two-year follow-up of the adolescent brain and cognitive development (ABCD) study were analyzed (n = 6227 for physical activity; n=4151 for sleep). ACEs were assessed by parent report at baseline (mean age 9.9 years) with three levels: none, exposure to one ACE, and exposure to two or more ACEs. Objective measures of physical activity and sleep were assessed with an accelerometer at two-year follow-up (mean age 11.9 years). Multivariate linear regression analyses were used to examine the relationship between ACEs and physical activity as well as sleep, adjusting for family income and sex.

Results: Compared to children with no ACEs, children with ACEs had fewer daily steps: one ACE (β =-323 (95% CI: -508 to -138), p<0.001) and two or more ACEs (β=-417 (95% CI: -624 to -209), p<0.001). ACEs were also associated with shorter sleep duration (minutes), although only for participants with two or more ACEs (one ACE: β=-2.2 (-5.3 to 0.8), p=0.16; two or more ACEs: β=-6.2 (95% CI: -9.6 to -2.7), p<0.001). Rapid eye movement (REM) sleep specifically was reduced in participants with ACEs (one ACE (β=-1.4 (-2.7 to -0.01), p=0.05) and two or more ACEs (β=-2.3 (-3.8 to -0.8), p=0.003).

Conclusions: There is a dose response relationship between ACEs and reduced daily steps, total sleep duration, and REM sleep in pre-adolescents.

Fan H, Liu Z, Wu X, Yu G, Gu X, Kuang N, Zhang K, Liu Y, Jia T, Sahakian BJ, Robbins TW, Schumann G, Cheng W, Feng J, Becker B, Zhang J. Decoding anxiety-impulsivity subtypes in preadolescent internalising disorders: findings from the Adolescent Brain Cognitive Development study. Br J Psychiatry. 2023 Sep 21:1-13. doi: 10.1192/bjp.2023.107. Epub ahead of print. PMID: 37730654.

Background: Internalising disorders are highly prevalent emotional dysregulations during preadolescence but clinical decision-making is hampered by high heterogeneity. During this period impulsivity represents a major risk factor for psychopathological trajectories and may act on this heterogeneity given the controversial anxiety-impulsivity relationships. However, how impulsivity contributes to the heterogeneous symptomatology, neurobiology, neurocognition and clinical trajectories in preadolescent internalising disorders remains unclear.

Aims: The aim was to determine impulsivity-dependent subtypes in preadolescent internalising disorders that demonstrate distinct anxiety-impulsivity relationships, neurobiological, genetic, cognitive and clinical trajectory signatures.

Method: We applied a data-driven strategy to determine impulsivity-related subtypes in 2430 preadolescents with internalising disorders from the Adolescent Brain Cognitive Development study. Cross-sectional and longitudinal analyses were employed to examine subtype-specific signatures of the anxiety-impulsivity relationship, brain morphology, cognition and clinical trajectory from age 10 to 12 years.

Results: We identified two distinct subtypes of patients who internalise with comparably high anxiety yet distinguishable levels of impulsivity, i.e. enhanced (subtype 1) or decreased (subtype 2) compared with control participants. The two subtypes exhibited opposing anxiety-impulsivity relationships: higher anxiety at baseline was associated with higher lack of perseverance in subtype 1 but lower sensation seeking in subtype 2 at baseline/follow-up. Subtype 1 demonstrated thicker prefrontal and temporal cortices, and genes enriched in immune-related diseases and glutamatergic and GABAergic neurons. Subtype 1 exhibited cognitive deficits and a detrimental trajectory characterised by increasing emotional/behavioural dysregulations and suicide risks during follow-up.

Conclusions: Our results indicate impulsivity-dependent subtypes in preadolescent internalising disorders and unify past controversies about the anxiety-impulsivity interaction. Clinically, individuals with a high-impulsivity subtype exhibit a detrimental trajectory, thus early interventions are warranted.

Adise S, Ottino-Gonzalez J, Goedde L, Marshall AT, Kan E, Rhee KE, Goran MI, Sowell ER. Variation in executive function relates to BMI increases in youth who were initially of a healthy weight in the ABCD Study. Obesity (Silver Spring). 2023 Sep 20. doi: 10.1002/oby.23811. Epub ahead of print. PMID: 37731207.

Objective: The study aim was to determine whether (A) differences in executive function (EF) and cognition precede weight gain or (B) weight gain causes changes to EF and cognition.

Methods: Data were gathered from the Adolescent Brain Cognitive Development (ABCD) Study (release 4.0; ages 9-12 years old [N = 2794]; 100% had healthy weight at baseline [i.e., 9/10 years old], 12.4% had unhealthy weight by ages 11/12 years). EF and cognition were assessed across several domains (e.g., impulsivity, inhibitory control, processing speed, memory); BMI was calculated from height and weight. Nested random-effects mixed models examined (A) BMI ~ EF × Time (i.e., variation in EF/cognition precedes weight gain) and (B) EF ~ BMI × Time (weight gain causes changes to EF/cognition) and controlled for sex, puberty, and caregiver education; random effects were site and subject.

Results: Variation in impulsivity, memory, learning, and processing speed was associated with greater increases in BMI trajectories from 9 to 12 years old. Weight gain was associated with a decrease in inhibitory control, but no other associations were observed.

Conclusions: Underlying variation in EF and cognition may be important for weight gain, but 2 years of weight gain may not be enough to have clinical implications for EF and cognition beyond inhibitory control. These findings suggest that more attention should be paid to the inclusion of EF programs in obesity prevention efforts.

Newman BT, Patrie JT, Druzgal TJ. An intracellular isotropic diffusion signal is positively associated with pubertal development in white matter. Dev Cogn Neurosci. 2023 Sep 15;63:101301. doi: 10.1016/j.dcn.2023.101301. Epub ahead of print. PMID: 37717292.

Puberty is a key event in adolescent development that involves significant, hormone-driven changes to many aspects of physiology including the brain. Understanding how the brain responds during this time period is important for evaluating neuronal developments that affect mental health throughout adolescence and the adult lifespan. This study examines diffusion MRI scans from the cross-sectional ABCD Study baseline cohort, a large multi-site study containing thousands of participants, to describe the relationship between pubertal development and brain microstructure. Using advanced, 3-tissue constrained spherical deconvolution methods, this study is able to describe multiple tissue compartments beyond only white matter (WM) axonal qualities. After controlling for age, sex, brain volume, subject handedness, scanning site, and sibling relationships, we observe a positive relationship between an isotropic, intracellular diffusion signal fraction and pubertal development across a majority of regions of interest (ROIs) in the WM skeleton. We also observe regional effects from an intracellular anisotropic signal fraction compartment and extracellular isotropic free water-like compartment in several ROIs. This cross-sectional work suggests that changes in pubertal status are associated with a complex response from brain tissue that cannot be completely described by traditional methods focusing only on WM axonal properties.

Sui J, Feng A, Feng Y, Zhi D, Jiang R, Fu Z, Xu M, Zhao M, Yu S, Stevens M, Sun L, Calhoun V. Functional Imaging Derived ADHD Biotypes Based on Deep Clustering May Guide Personalized Medication Therapy. Res Sq [Preprint]. 2023 Sep 14:rs.3.rs-3272441. doi: 10.21203/rs.3.rs-3272441/v1. PMID: 37790426; PMCID: PMC10543279.

Attention deficit hyperactivity disorder (ADHD) is one prevalent neurodevelopmental disorder with childhood onset, however, there is no clear correspondence established between clinical ADHD subtypes and primary medications. Identifying objective and reliable neuroimaging markers for categorizing ADHD biotypes may lead to more individualized, biotype-guided treatment. Here we proposed graph convolutional network plus deep clustering for ADHD biotype detection using functional network connectivity (FNC), resulting in two biotypes based on 1069 ADHD patients selected from Adolescent Brain and Cognitive Development (ABCD) study, which were well replicated on independent ADHD adolescents undergoing longitudinal medication treatment (n=130). Interestingly, in addition to differences in cognitive performance and hyperactivity/impulsivity symptoms, biotype 1 treated with methylphenidate demonstrated significantly better recovery than biotype 2 treated with atomoxetine (p<0.05, FDR corrected). This imaging-driven, biotype-guided approach holds promise for facilitating personalized treatment of ADHD, exploring possible boundaries through innovative deep learning algorithms aimed at improving medication treatment effectiveness.

Wen, X., Qu, D., Zhang, X. et al. The transition trajectories of self-injurious thoughts and behaviours among children from a biopsychosocial perspective. Nat. Mental Health (2023). https://doi.org/10.1038/s44220-023-00130-z

Although self-injurious thoughts and behaviours (SITB) among children pose an imminent public health concern, the comprehensive understanding of SITB transitions remains unclear. Here we used the longitudinal data of 7,270 children from the Adolescent Brain and Cognitive DevelopmentSM Study (ABCD Study). We found that SITB transitions are linked to altered cortical areas of the dorsal lateral prefrontal cortex and the posterior cingulate cortex and altered functional connectivity between the default mode and attention networks. Additionally, high behaviour inhibition and general psychopathology (that is, p-factor) were identified as risk factors for SITB transitions, while the presence of robust family support and school support served as protective factors. Our study extends prior cross-sectional investigations by elucidating the temporal precedence of specific biopsychosocial factors, underscoring their potential predictive significance in SITB occurrence. Early identification of these factors holds great promise for targeted prevention, addressing the pressing public health concerns associated with SITB.

Rea-Sandin G, Del Toro J, Wilson S. The Heritability of Psychopathology Symptoms in Early Adolescence: Moderation by Family Cultural Values in the ABCD Study. Behav Genet. 2023 Sep 13. doi: 10.1007/s10519-023-10154-x. Epub ahead of print. PMID: 37702839.

Family cultural values that emphasize support, loyalty, and obligation to the family are associated with lower psychopathology in Hispanic/Latino/a youth, but there is a need to understand the implications of family cultural values for youth development in racially/ethnically heterogeneous samples. This study examined phenotypic associations between parent- and youth-reported family cultural values in late childhood on youth internalizing and externalizing symptoms in early adolescence, and whether family cultural values moderated genetic and environmental influences on psychopathology symptoms. The sample comprised 10,335 children (Mage=12.89 years; 47.9% female; 20.3% Hispanic/Latino/a, 15.0% Black, 2.1% Asian, 10.5% other) and their parents from the Adolescent Brain Cognitive Development (ABCD) Study, and biometric models were conducted in the twin subsample (n = 1,042 twin pairs; 43.3% monozygotic). Parents and youth reported on their family cultural values using the Mexican American Cultural Values Scale at youth age 11-12, and parents reported on youth internalizing and externalizing symptoms using the Child Behavior Checklist at youth ages 11-12 and 12-13. Greater parent- and youth-reported family cultural values predicted fewer youth internalizing and externalizing symptoms. Biometric models indicated that higher parent-reported family cultural values increased the nonshared environmental influences on externalizing symptoms whereas youth-reported family cultural values decreased the nonshared environmental influences on internalizing symptoms. This study highlights the need for behavior genetic research to consider a diverse range of cultural contexts to better understand the etiology of youth psychopathology.

Orendain N, Ayaz A, Chung PJ, Bookheimer S, & Galván A. Perceptions of neighborhood threat and caregiver support in early adolescence: Sex differences in neural and behavioral correlates in the ABCD study. Child Abuse & Neglect, Available online 11 September 2023, 106446; https://doi.org/10.1016/j.chiabu.2023.106446

Background
Adolescents, particularly racial and ethnic minorities, are at increased risk for neighborhood threat and violence exposure, which impacts behavioral and neural outcomes. Caregiver support is associated with healthy socioemotional adjustment and self-regulatory and coping behaviors; however, it remains unclear whether caregiver support, specifically, consolation, can moderate the behavioral and neural impacts of neighborhood threat.

Objective
The aim of this study was to examine the role of youth-perceived neighborhood threat on neural and behavioral correlates and to test the moderating potential of caregiver support. Sex differences in associations were examined.

Participants and setting
11,559 nine- and ten-year old youth enrolled in the multi-site Adolescent Brain Cognitive Development (ABCD) Study at baseline.

Methods
Associations were examined via linear regression models employing youth-perceived neighborhood threat and caregiver support. Regression and interaction models controlled for youth age, sex, race and ethnicity, primary caregiver’s education, family income, family structure, youth-perceived school threat, and intracranial volume when examining neural outcomes. An ANOVA employing a Chi-square test and simple slopes analysis were used to identify significant interactions in moderation models.

Results
Neighborhood threat is associated with structural alterations in the left amygdala (p = .004). Meanwhile, caregiver support interacts in a dose-response fashion with neighborhood threat to attenuate its relationship with left amygdala volume (p = .008). Among youth reporting neighborhood threat, problematic behaviors were more common (p < .0001). While not significant, males reported higher rates of neighborhood threat than females (p = .267). Females reported greater levels of caregiver support (p = .017). Lastly, racial and ethnic differences in neighborhood threat and caregiver support were evident (p < .001).

Conclusions
While youth may not have been exposed to direct or immediate sources of threat and violence, these findings shed light on the impact of neighborhood threat perception on problematic behaviors and amygdala volume among nine- and ten-year olds. Future research should identify other culturally inclusive sources and measures of support and resiliency.

Cheng CM, Chu J, Ganson KT, Trompeter N, Testa A, Jackson DB, He J, Glidden DV, Baker FC, Nagata JM. Cyberbullying and eating disorder symptoms in US early adolescents. Int J Eat Disord. 2023 Sep 6. doi: 10.1002/eat.24034. Epub ahead of print. PMID: 37671456.

Objective: The objective of this study was to determine the association between cyberbullying and eating disorder symptoms in a national sample of 10-14-year-old early adolescents.

Method: We analyzed cross-sectional data from the Adolescent Brain Cognitive Development (ABCD) Study (Year 2, 2018-2020, N = 10,258/11,875, 49% female, 46% non-White). Data were collected using multi-stage probability sampling. Modified Poisson regression analyses examined the association between cyberbullying and self-reported eating disorder symptoms based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5).

Results: Cyberbullying victimization was associated with worry about weight gain (prevalence ratio [PR] 2.41, 95% confidence interval [CI] 1.48-3.91), self-worth tied to weight (PR 2.08, 95% CI 1.33-3.26), inappropriate compensatory behavior to prevent weight gain (PR 1.95, 95% CI 1.57-2.42), binge eating (PR 1.95, 95% CI 1.59-2.39), and distress with binge eating (PR 2.64, 95% CI 1.94-3.59), in models adjusting for potential confounders. Cyberbullying perpetration was associated with worry about weight gain (PR 3.52, 95% CI 1.19-10.37), self-worth tied to weight (PR 5.59, 95% CI 2.56-12.20), binge eating (PR 2.36, 95% CI 1.44-3.87), and distress with binge eating (PR 2.84, 95% CI 1.47-5.49).

Discussion: Cyberbullying victimization and perpetration in early adolescence are associated with eating disorder symptoms. Clinicians may consider assessing for cyberbullying and eating disorder symptoms in early adolescence and provide anticipatory guidance.

Public significance statement: Eating disorders often onset in adolescence and have among the highest mortality rates of any psychiatric disorder. In addition, cyberbullying has increased in prevalence among adolescents and significantly impacts mental health. In a national study of early adolescents, we found that cyberbullying victimization and perpetration are associated with eating disorder symptoms. Screening for and providing anticipatory guidance on cyberbullying and eating disorder symptoms in early adolescents may be warranted.

Niu L, Sheffield P, Li Y. Pubertal timing, neighborhood income, and mental health in boys and girls: Findings from the adolescent brain cognitive development study. Social Science & Medicine, Available online 4 September 2023, 116220. https://doi.org/10.1016/j.socscimed.2023.116220

Early pubertal timing is associated with youth mental health problems, with association amplified or mitigated by characteristics of the residential neighborhood. Yet, limited research simultaneously examines the roles of neighborhood context and biological sex in this association. This study fills this research gap by examining sex-specific associations between pubertal timing and neighborhood income with youth mental health problems (internalizing and externalizing symptoms) in a longitudinal cohort of early adolescents in the United States (US). Participants were 9201 youth aged 9 or 10 years from the Adolescent Brain Cognitive Development Study. Pubertal timing was the average of parent- and youth-reported pubertal status standardized within sex and age. Outcomes variables were youths’ internalizing and externalizing symptoms assessed at 1-year follow-up via parent survey. We evaluated interaction effects between pubertal timing and neighborhood income in a series of sex-stratified linear mixed effect models, adjusted for family and personal sociodemographic characteristics. In girls, earlier pubertal timing was associated with more internalizing (β = 0.06, p < 0.001) and externalizing problems (β = 0.07, p < 0.001) at 1-year follow-up, not moderated by neighborhood income. In boys, earlier pubertal timing was associated with more externalizing problems among youth living in high-income neighborhoods, but not among those in low-income neighborhoods (interaction-p = 0.006). Results suggest that pubertal timing may affect youth mental health differentially in boys and girls, depending on the neighborhood contexts. These findings highlight the importance of both biological and social forces in shaping adolescent mental health and, thus, have public health and clinical implications for health promotion.

Vijayakumar N, Youssef G, Bereznicki H, Dehestani N, Silk TJ, Whittle S. The Social Determinants of Emotional and Behavioral Problems in Adolescents Experiencing Early Puberty. J Adolesc Health. 2023 Sep 4:S1054-139X(23)00335-X. doi: 10.1016/j.jadohealth.2023.06.025. Epub ahead of print. PMID: 37665306.

Purpose: Earlier pubertal timing is an important predictor of emotional and behavioral problems during adolescence. The current study undertook a comprehensive investigation of whether the social environment can buffer or amplify the associations between pubertal timing and emotional and behavioral problems.

Methods: Research questions were examined in the Adolescent Brain Cognitive Development (ABCD) Study, a large population representative sample in the United States. We examined interactions between pubertal timing and the shared effects of a range of proximal and distal social environmental influences (i.e., parents, peers, schools, neighborhoods, socioeconomic status) in 10- to 13-year-olds.

Results: Results revealed significant interaction between timing and proximal social influences (i.e., the “microsystem”) in predicting emotional and behavioral problems. In general, adolescents with earlier pubertal timing and unfavorable (high levels of negative and low levels of positive) influences in the microsystem exhibited greater problems. Both males and females exhibited such associations for rule-breaking problems, while females alone exhibited associations for depressive problems. Results also illustrate the relative strength of each social context at moderating risk for emotional and behavioral problems in earlier versus later pubertal maturers.

Discussion: These findings highlight the importance of proximal social influences in buffering vulnerability for emotional and behavioral problems related to earlier puberty. Findings also illustrate the broad implications of latent environmental factors, reflecting common variance of multiple social influences that typically covary with one another.

Harris JC, Liuzzi MT, Cardenas-Iniguez C, et al. Gray space and default mode network-amygdala connectivity. Front. Hum. Neurosci., 30 August 2023, , Sec. Brain Health and Clinical Neuroscience. Volume 17 – 2023 | https://doi.org/10.3389/fnhum.2023.1167786

Introduction: Aspects of the built environment relate to health factors and equity in living conditions, and may contribute to racial, ethnic, or economic health disparities. For example, urbanicity is linked with negative factors including exposure to gray space (e.g., impervious surfaces such as concrete, streets, or rooftops). While there is existing research on access to green space and urbanicity on some mental health and cognitive outcomes, there is limited research on the presence of gray space linked with cognitive functioning in youth. The goal of this study was to investigate the link between gray space and amygdala-default mode network (DMN) connectivity.

Methods: This study used data from the ABCD Study. Participants (n = 10,144; age M = 119.11 months, female = 47.62%) underwent resting-state fMRI acquisition at baseline. Impervious surfaces (gray space) were measured via the Child Opportunity Index (COI). To examine the relationship between presence of gray space and -amygdala-DMN (left/right) connectivity, we employed linear mixed effects models. Correlations were run between amygdala-DMN connectivity and internalizing and externalizing symptoms. Finally, post hoc sensitivity analyses were run to assess the impact of race.

Results: More gray space, adjusting for age, sex, and neighborhood-level variables, was significantly associated with increased left amygdala-DMN connectivity (p = 0.0001). This association remained significant after sensitivity analyses for race were completed (p = 0.01). No significant correlations were observed between amygdala-DMN and internalizing or externalizing symptoms.

Discussion: Findings suggest gray space was linked with increased left amygdala-DMN connectivity, circuits that have been implicated in affective processing, emotion regulation, and psychopathology. Thus gray space may be related to alterations in connectivity that may enhance risk for emotion dysregulation. Future investigation of these relationships is needed, as neuroimaging findings may represent early dysregulation not yet observed in the behavioral analyses at this age (i.e., the present study did not find significant relationships with parent-reported behavioral outcomes). These findings can help to inform future public policy on improving lived and built environments.

Zhang L, Cui Z, Huffman LG, Oshri A. Sleep mediates the effect of stressful environments on youth development of impulsivity: The moderating role of within default mode network resting-state functional connectivity. Sleep Health. 2023 Aug;9(4):503-511. doi: 10.1016/j.sleh.2023.03.005. Epub 2023 Jun 1. PMID: 37270396.

Objectives: Youth raised in stressful environments are at increased risk for developing impulsive traits, which are a robust precursor of problem behaviors. Sleep may mediate the link between stress and problem behaviors as it is both sensitive to stress and essential for neurocognitive development underlying behavioral control during adolescence. The default mode network (DMN) is a brain network implicated in stress regulation and sleep. Yet, it is poorly understood how individual differences in resting-state DMN moderate the effect of stressful environments on impulsivity via sleep problems.

Methods: Three waves of data spanning 2 years were obtained from the Adolescent Brain and Cognitive Development Study, a national longitudinal sample of 11,878 children (Mage at baseline = 10.1; 47.8% female). Structural equation modeling was used to test (a) the mediating role of sleep at T3 in the link between stressful environments at baseline and impulsivity at T5 and (b) the moderation of this indirect association by baseline levels of within-DMN resting-state functional connectivity.

Results: Sleep problems, shorter sleep duration, and longer sleep latency significantly mediated the link between stressful environments and youth impulsivity. Youth with elevated within-DMN resting-state functional connectivity showed intensified associations between stressful environments and impulsivity via shorter sleep duration.

Conclusion: Our findings suggest that sleep health can be a target for preventive intervention and thereby mitigate the link between stressful environments and increased levels of youth impulsivity.

Mewton L, Davies S, Sunderland M, Champion K, Hoy N, Newton N, Teesson M, Squeglia LM. Longitudinal relationships between lifestyle risk factors and neurodevelopment in early adolescence. Health Psychol. 2023 Aug 24. doi: 10.1037/hea0001248. Epub ahead of print. PMID: 37616102.

Objective: The goal of this study is to investigate the cross-sectional and longitudinal relationships between clustered lifestyle risk factors (sleep, physical activity, body mass index [BMI], and screen time) and neurodevelopment over the early adolescent period.

Method: Data from the ABCD Study Data Release 3.0 consisted of 11,878 participants (aged 9-10 years) at baseline and 6,571 participants (aged 11-12 years) at 2-year follow-up. The interrelationships between lifestyle risk factors and brain structure were analyzed using bivariate multiple indicator latent change score models. Using confirmatory factor analysis, a single lifestyle risk factor domain (measured by sleep, physical activity, BMI, and screen time) was shown to fit the data well. Using exploratory and confirmatory factor analysis, seven brain structure domains were extracted and labeled as temporal-parietal, frontotemporal, occipital, orbitofrontal, temporal, cingulate, parietal, and cuneus domains. All bivariate latent change score models accounted for age, sex at birth, race/ethnicity, parental education, and marital status.

Results: Higher lifestyle risk was associated with smaller brain volume at baseline. Higher baseline lifestyle risk was also associated with a greater rate of change (i.e., greater decreases) in brain volume for the temporal-parietal, frontotemporal, orbitofrontal, parietal, and cuneus domains. Effects were not reciprocal; baseline brain volume did not predict changes in lifestyle behaviors over time.

Conclusion: These findings are important for understanding the biological mechanisms underpinning health risk factors and can be used to target interventions and improve brain health during this critical developmental phase.

Xia J, Chen N, Qiu A. Multi-level and joint attention networks on brain functional connectivity for cross-cognitive prediction. Med Image Anal. 2023 Aug 21;90:102921. doi: 10.1016/j.media.2023.102921. Epub ahead of print. PMID: 37666116.

Deep learning on resting-state functional MRI (rs-fMRI) has shown great success in predicting a single cognition or mental disease. Nevertheless, cognitive functions or mental diseases may share neural mechanisms that can benefit their prediction/classification. We propose a multi-level and joint attention (ML-Joint-Att) network to learn high-order representations of brain functional connectivities that are specific and shared across multiple tasks. We design the ML-Joint-Att network with edge and node convolutional operators, an adaptive inception module, and three attention modules, including network-wise, region-wise, and region-wise joint attention modules. The adaptive inception learns brain functional connectivity at multiple spatial scales. The network-wise and region-wise attention modules take the multi-scale functional connectivities as input and learn features at the network and regional levels for individual tasks. Moreover, the joint attention module is designed as region-wise joint attention to learn shared brain features that contribute to and compensate for the prediction of multiple tasks. We employed the Adolescent Brain Cognitive Development (ABCD) dataset (n =9092) to evaluate the ML-Joint-Att network for the prediction of cognitive flexibility and inhibition. Our experiments demonstrated the usefulness of the three attention modules and identified brain functional connectivities and regions specific and common between cognitive flexibility and inhibition. In particular, the joint attention module can significantly improve the prediction of both cognitive functions. Moreover, leave-one-site cross-validation showed that the ML-Joint-Att network is robust to independent samples obtained from different sites of the ABCD study. Our network outperformed existing machine learning techniques, including Brain Bias Set (BBS), spatio-temporal graph convolution network (ST-GCN), and BrainNetCNN. We demonstrated the generalization of our method to other applications, such as the prediction of fluid intelligence and crystallized intelligence, which also outperformed the ST-GCN and BrainNetCNN.

Zhang R, Murray SB, Duval CJ, Wang DJJ, Jann K. Functional Connectivity and Complexity Analyses of Resting-State fMRI in Pre-Adolescents with ADHD. medRxiv [Preprint]. 2023 Aug 21:2023.08.17.23294136. doi: 10.1101/2023.08.17.23294136. PMID: 37662367; PMCID: PMC10473793.

Attention deficit hyperactivity disorder (ADHD) has been characterized by impairments among distributed functional brain networks, e.g., the frontoparietal network (FPN), default mode network (DMN), and reward and motivation-related circuits (RMN). In the current study, we evaluated the complexity and functional connectivity (FC) of resting state fMRI (rsfMRI) in pre-adolescents with ADHD for pathology-relevant networks. We leveraged data from the Adolescent Brain and Cognitive Development (ABCD) Study. The final study sample included 63 children with ADHD and 92 healthy control children matched on age, sex, and pubertal development status. For selected regions in relevant networks, ANCOVA compared multiscale entropy (MSE) and FC between the groups. Finally, differences in the association between MSE and FC were evaluated. We found significantly reduced MSE along with increased FC within the FPN of pre-adolescents with ADHD compared to matched healthy controls. Significant partial correlations between MSE and FC emerged in fewer regions in the participants with ADHD than in the controls. The observation of reduced entropy is consistent with existing literature using rsfMRI and other neuroimaging modalities. The current findings of complexity and FC in ADHD support hypotheses of altered function of inhibitory control networks in ADHD.

Ray B, Chen J, Fu Z, Suresh P, Thapaliya B, Farahdel B, Calhoun VD, Liu J. Replication and Refinement of Brain Age Model for adolescent development. bioRxiv [Preprint]. 2023 Aug 18:2023.08.16.553472. doi: 10.1101/2023.08.16.553472. PMID: 37645839; PMCID: PMC10462059.

The discrepancy between chronological age and estimated brain age, known as the brain age gap, may serve as a biomarker to reveal brain development and neuropsychiatric problems. This has motivated many studies focusing on the accurate estimation of brain age using different features and models, of which the generalizability is yet to be tested. Our recent study has demonstrated that conventional machine learning models can achieve high accuracy on brain age prediction during development using only a small set of selected features from multimodal brain imaging data. In the current study, we tested the replicability of various brain age models on the Adolescent Brain Cognitive Development (ABCD) cohort. We proposed a new refined model to improve the robustness of brain age prediction. The direct replication test for existing brain age models derived from the age range of 8-22 years onto the ABCD participants at baseline (9 to 10 years old) and year-two follow-up (11 to 12 years old) indicate that pre-trained models could capture the overall mean age failed precisely estimating brain age variation within a narrow range. The refined model, which combined broad prediction of the pre-trained model and granular information with the narrow age range, achieved the best performance with a mean absolute error of 0.49 and 0.48 years on the baseline and year-two data, respectively. The brain age gap yielded by the refined model showed significant associations with the participants’ information processing speed and verbal comprehension ability on baseline data.

Lombardo D, Kaufmann T. Different patterns of intrinsic functional connectivity at the default mode and attentional networks predict crystalized and fluid abilities in childhood. Cereb Cortex Commun. 2023 Aug 17;4(3):tgad015. doi: 10.1093/texcom/tgad015. PMID: 37675438; PMCID: PMC10477707.

Crystallized abilities are skills used to solve problems based on experience, while fluid abilities are linked to reasoning without evoke prior knowledge. To what extent crystallized and fluid abilities involve dissociated or overlapping neural systems is debatable. Due to often deployed small sample sizes or different study settings in prior work, the neural basis of crystallized and fluid abilities in childhood remains largely unknown. Here we analyzed within and between network connectivity patterns from resting-state functional MRI of 2707 children between 9 and 10 years from the ABCD study. We hypothesized that differences in functional connectivity at the default mode network (DMN), ventral, and dorsal attentional networks (VAN, DAN) explain differences in fluid and crystallized abilities. We found that stronger between-network connectivity of the DMN and VAN, DMN and DAN, and VAN and DAN predicted crystallized abilities. Within-network connectivity of the DAN predicted both crystallized and fluid abilities. Our findings reveal that crystallized abilities rely on the functional coupling between attentional networks and the DMN, whereas fluid abilities are associated with a focal connectivity configuration at the DAN. Our study provides new evidence into the neural basis of child intelligence and calls for future comparative research in adulthood during neuropsychiatric diseases.

Raney JH, Al-Shoaibi AA, Shao IY, Ganson KT, Testa A, Jackson DB, He J, Glidden DV, Nagata JM. Racial discrimination is associated with binge-eating disorder in early adolescents: a cross-sectional analysis. J Eat Disord. 2023 Aug 17;11(1):139. doi: 10.1186/s40337-023-00866-0. PMID: 37592364.

Background: Racial and ethnic discrimination are known stressors and are associated with negative psychological and physical health outcomes. Previous studies have found relationships between racial/ethnic discrimination and binge-eating disorder (BED), though they have mainly focused on adult populations. The aim of this study was to determine associations between racial/ethnic discrimination and BED in a large, national cohort study of early adolescents. We further sought to explore associations between the racial/ethnic discrimination perpetrator (students, teachers, or other adults) and BED.

Methods: We analyzed cross-sectional data from the Adolescent Brain Cognitive Development Study (N = 11,075, 2018-2020). Logistic regression analyses examined associations between self-reported experiences of racial or ethnic discrimination and binge-eating behaviors and diagnosis, adjusting for potential confounders. Racial/ethnic discrimination measures were assessed based on the Perceived Discrimination Scale, which measures experiences of discrimination based on race/ethnicity and frequency of ethnic discrimination by teachers, adults outside of school, and students. Binge-eating behaviors and diagnosis were based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSAD-5).

Results: In this racially diverse sample of adolescents (N = 11,075, age range 9-12 years), 4.7% of adolescents reported racial or ethnic discrimination and 1.1% met the criteria for BED. In the adjusted models, racial/ethnic discrimination was associated with 3 times higher odds of having BED (OR 3.31, CI 1.66-7.74). Further, experiences of ethnic discrimination by students and adults outside school were associated with significantly increased odds of BED diagnosis (OR 1.36, CI 1.10-1.68 and OR 1.42 CI 1.06-1.90, respectively)., Increased odds of binge eating behaviors were only significantly associated with ethnic discrimination perpetuated by students (OR 1.12, CI 1.02-1.23).

Conclusions: Children and adolescents who have experienced racial/ethnic discrimination, particularly when discrimination was perpetuated by other students, have higher odds of having binge-eating behaviors and diagnoses. Clinicians may consider screening for racial discrimination and providing anti-racist, trauma-informed care when evaluating and treating patients for BED.

Warrier V, Stauffer EM, Huang QQ, Wigdor EM, Slob EAW, Seidlitz J, Ronan L, Valk SL, Mallard TT, Grotzinger AD, Romero-Garcia R, Baron-Cohen S, Geschwind DH, Lancaster MA, Murray GK, Gandal MJ, Alexander-Bloch A, Won H, Martin HC, Bullmore ET, Bethlehem RAI. Genetic insights into human cortical organization and development through genome-wide analyses of 2,347 neuroimaging phenotypes. Nat Genet. 2023 Aug 17. doi: 10.1038/s41588-023-01475-y. Epub ahead of print. PMID: 37592024.

Our understanding of the genetics of the human cerebral cortex is limited both in terms of the diversity and the anatomical granularity of brain structural phenotypes. Here we conducted a genome-wide association meta-analysis of 13 structural and diffusion magnetic resonance imaging-derived cortical phenotypes, measured globally and at 180 bilaterally averaged regions in 36,663 individuals and identified 4,349 experiment-wide significant loci. These phenotypes include cortical thickness, surface area, gray matter volume, measures of folding, neurite density and water diffusion. We identified four genetic latent structures and causal relationships between surface area and some measures of cortical folding. These latent structures partly relate to different underlying gene expression trajectories during development and are enriched for different cell types. We also identified differential enrichment for neurodevelopmental and constrained genes and demonstrate that common genetic variants associated with cortical expansion are associated with cephalic disorders. Finally, we identified complex interphenotype and inter-regional genetic relationships among the 13 phenotypes, reflecting the developmental differences among them. Together, these analyses identify distinct genetic organizational principles of the cortex and their correlates with neurodevelopment.

Ren J, Loughnan R, Xu B, Thompson WK, Fan CC. Estimating the Total Variance Explained by Whole-Brain Imaging for Zero-inflated Outcomes. bioRxiv [Preprint]. 2023 Aug 16:2023.08.14.553270. doi: 10.1101/2023.08.14.553270. PMID: 37645753; PMCID: PMC10462013.

Zero-inflated outcomes are very common in behavioral data, particularly for responses to psychological questionnaires. Modeling these challenging distributions is further exacerbated by the absence of established statistical models capable of characterizing total signals attributed to whole-brain imaging features, making the accurate assessment of brain-behavior relationships particularly formidable. Given this critical need, we have developed a novel variational Bayes algorithm that characterizes the total signal captured by whole-brain imaging features for zero-inflated outcomes . Our zero-inflated variance (ZIV) estimator robustly estimates the fraction of variance explained (FVE) and the proportion of non-null effects from large-scale imaging data. In simulations, ZIV outperformed other linear prediction algorithms. Applying ZIV to data from one of the largest neuroimaging studies, the Adolescent Brain Cognitive Development SM (ABCD) Study, we found that whole-brain imaging features have a larger FVE for externalizing compared to internalizing behavior. We also demonstrate that the ZIV estimator, especially applied to focal sub-scales, can localize key neurocircuitry associated with human behavior.

Tomasi D, Volkow ND. Effects of family income on brain functional connectivity in US children: associations with cognition. Mol Psychiatry. 2023 Aug 14. doi: 10.1038/s41380-023-02222-9. Epub ahead of print. PMID: 37580525.

Saadi A, Choi KR, Khan T, Tang JT, Iverson GL. Examining the Association Between Adverse Childhood Experiences and Lifetime History of Head or Neck Injury and Concussion in Children From the United States. J Head Trauma Rehabil. 2023 Aug 14. doi: 10.1097/HTR.0000000000000883. Epub ahead of print. PMID: 37582185.

Objective: Our objective was to determine whether there is an association between adverse childhood experiences (ACEs) and lifetime history of early childhood mild head or neck injury and concussion in a nationally representative US cohort.

Setting and design: This is a cross-sectional study using data from the Adolescent Brain Cognitive Development (ABCD) Study (data release 3.0), a prospective investigation of child brain development and health.

Participants: There were 11 878 children aged 9 or 10 years at baseline, recruited from 21 school-based sites in the United States. After excluding children with missing questionnaires for the primary exposure variable and children with severe brain injuries involving more than 30-minute loss of consciousness, the final sample size was 11 230 children.

Measures: The primary exposure variable was ACEs. We measured eight ACEs: sexual abuse, physical abuse, emotional neglect, parent domestic violence, parent substance use disorder, parental mental illness, parent criminal involvement, and parent divorce. The primary outcomes were head or neck injury and concussion, measured using the Ohio State University Traumatic Brain Injury Screen-Identification Method Short Form.

Results: The sample (N = 11 230) was 52% boys with a mean age of 9.9 years (SD = 0.62 years). The racial and ethnic makeup was reflective of national demographics. Having a higher overall ACE count was associated with higher odds of head or neck injury, with greater odds with more ACEs reported. Children with 2 ACEs had 24% greater odds of head or neck injury (AOR = 1.24, 95% confidence interval [CI] = 1.06-1.45) and 64% greater odds of concussion (AOR = 1.64, 95% CI = 1.18-2.22), and children with 4 or more ACEs had 70% greater odds of head or neck injury (AOR = 1.7, 95% CI = 1.14, 2.49) and 140% greater odds of concussion (AOR = 2.4, 95% CI = 1.15-4.47). The individual ACE categories of sexual abuse, parent domestic violence, parental mental illness, and parent criminal involvement were significantly associated with increased risk of head or neck injury and parental mental illness with increased risk of concussion.

Conclusions and relevance: ACEs are associated with early childhood mild head or neck injury and concussion and should be integrated in head injury prevention and intervention efforts.

Betts SS, Adise S, Rezvan PH, et al. Socioeconomic Adversity and Weight Gain During the COVID-19 Pandemic. JAMA Pediatr. Published online August 14, 2023. doi:10.1001/jamapediatrics.2023.2823

Rates of pediatric obesity reached unprecedented levels during the COVID-19 pandemic,¹ when children and adolescents experienced sudden changes to their routines, increased stress, and decreased opportunity for exercise and proper nutrition.² Pandemic burdens were greater for low-income populations,³ who are disproportionately affected by obesity.⁴ We capitalized on the natural experiment of COVID-19 in the Adolescent Brain Cognitive Development (ABCD) Study, by comparing weight gain of participants (1- and 2-year follow-up assessments acquired before March 2020) with weight gain of participants whose 2-year follow-up occurred after the COVID-19 lockdown. This allowed us to investigate the impact of the pandemic longitudinally, as associated with socioeconomic disadvantage, in a large, demographically diverse sample of US youth.

Saadi A, Choi KR, Khan T, Tang JT, Iverson GL. Examining the Association Between Adverse Childhood Experiences and Lifetime History of Head or Neck Injury and Concussion in Children From the United States. J Head Trauma Rehabil. 2023 Aug 14. doi: 10.1097/HTR.0000000000000883. Epub ahead of print. PMID: 37582185.

Objective: Our objective was to determine whether there is an association between adverse childhood experiences (ACEs) and lifetime history of early childhood mild head or neck injury and concussion in a nationally representative US cohort.

Setting and design: This is a cross-sectional study using data from the Adolescent Brain Cognitive Development (ABCD) Study (data release 3.0), a prospective investigation of child brain development and health.

Participants: There were 11 878 children aged 9 or 10 years at baseline, recruited from 21 school-based sites in the United States. After excluding children with missing questionnaires for the primary exposure variable and children with severe brain injuries involving more than 30-minute loss of consciousness, the final sample size was 11 230 children.

Measures: The primary exposure variable was ACEs. We measured eight ACEs: sexual abuse, physical abuse, emotional neglect, parent domestic violence, parent substance use disorder, parental mental illness, parent criminal involvement, and parent divorce. The primary outcomes were head or neck injury and concussion, measured using the Ohio State University Traumatic Brain Injury Screen-Identification Method Short Form.

Results: The sample (N = 11 230) was 52% boys with a mean age of 9.9 years (SD = 0.62 years). The racial and ethnic makeup was reflective of national demographics. Having a higher overall ACE count was associated with higher odds of head or neck injury, with greater odds with more ACEs reported. Children with 2 ACEs had 24% greater odds of head or neck injury (AOR = 1.24, 95% confidence interval [CI] = 1.06-1.45) and 64% greater odds of concussion (AOR = 1.64, 95% CI = 1.18-2.22), and children with 4 or more ACEs had 70% greater odds of head or neck injury (AOR = 1.7, 95% CI = 1.14, 2.49) and 140% greater odds of concussion (AOR = 2.4, 95% CI = 1.15-4.47). The individual ACE categories of sexual abuse, parent domestic violence, parental mental illness, and parent criminal involvement were significantly associated with increased risk of head or neck injury and parental mental illness with increased risk of concussion.

Conclusions and relevance: ACEs are associated with early childhood mild head or neck injury and concussion and should be integrated in head injury prevention and intervention efforts.

Feinstein BA, van der Star A, Dorrell KD, Blashill AJ. Sexual orientation and mental health in a US cohort of children: a longitudinal mediation study. J Child Psychol Psychiatry. 2023 Aug 10. doi: 10.1111/jcpp.13873. Epub ahead of print. PMID: 37565595.

Background: Sexual minorities, including children, are at increased risk for adverse mental health outcomes compared to their heterosexual peers, but longitudinal studies are needed to determine the factors that explain the associations between sexual minority identification and adverse mental health outcomes during this developmental period. We examined longitudinal associations between sexual orientation and mental health over 2 years in a US cohort of children (aged 9-10 at baseline) and two explanatory factors (increased social problems such as getting teased and decreased perceived school safety). We hypothesized that beginning to identify as gay/bisexual and consistently identifying as gay/bisexual would be associated with increases in internalizing (e.g. depression, anxiety) and externalizing (e.g. aggression) problems compared to consistently identifying as heterosexual, and these associations would be partially explained by increased social problems and decreased perceived school safety.

Methods: We used data from Waves 1-3 of the Adolescent Brain Cognitive Development study. The analytic sample included 5,574 children (46.0% female; 55.1% non-Hispanic White).

Results: Beginning to identify as gay/bisexual was associated with increased internalizing/externalizing problems, and consistently identifying as gay/bisexual was associated with increased internalizing problems, compared to consistently identifying as heterosexual. For those who consistently identified as gay/bisexual, increased disparities in internalizing problems were partially explained by increased social problems and decreased perceived school safety, and increased disparities in externalizing problems were partially explained by increased social problems.

Conclusions: These findings suggest the health disparities affecting sexual minority children include both internalizing and externalizing problems, and social problems and feeling unsafe at school may be contributing factors.

Harris JC, Liuzzi MT, Cardenas-Iniguez C, et al. Gray space and default mode network-amygdala connectivity. Front. Hum. Neurosci., Sec. Brain Health and Clinical Neuroscience, Volume 17 – 2023 | doi: 10.3389/fnhum.2023.1167786.

Introduction: Aspects of the built environment relate to health factors and equity in living conditions, and may contribute to racial, ethnic, or economic health disparities. For example, urbanicity is linked with negative factors including exposure to gray space (e.g., impervious surfaces such as concrete, streets, or rooftops). While there is existing research on access to green space and urbanicity on some mental health and cognitive outcomes, there is limited research on the presence of gray space linked with cognitive functioning in youth. The goal of this study was to investigate the link between gray space and amygdala-default mode network (DMN) connectivity. Method: This study used data from the ABCD Study. Participants (n=10,144; age M = 119.11 months, female = 47.62%) underwent resting-state fMRI acquisition at baseline. Impervious surfaces (gray space) were measured via the Child Opportunity Index (COI). To examine the relationship between presence of gray space and -amygdala-DMN (left/right) connectivity, we employed linear mixed effects models. Correlations were run between amygdala-DMN connectivity and internalizing and externalizing symptoms. Finally, post-hoc sensitivity analyses were run to assess the impact of race. Results: More gray space, adjusting for age, sex, and neighborhood-level variables, was significantly associated with increased left amygdala-DMN connectivity (p=0.0001). This association remained significant after sensitivity analyses for race were completed (p=0.01). No significant correlations were observed between amygdala-DMN and internalizing or externalizing symptoms. Discussion: Findings suggest gray space was linked with increased left amygdala-DMN connectivity, circuits that have been implicated in affective processing, emotion regulation, and psychopathology. Thus gray space may be related to alterations in connectivity that may enhance risk for emotion dysregulation. Future investigation of these relationships is needed, as neuroimaging findings may represent early dysregulation not yet observed in the behavioral analyses at this age (i.e., the present study did not find significant relationships with parent reported behavioral outcomes). These findings can help to inform future public policy on improving lived and built environments.

Shao IY, Al-Shoaibi AAA, Trompeter N, Testa A, Ganson KT, Baker FC, Nagata JM. Association of cyberbullying victimization and substance initiation: The Adolescent Brain Cognitive Development (ABCD) study. Drug Alcohol Depend. 2023 Aug 8;251:110920. doi: 10.1016/j.drugalcdep.2023.110920. Epub ahead of print. PMID: 37598455.

Background: Evidence shows that cyberbullying is an important risk factor for various adverse mental health outcomes, such as substance use. However, there is limited evidence from longitudinal studies that assessed whether cyberbullying victimization is associated with substance use initiation, especially among adolescent population.

Methods: Using data from the Adolescent Brain Cognitive Development Study, we assessed the association between cyberbullying victimization and substance use initiation among adolescents. In the cross-sectional analysis at year 2, multivariable logistic regressions were used to assess the association between cyberbullying victimization history and substance use initiation. Additionally, the association between year 2 cyberbullying victimization in the past 12 months/lifetime and year 3 substance use initiation was assessed using multivariable logistic regression.

Results: Adjusting for sociodemographic characteristics and the presence of depression/anxiety symptoms, lifetime history of cyberbullying victimization was significantly associated with substance use initiation (OR= 2.17, 95% CI: 1.68, 2.81). Recent cyberbullying victimization in the past 12 months was associated with two-times higher odds of initiating substances (OR= 2.31, 95% CI: 1.71, 3.12). In addition, both lifetime history of cyberbullying victimization and recent cyberbullying victimization at year 2 were associated with two times increased risk in substance use initiation at year 3 (OR = 2.22, 95% CI: 1.68, 2.93; OR = 2.34, 95% CI: 1.68, 3.26).

Conclusion: There is a significant relationship between cyberbullying victimization and substance use initiation among adolescents. Cyberbullying victims are at an increased risk of initiating substance use later in life.

Gass, N. The beauty of reading for pleasure. Nat. Mental Health 1, 529 (2023). https://doi.org/10.1038/s44220-023-00108-x

In a new study, Yun-Jun Sun, Barbara Sahakian et al. examined the relationship between childhood RfP and brain structure, cognition and mental wellbeing in adolescence. Using a sample of more than 10,000 young adolescents from the Adolescent Brain Cognitive Development (ABCD) cohort, the researchers assessed brain scans, cognitive test scores, academic performance, anxiety, stress, depression scores, and psychopathological behavior, including aggression and rule-breaking. They divided the adolescents into two groups: one with a RfP duration of 3–10 years and the other with 0–2.5 years. “Adolescence is the transition between being a child to becoming an adult and so interventions in childhood that are beneficial for cognition, school academic attainment and mental health are extremely important. Many mental health disorders begin in childhood or adolescence, so improving mental health during these developmental periods is crucial,” explains Sahakian, a joint first author of the paper.

Liu K, Thompson RC, Watson J, Montena AL, Warren SL. Developmental Trajectories of Internalizing and Externalizing Symptoms in Youth and Associated Gender Differences: A Directed Network Perspective. Res Child Adolesc Psychopathol. 2023 Aug 7. doi: 10.1007/s10802-023-01106-4. Epub ahead of print. PMID: 37548898.

Psychopathology in youth is highly prevalent and associated with psychopathology in adulthood. However, the developmental trajectories of psychopathology symptoms, including potential gender differences, are markedly underspecified. The present study employed a directed network approach to investigate longitudinal relationships and gender differences among eight transdiagnostic symptom domains across three years, in a homogenous age sample of youth participants (n = 6,414; mean baseline age = 10.0 years; 78.6% White; Adolescent Brain Cognitive Development study). Anxious/depressed problems and aggressive behaviors were central symptoms and most predictive of increases in other symptom clusters at later timepoints. Rule-breaking behaviors, aggressive behaviors, and withdrawn/depressed problems emerged as bridge symptoms between externalizing and internalizing problems. Results supported cascade models in which externalizing problems predicted future internalizing problems, but internalizing problems also significantly predicted future externalizing problems, which is contrary to cascade models. Network structure, symptom centrality, and patterns of bridge symptoms differed between female and male participants, suggesting gender differences in the developmental trajectories of youth psychopathology. Results provide new insights into symptom trajectories and associated gender differences that may provide promising pathways for understanding disorder (dis)continuity and co-occurrence. The central and bridge symptoms identified here may have important implications for screening and early intervention for youth psychopathology.

Kuang, N., Liu, Z., Yu, G. et al. Neurodevelopmental risk and adaptation as a model for comorbidity among internalizing and externalizing disorders: genomics and cell-specific expression enriched morphometric study. BMC Med 21, 291 (2023). https://doi.org/10.1186/s12916-023-02920-9

Background
Comorbidity is the rule rather than the exception for childhood and adolescent onset mental disorders, but we cannot predict its occurrence and do not know the neural mechanisms underlying comorbidity. We investigate if the effects of comorbid internalizing and externalizing disorders on anatomical differences represent a simple aggregate of the effects on each disorder and if these comorbidity-associated cortical surface differences relate to a distinct genetic underpinning.

Methods
We studied the cortical surface area (SA) and thickness (CT) of 11,878 preadolescents (9–10 years) from the Adolescent Brain and Cognitive Development Study. Linear mixed models were implemented in comparative and association analyses among internalizing (dysthymia, major depressive disorder, disruptive mood dysregulation disorder, agoraphobia, panic disorder, specific phobia, separation anxiety disorder, social anxiety disorder, generalized anxiety disorder, post-traumatic stress disorder), externalizing (attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder) diagnostic groups, a group with comorbidity of the two and a healthy control group. Genome-wide association analysis (GWAS) and cell type specificity analysis were performed on 4468 unrelated European participants from this cohort.

Results
Smaller cortical surface area but higher thickness was noted across patient groups when compared to controls. Children with comorbid internalizing and externalizing disorders had more pronounced areal reduction than those without comorbidity, indicating an additive burden. In contrast, cortical thickness had a non-linear effect with comorbidity: the comorbid group had no significant CT differences, while those patient groups without comorbidity had significantly higher thickness compare to healthy controls. Distinct biological pathways were implicated in regional SA and CT differences. Specifically, CT differences were associated with immune-related processes implicating astrocytes and oligodendrocytes, while SA-related differences related mainly to inhibitory neurons.

Conclusion
The emergence of comorbidity across distinct clusters of psychopathology is unlikely to be due to a simple additive neurobiological effect alone. Distinct developmental risk moderated by immune-related adaptation processes, with unique genetic and cell-specific factors, may contribute to underlying SA and CT differences. Children with the highest risk but lowest resilience, both captured in their developmental morphometry, may develop a comorbid illness pattern.

Rozzell-Voss KN, Klimek-Johnson P, Eichen DM, et al. Executive function differences as a function of parent-reported binge eating and weight: Results from the adolescent brain cognitive development study. Obesity Science and Practice. 03 August 2023, https://doi.org/10.1002/osp4.703.

Background
Binge eating is a relatively common disordered eating behavior among children, and is associated with poor health outcomes. Executive function (EF)—higher order cognitive abilities related to planning and impulse control—may be implicated in both binge eating and pediatric obesity. Although EF deficits are evident among individuals with obesity and/or binge eating, findings are mixed across the lifespan.

Methods
The present study examined differences in EF among children with varying weight statuses and parent-reported binge eating. The sample included 10,017 children from the Adolescent Brain Cognitive Development study, aged 9–10 years.

Results
Children with parent-reported binge eating—either with overweight/obesity or normal weight—had significantly lower EF than those with no binge eating and a normal weight status but did not differ from those with no binge eating and overweight/obesity. Children with no binge eating and overweight/obesity also had statistically significantly lower EF than those with normal weight status. Although all significant differences between groups were negligible to very small, results may indicate similar neurocognitive profiles among children with binge eating and those with overweight/obesity.

Conclusions
Alterations in EF among children with binge eating may not be solely related to weight-specific factors, as significant differences also emerged among children with normal weight status, with versus without parent-reported binge eating. Future research is needed to understand temporal associations between obesity, disordered eating, and neurocognition in children using multi-informant methods for assessing binge eating.

Passiatore R, Antonucci LA, DeRamus TP, Fazio L, Stolfa G, Sportelli L, Kikidis GC, Blasi G, Chen Q, Dukart J, Goldman AL, Mattay VS, Popolizio T, Rampino A, Sambataro F, Selvaggi P, Ulrich W; Apulian Network on Risk for Psychosis; Weinberger DR, Bertolino A, Calhoun VD, Pergola G. Changes in patterns of age-related network connectivity are associated with risk for schizophrenia. Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2221533120. doi: 10.1073/pnas.2221533120. Epub 2023 Aug 1. PMID: 37527347.

Alterations in fMRI-based brain functional network connectivity (FNC) are associated with schizophrenia (SCZ) and the genetic risk or subthreshold clinical symptoms preceding the onset of SCZ, which often occurs in early adulthood. Thus, age-sensitive FNC changes may be relevant to SCZ risk-related FNC. We used independent component analysis to estimate FNC from childhood to adulthood in 9,236 individuals. To capture individual brain features more accurately than single-session fMRI, we studied an average of three fMRI scans per individual. To identify potential familial risk-related FNC changes, we compared age-related FNC in first-degree relatives of SCZ patients mostly including unaffected siblings (SIB) with neurotypical controls (NC) at the same age stage. Then, we examined how polygenic risk scores for SCZ influenced risk-related FNC patterns. Finally, we investigated the same risk-related FNC patterns in adult SCZ patients (oSCZ) and young individuals with subclinical psychotic symptoms (PSY). Age-sensitive risk-related FNC patterns emerge during adolescence and early adulthood, but not before. Young SIB always followed older NC patterns, with decreased FNC in a cerebellar-occipitoparietal circuit and increased FNC in two prefrontal-sensorimotor circuits when compared to young NC. Two of these FNC alterations were also found in oSCZ, with one exhibiting reversed pattern. All were linked to polygenic risk for SCZ in unrelated individuals (R² varied from 0.02 to 0.05). Young PSY showed FNC alterations in the same direction as SIB when compared to NC. These results suggest that age-related neurotypical FNC correlates with genetic risk for SCZ and is detectable with MRI in young participants.

Yang B, Anderson Z, Zhou Z, Liu S, Haase CM, Qu Y. The longitudinal role of family conflict and neural reward sensitivity in youth’s internalizing symptoms. Soc Cogn Affect Neurosci. 2023 Aug 2;18(1):nsad037. doi: 10.1093/scan/nsad037. PMID: 37531585.

Adolescence is often associated with an increase in psychopathology. Although previous studies have examined how family environments and neural reward sensitivity separately play a role in youth’s emotional development, it remains unknown how they interact with each other in predicting youth’s internalizing symptoms. Therefore, the current research took a biopsychosocial approach to examine this question using two-wave longitudinal data of 9353 preadolescents (mean age = 9.93 years at T1; 51% boys) from the Adolescent Brain Cognitive Development study. Using mixed-effects models, results showed that higher family conflict predicted youth’s increased internalizing symptoms 1 year later, whereas greater ventral striatum (VS) activity during reward receipt predicted reduced internalizing symptoms over time. Importantly, there was an interaction effect between family conflict and VS activity. For youth who showed greater VS activation during reward receipt, high family conflict was more likely to predict increased internalizing symptoms. In contrast, youth with low VS activation during reward receipt showed high levels of internalizing symptoms regardless of family conflict. The findings suggest that youth’s neural reward sensitivity is a marker of susceptibility to adverse family environments and highlight the importance of cultivating supportive family environments where youth experience less general conflict within the family.

Bottenhorn KL, Cardenas-Iniguez C, Mills KL, Laird AR, Herting MM. Profiling intra- and inter-individual differences in brain development across early adolescence. Neuroimage. 2023 Aug 1:120287. doi: 10.1016/j.neuroimage.2023.120287. Epub ahead of print. PMID: 37536527.

As we move toward population-level developmental neuroscience, understanding intra- and inter-individual variability in brain maturation and sources of neurodevelopmental heterogeneity becomes paramount. Large-scale, longitudinal neuroimaging studies have uncovered group-level neurodevelopmental trajectories, and while recent work has begun to untangle intra- and inter-individual differences, they remain largely unclear. Here, we aim to quantify both intra- and inter-individual variability across facets of neurodevelopment across early adolescence (ages 8.92 to 13.83 years) in the Adolescent Brain Cognitive Development (ABCD) Study and examine inter-individual variability as a function of age, sex, and puberty. Our results provide novel insight into differences in annualized percent change in macrostructure, microstructure, and functional brain development from ages 9-13 years old. These findings reveal moderate age-related intra-individual change, but age-related differences in inter-individual variability only in a few measures of cortical macro- and microstructure development. Greater inter-individual variability in brain development were seen in mid-pubertal individuals, except for a few aspects of white matter development that were more variable between prepubertal individuals in some tracts. Although both sexes contributed to inter-individual differences in macrostructure and functional development in a few regions of the brain, we found limited support for hypotheses regarding greater male-than-female variability. This work highlights pockets of individual variability across facets of early adolescent brain development, while also highlighting regional differences in heterogeneity to facilitate future investigations in quantifying and probing nuances in normative development, and deviations therefrom.

Durham EL, Ghanem K, Stier AJ, Cardenas-Iniguez C, Reimann GE, Jeong HJ, Dupont RM, Dong X, Moore TM, Berman MG, Lahey BB, Bzdok D, Kaczkurkin AN. Multivariate analytical approaches for investigating brain-behavior relationships. Front Neurosci. 2023 Jul 31;17:1175690. doi: 10.3389/fnins.2023.1175690. PMID: 37583413; PMCID: PMC10423877.

Background: Many studies of brain-behavior relationships rely on univariate approaches where each variable of interest is tested independently, which does not allow for the simultaneous investigation of multiple correlated variables. Alternatively, multivariate approaches allow for examining relationships between psychopathology and neural substrates simultaneously. There are multiple multivariate methods to choose from that each have assumptions which can affect the results; however, many studies employ one method without a clear justification for its selection. Additionally, there are few studies illustrating how differences between methods manifest in examining brain-behavior relationships. The purpose of this study was to exemplify how the choice of multivariate approach can change brain-behavior interpretations.

Method: We used data from 9,027 9- to 10-year-old children from the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®) to examine brain-behavior relationships with three commonly used multivariate approaches: canonical correlation analysis (CCA), partial least squares correlation (PLSC), and partial least squares regression (PLSR). We examined the associations between psychopathology dimensions including general psychopathology, attention-deficit/hyperactivity symptoms, conduct problems, and internalizing symptoms with regional brain volumes.

Results: The results of CCA, PLSC, and PLSR showed both consistencies and differences in the relationship between psychopathology symptoms and brain structure. The leading significant component yielded by each method demonstrated similar patterns of associations between regional brain volumes and psychopathology symptoms. However, the additional significant components yielded by each method demonstrated differential brain-behavior patterns that were not consistent across methods.

Conclusion: Here we show that CCA, PLSC, and PLSR yield slightly different interpretations regarding the relationship between child psychopathology and brain volume. In demonstrating the divergence between these approaches, we exemplify the importance of carefully considering the method’s underlying assumptions when choosing a multivariate approach to delineate brain-behavior relationships.

Cui J, Li G, Zhang M, Xu J, Qi H, Ji W, Wu F, Zhang Y, Jiang F, Hu Y, Zhang W, Wei X, Manza P, Volkow ND, Gao X, Wang GJ, Zhang Y. Associations between body mass index, sleep-disordered breathing, brain structure, and behavior in healthy children. Cereb Cortex. 2023 Jul 29:bhad267. doi: 10.1093/cercor/bhad267. Epub ahead of print. PMID: 37522299.

Pediatric overweight/obesity can lead to sleep-disordered breathing (SDB), abnormal neurological and cognitive development, and psychiatric problems, but the associations and interactions between these factors have not been fully explored. Therefore, we investigated the associations between body mass index (BMI), SDB, psychiatric and cognitive measures, and brain morphometry in 8484 children 9-11 years old using the Adolescent Brain Cognitive Development dataset. BMI was positively associated with SDB, and both were negatively correlated with cortical thickness in lingual gyrus and lateral orbitofrontal cortex, and cortical volumes in postcentral gyrus, precentral gyrus, precuneus, superior parietal lobule, and insula. Mediation analysis showed that SDB partially mediated the effect of overweight/obesity on these brain regions. Dimensional psychopathology (including aggressive behavior and externalizing problem) and cognitive function were correlated with BMI and SDB. SDB and cortical volumes in precentral gyrus and insula mediated the correlations between BMI and externalizing problem and matrix reasoning ability. Comparisons by sex showed that obesity and SDB had a greater impact on brain measures, cognitive function, and mental health in girls than in boys. These findings suggest that preventing childhood obesity will help decrease SDB symptom burden, abnormal neurological and cognitive development, and psychiatric problems.

Pearlman AT, Murphy MA, Raiciulescu S, Johnson N, Klein DA, Gray JC, Schvey NA. Longitudinal Associations between Perceived Discrimination and Suicidality in Youth. J Pediatr. 2023 Jul 28:113642. doi: 10.1016/j.jpeds.2023.113642. Epub ahead of print. PMID: 37517645.\

Research among adults reveals robust associations between discrimination and suicidality. The relationship between discrimination and suicidality is understudied in youth. Participants in the Adolescent Brain Cognitive Development (ABCD) study completed a measure of discrimination based on multiple attributes. The Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) was administered one-year later to assess depressive disorders and suicidality (ideation and behavior). Logistic regressions, adjusting for age, sex, race/ethnicity, family income, lifetime depressive disorders, and body composition were conducted. Adjusting for covariates, discrimination based on weight (OR: 2.19), race/ethnicity/color (OR: 3.21), and sexual orientation (OR: 3.83) were associated with greater odds of reporting suicidality one year later (ps < 0.025). Nationality-based discrimination was not significantly associated with suicidality. Compared with those reporting no discrimination, youths reporting discrimination based on two or more attributes had nearly five times greater odds of recent suicidality (OR: 4.72; p<0.001). The current study highlights the deleterious impacts of discrimination on mental health among youths reporting multiple forms of discrimination.

Arnatkeviciute, A., Lemire, M., Morrison, C. et al. Trans-ancestry meta-analysis of genome wide association studies of inhibitory control. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-02187-9

Deficits in effective executive function, including inhibitory control are associated with risk for a number of psychiatric disorders and significantly impact everyday functioning. These complex traits have been proposed to serve as endophenotypes, however, their genetic architecture is not yet well understood. To identify the common genetic variation associated with inhibitory control in the general population we performed the first trans-ancestry genome wide association study (GWAS) combining data across 8 sites and four ancestries (N = 14,877) using cognitive traits derived from the stop-signal task, namely – go reaction time (GoRT), go reaction time variability (GoRT SD) and stop signal reaction time (SSRT). Although we did not identify genome wide significant associations for any of the three traits, GoRT SD and SSRT demonstrated significant and similar SNP heritability of 8.2%, indicative of an influence of genetic factors. Power analyses demonstrated that the number of common causal variants contributing to the heritability of these phenotypes is relatively high and larger sample sizes are necessary to robustly identify associations. In Europeans, the polygenic risk for ADHD was significantly associated with GoRT SD and the polygenic risk for schizophrenia was associated with GoRT, while in East Asians polygenic risk for schizophrenia was associated with SSRT. These results support the potential of executive function measures as endophenotypes of neuropsychiatric disorders. Together these findings provide the first evidence indicating the influence of common genetic variation in the genetic architecture of inhibitory control quantified using objective behavioural traits derived from the stop-signal task.

Westwater, M.L., Mallard, T.T., Warrier, V. et al. Assessing a multivariate model of brain-mediated genetic influences on disordered eating in the ABCD cohort. Nat. Mental Health (2023). https://doi.org/10.1038/s44220-023-00101-4

Eating disorders often emerge during adolescence, and affected individuals frequently demonstrate high rates of psychiatric comorbidity, particularly with depressive and anxiety disorders. Although risk for eating disorders reflects both genetic and neurobiological factors, knowledge of how genetic risk for eating disorders relates to neurobiology and psychiatric symptoms during critical developmental periods remains limited. Here we simultaneously estimated associations between genetic risk, brain structure, and eating-disorder-related psychopathology symptoms in over 4,900 adolescents of European ancestry from the ABCD study (mean age (s.d.) = 9.94 (0.62) years). Polygenic scores for anorexia nervosa (AN PGS) and body mass index (BMI PGS) were related to three morphometric brain features—cortical thickness, surface area, and subcortical gray matter volume—and to latent psychopathology factors using structural equation modeling. We identified a three-factor structure of eating-disorder-related psychopathology symptoms: eating, distress, and fear factors. Increased BMI PGS were uniquely associated with greater eating factor scores. Moreover, greater BMI PGS predicted widespread increases in cortical thickness and reductions in surface area while AN PGS were related to reduced caudate volume. Altered default mode and visual network thickness was associated with greater eating factor scores, whereas distress and fear factor scores reflected a shared reduction in somatomotor network thickness. Our novel findings indicate that greater genetic risk for high BMI and altered cortical thickness of canonical brain networks underpin eating disorder symptomatology in early adolescence. As neurobiological factors appear to shape disordered eating earlier in development than previously thought, these results underscore the need for early detection and intervention efforts for eating disorders.

Yang FN, Picchioni D, Duyn JH. The effect of sleep-corrected social jetlag on crystalized intelligence, school performance, and functional connectome in early adolescence. medRxiv [Preprint]. 2023 Jul 23:2023.07.18.23292833. doi: 10.1101/2023.07.18.23292833. PMID: 37502864; PMCID: PMC10371116.

Approximately half of adolescents encounter a mismatch between their sleep patterns on school days and free days, also referred to as “social jetlag”. This condition has been linked to various adverse outcomes, such as poor sleep, cognitive deficits, and mental disorders. However, prior research was unsuccessful in accounting for other variables that are correlated with social jetlag, including sleep duration and quality. To address this limitation, we applied a propensity score matching method on a sample of 8853 11-12-year-olds from the two-year follow-up (FL2) data of the Adolescent Brain Cognitive Development (ABCD) study. We identified 3366 pairs of participants with high sleep-corrected social jetlag (SJLsc, over 1 hour) and low SJLsc (<= 1 hour) at FL2, as well as 1277 pairs at three-year follow-up (FL3), after matching based on 11 covariates including socioeconomic status, demographics, and sleep duration and quality. Our results showed that high SJLsc, as measured by the Munich Chronotype Questionnaire, was linked to reduced crystallized intelligence, lower school performance – grades, and decreased functional connectivity between cortical networks and subcortical regions, specifically between cingulo-opercular network and right hippocampus (cerc-hprh). Further mediation and longitudinal mediation analyses revealed that cerc-hprh connection mediated the associations between SJLsc and crystallized intelligence at FL2, and between SJLsc and grades at both FL2 and FL3. We validated these findings by replicating these results using objective SJLsc measurements obtained via Fitbit watches. Overall, our study highlights the negative association between social jetlag and crystallized intelligence during early adolescence.

Cortez CA, Yuefan Shao I, Seamans MJ, Dooley EE, Pettee Gabriel K, Nagata JM. Moderate-to-vigorous intensity physical activity among U.S. adolescents before and during the COVID-19 pandemic: Findings from the Adolescent Brain Cognitive Development Study. Prev Med Rep. 2023 Jul 23;35:102344. doi: 10.1016/j.pmedr.2023.102344. PMID: 37564120; PMCID: PMC10410239.

Li Y, Ma X, Sunderraman R, Ji S, Kundu S. Accounting for temporal variability in functional magnetic resonance imaging improves prediction of intelligence. Hum Brain Mapp. 2023 Jul 19. doi: 10.1002/hbm.26415. Epub ahead of print. PMID: 37466292.

Neuroimaging-based prediction methods for intelligence have seen a rapid development. Among different neuroimaging modalities, prediction using functional connectivity (FC) has shown great promise. Most literature has focused on prediction using static FC, with limited investigations on the merits of such analysis compared to prediction using dynamic FC or region-level functional magnetic resonance imaging (fMRI) times series that encode temporal variability. To account for the temporal dynamics in fMRI, we propose a bi-directional long short-term memory (bi-LSTM) approach that incorporates feature selection mechanism. The proposed pipeline is implemented via an efficient algorithm and applied for predicting intelligence using region-level time series and dynamic FC. We compare the prediction performance using different fMRI features acquired from the Adolescent Brain Cognitive Development (ABCD) study involving nearly 7000 individuals. Our detailed analysis illustrates the consistently inferior performance of static FC compared to region-level time series or dynamic FC for single and combined rest and task fMRI experiments. The joint analysis of task and rest fMRI leads to improved intelligence prediction under all models compared to using fMRI from only one experiment. In addition, the proposed bi-LSTM pipeline based on region-level time series identifies several shared and differential important brain regions across fMRI experiments that drive intelligence prediction. A test-retest analysis of the selected regions shows strong reliability across cross-validation folds. Given the large sample size of ABCD study, our results provide strong evidence that superior prediction of intelligence can be achieved by accounting for temporal variations in fMRI.

Mattoni M, Hopman HJ, Dadematthews A, Chan SSM, Olino TM. Specificity of associations between parental psychopathology and offspring brain structure. Psychiatry Res Neuroimaging. 2023 Jul 17;334:111684. doi: 10.1016/j.pscychresns.2023.111684. Epub ahead of print. PMID: 37499380

Multiple forms of parental psychopathology have been associated with differences in subcortical brain volume. However, few studies have considered the role of comorbidity. Here, we examine if alterations in child subcortical brain structure are specific to parental depression, anxiety, mania, or alcohol/substance use parental psychopathology, common across these disorders, or altered by a history of multiple disorders. We examined 6581 children aged 9 to 10 years old from the ABCD study with no history of mental disorders. We found several significant interactions such that the effects of a parental history of depression, anxiety, and substance use problems on amygdala and striatal volumes were moderated by comorbid parental history of another disorder. Interactions tended to suggest smaller volumes in the presence of a comorbid disorder. However, effect sizes were small, and no associations remained significant after correcting for multiple comparisons. Results suggest that associations between familial risk for psychopathology and offspring brain structure in 9-10-year-olds are modest, and relationships that do exist tend to implicate the amygdala and striatal regions and are moderated by a comorbid parental psychopathology history. Several methodological factors, including controlling for intracranial volume and other forms of parental psychopathology and excluding child psychopathology, likely contribute to inconsistencies in the literature.

Estévez-López F, Kim HH, López-Vicente M, Legerstee JS, Hillegers MHJ, Tiemeier H, Muetzel RL. Physical symptoms and brain morphology: a population neuroimaging study in 12,286 pre-adolescents. Transl Psychiatry. 2023 Jul 12;13(1):254. doi: 10.1038/s41398-023-02528-w. PMID: 37438345.

Physical symptoms, also known as somatic symptoms, are those for which medical examinations do not reveal a sufficient underlying root cause (e.g., pain and fatigue). The extant literature of the neurobiological underpinnings of physical symptoms is largely inconsistent and primarily comprises of (clinical) case-control studies with small sample sizes. In this cross-sectional study, we studied the association between dimensionally measured physical symptoms and brain morphology in pre-adolescents from two population-based cohorts; the Generation R Study (n = 2649, 10.1 ± 0.6 years old) and ABCD Study (n = 9637, 9.9 ± 0.6 years old). Physical symptoms were evaluated using continuous scores from the somatic complaints syndrome scale from the parent-reported Child Behavior Checklist (CBCL). High-resolution structural magnetic resonance imaging (MRI) was collected using 3-Tesla MRI systems. Linear regression models were fitted for global brain metrics (cortical and subcortical grey matter and total white matter volume) and surface-based vertex-wise measures (surface area and cortical thickness). Results were meta-analysed. Symptoms of anxiety/depression were studied as a contrasting comorbidity. In the meta-analyses across cohorts, we found negative associations between physical symptoms and surface area in the (i) left hemisphere; in the lateral orbitofrontal cortex and pars triangularis and (ii) right hemisphere; in the pars triangularis, the pars orbitalis, insula, middle temporal gyrus and caudal anterior cingulate cortex. However, only a subset of regions (left lateral orbitofrontal cortex and right pars triangularis) were specifically associated with physical symptoms, while others were also related to symptoms of anxiety/depression. No significant associations were observed for cortical thickness. This study in preadolescents, the most representative and well-powered to date, showed that more physical symptoms are modestly related to less surface area of the prefrontal cortex mostly. While these effects are subtle, future prospective research is warranted to understand the longitudinal relationship of physical symptoms and brain changes over time. Particularly, to elucidate whether physical symptoms are a potential cause or consequence of distinct neurodevelopmental trajectories.

Ma J, McGlade EC, Huber RS, Lyoo IK, Renshaw PF, Yurgelun-Todd DA. Overweight/Obesity-related microstructural alterations of the fimbria-fornix in the ABCD study: The role of aerobic physical activity. PLoS One. 2023 Jul 12;18(7):e0287682. doi: 10.1371/journal.pone.0287682. PMID: 37437033; PMCID: PMC10337868.

Childhood overweight/obesity has been associated with negative consequences related to brain function and may involve alterations in white matter pathways important for cognitive and emotional processing. Aerobic physical activity is a promising lifestyle factor that could restore white matter alterations. However, little is known about either regional white matter alterations in children with overweight/obesity or the effects of aerobic physical activity targeting the obesity-related brain alterations in children. Using a large-scale cross-sectional population-based dataset of US children aged 9 to 10 years (n = 8019), this study explored the associations between overweight/obesity and microstructure of limbic white matter tracts, and examined whether aerobic physical activity may reduce the overweight/obesity-related white matter alterations in children. The primary outcome measure was restriction spectrum imaging (RSI)-derived white matter microstructural integrity measures. The number of days in a week that children engaged in aerobic physical activity for at least 60 minutes per day was assessed. We found that females with overweight/obesity had lower measures of integrity of the fimbria-fornix, a major limbic-hippocampal white matter tract, than their lean peers, while this difference was not significant in males. We also found a positive relationship between the number of days of aerobic physical activity completed in a week and integrity measures of the fimbria-fornix in females with overweight/obesity. Our results provide cross-sectional evidence of sex-specific microstructural alteration in the fimbria-fornix in children with overweight/obesity and suggest that aerobic physical activity may play a role in reducing this alteration. Future work should examine the causal direction of the relationship between childhood overweight/obesity and brain alterations and evaluate potential interventions to validate the effects of aerobic physical activity on this relationship.

Nishat E, Stojanovski S, Scratch SE, Ameis SH, Wheeler AL. Premature white matter microstructure in female children with a history of concussion. Dev Cogn Neurosci. 2023 Jul 7;62:101275. doi: 10.1016/j.dcn.2023.101275. Epub ahead of print. PMID: 37441978.

Childhood concussion may interfere with neurodevelopment and influence cognition. Females are more likely to experience persistent symptoms after concussion, yet the sex-specific impact of concussion on brain microstructure in children is understudied. This study examined white matter and cortical microstructure, based on neurite density (ND) from diffusion-weighted MRI, in 9-to-10-year-old children in the Adolescent Brain Cognitive Development Study with (n = 336) and without (n = 7368) a history of concussion, and its relationship with cognitive performance. Multivariate regression was used to investigate relationships between ND and group, sex, and age in deep and superficial white matter, subcortical structures, and cortex. Partial least square correlation was performed to identify associations between ND and performance on NIH Toolbox tasks in children with concussion. All tissue types demonstrated higher ND with age, reflecting brain maturation. Group comparisons revealed higher ND in deep and superficial white matter in females with concussion. In female but not male children with concussion, there were significant associations between ND and performance on cognitive tests. These results demonstrate a greater long-term impact of childhood concussion on white matter microstructure in females compared to males that is associated with cognitive function. The increase in ND in females may reflect premature white matter maturation.

Bhatia D, Lewis B, Farrior H, Moore A, Nixon SJ. Substance familiarity in middle childhood and adolescent substance use. Drug Alcohol Depend. 2023 Jul 7;250:110892. doi: 10.1016/j.drugalcdep.2023.110892. Epub ahead of print. PMID: 37473699.

Background: Childhood familiarity with (knowledge of) substances is a potentially important, currently understudied adolescent substance use risk factor. We aimed to describe changes in childhood familiarity with substances and to test whether baseline familiarity predicts early adolescent substance use.

Methods: Utilizing the Substance Use Module of the longitudinal cohort study, Adolescent Brain Cognitive Development (ABCD; US youth aged 9-10 years followed for 10 years) through Data Release 4 (n=7896; individuals who completed all six assessments in the first three years), we conducted longitudinal mixed models and survival analyses to describe changes in familiarity and to determine the adjusted odds of substance use by age 13 based on number of familiar substances at baseline.

Results: The sample consisted of 3754 females and 4142 males, aged 9-10 at baseline, with majority White individuals (68.9%). Unconditional time models indicated age significantly predicted familiarity (B=0.08, p<0.001; R2=0.288) with ~3.59 familiar substances at 9 years increasing to ~7.43 substances at 13 years. Family history, home use, peer use, and neighborhood availability predicted familiarity, accounting for 1% of additional variance (R2=0.299; ∆R2=0.011). For each additional familiar substance at baseline, adjusted odds of future use increased 1.28 times (95% CI 1.22, 1.34).

Conclusions: This is the first study to characterize substance familiarity in this age range as a predictor of future substance use. Familiarity increases with age (age being the most predictive indicator). Familiarity at age 9-10 predicts early adolescent substance use. As such, childhood familiarity may represent an easily implemented screening tool for at-risk youth.

Orendain N, Anderson A, Galván A, Bookheimer S, Chung PJ. A data-driven approach to categorizing early life adversity exposure in the ABCD Study. BMC Med Res Methodol. 2023 Jul 7;23(1):164. doi: 10.1186/s12874-023-01983-9. PMID: 37420169; PMCID: PMC10327383.

Background
Adversity occurring during development is associated with detrimental health and quality of life outcomes, not just following exposure but throughout the lifespan. Despite increased research, there exists both overlapping and distinct definitions of early life adversity exposure captured by over 30 different empirically validated tools. A data-driven approach to defining and cataloging exposure is needed to better understand associated outcomes and advance the field.

Methods
We utilized baseline data on 11,566 youth enrolled in the ABCD Study to catalog youth and caregiver-reported early life adversity exposure captured across 14 different measures. We employed an exploratory factor analysis to identify the factor domains of early life adversity exposure and conducted a series of regression analyses to examine its association with problematic behavioral outcomes.

Results
The exploratory factor analysis yielded a 6-factor solution corresponding to the following distinct domains: 1) physical and sexual violence; 2) parental psychopathology; 3) neighborhood threat; 4) prenatal substance exposure; 5) scarcity; and 6) household dysfunction. The prevalence of exposure among 9-and 10-year-old youth was largely driven by the incidence of parental psychopathology. Sociodemographic characteristics significantly differed between youth with adversity exposure and controls, depicting a higher incidence of exposure among racial and ethnic minoritized youth, and among those identifying with low socioeconomic status. Adversity exposure was significantly associated with greater problematic behaviors and largely driven by the incidence of parental psychopathology, household dysfunction and neighborhood threat. Certain types of early life adversity exposure were more significantly associated with internalizing as opposed to externalizing problematic behaviors.

Conclusions
We recommend a data-driven approach to define and catalog early life adversity exposure and suggest the incorporation of more versus less data to capture the nuances of exposure, e.g., type, age of onset, frequency, duration. The broad categorizations of early life adversity exposure into two domains, such as abuse and neglect, or threat and deprivation, fail to account for the routine co-occurrence of exposures and the duality of some forms of adversity. The development and use of a data-driven definition of early life adversity exposure is a crucial step to lessening barriers to evidence-based treatments and interventions for youth.

Kaplan CM, Schrepf A, Boehnke KF, He Y, Smith T, Williams DA, Bergmans R, Voepel-Lewis T, Hassett AL, Harris RE, Clauw DJ, Beltz AM, Harte SE. Risk Factors for the Development of Multisite Pain in Children. Clin J Pain. 2023 Jul 6. doi: 10.1097/AJP.0000000000001148. Epub ahead of print. PMID: 37440345.

Objective: Chronic pain has economic costs on par with cardiovascular disease, diabetes, and cancer. Despite this impact on the health care system and an increasing awareness of the relationship between pain and mortality, efforts to identify simple symptom-based risk factors for the development of pain, particularly in children, have fallen short. This is critically important as pain that manifests during childhood often persists into adulthood. To date no longitudinal studies have examined symptoms in pain-free children that presage a new, multisite manifestation of pain in the future. We hypothesized that female sex, sleep problems and heightened somatic complaints at baseline would be associated with the risk of developing new multisite pain one year later.

Methods: Symptom assessments were completed by parents of youth (ages 9-10) enrolled in the Adolescent Brain Cognitive Development study. Multivariate logistic regression models focused on children who developed multisite pain one year later (n=331) and children who remained pain-free (n=3335) .

Results: Female sex (OR=1.35; 95% CI=1.07, 1.71; P=0.01) , elevated non-painful somatic complaints (OR=1.17; 95% CI=1.06, 1.29; P<0.01) , total sleep problems (OR=1.20; 95% CI=1.07, 1.34; P< 0.01) , and attentional issues (OR=1.22; 95% CI=1.10, 1.35; P<0.001) at baseline were associated with new multisite pain one year later. Baseline negative affect was not associated with new multisite pain.

Discussion: Identifying symptom-based risk factors for multisite pain in children is critical for early prevention. Somatic awareness, sleep and attention problems represent actionable targets for early detection, treatment, and possible prevention of multisite pain in youth.

Gordon JH, Tran KT, Visoki E, Argabright S, DiDomenico GE, Saiegh E, Hoffman KW, Erez G, Barzilay R. The Role of Individual Discrimination and Structural Stigma in the Mental Health of Sexual Minority Youth. J Am Acad Child Adolesc Psychiatry. 2023 Jul 5:S0890-8567(23)00375-1. doi: 10.1016/j.jaac.2023.05.033. Epub ahead of print. PMID: 37422106.

Objective: Sexual minority (SM) youth experience greater mental health burden compared to their heterosexual peers. The aims of the present study were to (1) characterize mental health disparities among SM compared to non-SM youth, (2) test main and interactive associations of SM identity and stressors targeting SM youth at the individual-level (interpersonal-SM-discrimination) and structural-level (state-level structural-SM-stigma) with youth mental health, and (3) explore the contribution of interpersonal-SM-discrimination to the mental health burden of SM youth.

Method: Participants were N=11,622 youth (ages 9-13, 47.6% assigned-female-at-birth) from the Adolescent Brain Cognitive Development (ABCD) Study. Linear mixed-effects models tested main and interactive associations of SM identity, interpersonal-SM-discrimination, and structural-SM-stigma with mental health measures (self-reported overall psychopathology, suicidal ideation, and suicide attempts), adjusting for demographics and other interpersonal stressors not specific to SM (other discrimination types, peer victimization and cyberbullying). Longitudinal mediation models tested whether interpersonal-SM-discrimination mediated the associations between SM identity and mental health measures.

Results: SM youth (n=1,051) experienced more interpersonal-SM-discrimination and overall psychopathology compared to their non-SM peers (n=10,571). There were significant associations (main effects) of interpersonal-SM-discrimination and structural-SM stigma with overall psychopathology adjusting for demographics. When further adjusting for other non-SM related stressors, main effect of structural-SM-stigma was no longer significant. Interpersonal-SM-discrimination was also significantly associated with suicidal ideation and attempt accounting for demographics, while structural-SM-stigma was not. Accounting for both demographics and other non-SM stressors, there was a significant interaction between SM identity and structural-SM-stigma in association with psychopathology (P=0.02), such that, compared to their peers, SM youth showed a greater association between structural-SM-stigma and psychopathology. Longitudinal mediation revealed that interpersonal-SM-discrimination was a significant mediator explaining ∼10-15% of the variance of the pathways between SM identity and all mental health outcomes.

Conclusion: Results delineate contributions of interpersonal discrimination and structural stigma targeting SM to their heightened mental health burden in early adolescence. Findings underscore the need to address microlevel and macrolevel SM-discrimination and structural stigma when caring for this population.

Cuevas AG, Krobath DM, Rhodes-Bratton B, Xu S, Omolade JJ, Perry AR, Slopen N. Association of Racial Discrimination With Adiposity in Children and Adolescents. JAMA Netw Open. 2023 Jul 3;6(7):e2322839. doi: 10.1001/jamanetworkopen.2023.22839. PMID: 37432683.

Importance: Childhood obesity is a major public health issue and is disproportionately prevalent among children from minority racial and ethnic groups. Personally mediated racism (commonly referred to as racial discrimination) is a known stressor that has been linked to higher body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) in adults, but little is known about the association of racial discrimination and childhood and adolescent adiposity.

Objective: To assess the prospective association between self-reported experiences of racial discrimination and adiposity (BMI and waist circumference) in a large sample of children and adolescents in the Adolescent Brain Cognitive Development (ABCD) study.

Design, setting, and participants: This cohort study used complete data from the ABCD study (2017 to 2019), involving a total of 6463 participants. The ABCD study recruited a diverse sample of youths from across the US, with rural, urban, and mountain regions. Data were analyzed from January 12 to May 17, 2023.

Exposure: The child-reported Perceived Discrimination Scale was used to quantify racial discrimination, reflecting participants’ perceptions of being treated unfairly by others or unaccepted by society based on their race or ethnicity.

Main outcomes and measures: Weight, height, and waist circumference were measured by trained research assistants. BMI z scores were computed by applying the US Centers for Disease Control and Prevention’s age and sex-specific reference standards for children and adolescents. Waist circumference (inches) was quantified as the mean of 3 consecutive measures. Measurements were taken from time 1 (ie, 2017 to 2019) and time 2 (ie, 2018 to 2020).

Results: Of the 6463 respondents with complete data, 3090 (47.8%) were female, and the mean (SD) age was 9.95 (0.62) years. Greater racial discrimination exposure at time 1 was associated with higher BMI z score in both unadjusted (β, 0.05; 95% CI, 0.02-0.08) and adjusted regression models (β, 0.04; 95% CI, 0.01-0.08). Discrimination at time 1 was associated with higher waist circumference in unadjusted (β, 0.35; 95% CI, 0.15-0.54) and adjusted (β, 0.24; 95% CI, 0.04-0.44) models.

Conclusions and relevance: In this cohort study of children and adolescents, racial discrimination was positively associated with adiposity, quantified by BMI z score and waist circumference. Interventions to reduce exposure to racial discrimination in early life may help reduce the risk of excess weight gain across throughout life.

Weiss NH, Goncharenko S, Forkus SR, Ferguson JJ, Yang M. Longitudinal Investigation of Bidirectional Relations Between Childhood Trauma and Emotion-Driven Impulsivity in the Adolescent Brain Cognitive Development Study. J Adolesc Health. 2023 Jul 3:S1054-139X(23)00302-6. doi: 10.1016/j.jadohealth.2023.05.027. Epub ahead of print. PMID: 37410001.

Objective: Exposure to childhood trauma is associated with numerous adverse mental health consequences. Addressing important gaps in the existing research, the proposed study clarifies the longitudinal and bidirectional associations between childhood trauma and both negative and positive emotion-driven impulsivity.

Method: This study utilized a sample of 11,872 9- to 10-years-olds recruited from 21 research sites across the United States from the Adolescent Brain Cognitive Ddevelopment (ABCD) Study. Childhood trauma was assessed at one- and two-year follow-ups. Negative and positive urgency were assessed at baseline and two-year follow-up. Cross-lagged panel models evaluated the longitudinal and bidirectional associations between childhood trauma and both negative and positive emotion-driven impulsivity.

Results: Findings showed that earlier childhood trauma was associated with higher levels of later negative (β = 0.133, p < .001) and positive (β = 0.125, p < .001) emotion-driven impulsivity. Further, higher levels of earlier positive (β = 0.033, p < .006), but not negative (β = 0.010, p = .405), emotion-driven impulsivity were associated with later childhood trauma. Finally, the strength of the relations between childhood trauma and emotion-driven impulsivity did not differ by sex (ΔX2 = 10.228, p > .05).

Discussion: Identification of both negative and positive emotion-driven impulsivity among children exposed to trauma may serve as a point of intervention to reduce subsequent risk for deleterious health outcomes.

Shen C, Rolls ET, Xiang S, et al. Brain and molecular mechanisms underlying the nonlinear association between close friendships, mental health, and cognition in children. eLife, Jul 3, 2023. https://doi.org/10.7554/eLife.84072.

Close friendships are important for mental health and cognition in late childhood. However, whether the more close friends the better, and the underlying neurobiological mechanisms are unknown. Using the Adolescent Brain Cognitive Developmental study, we identified nonlinear associations between the number of close friends, mental health, cognition, and brain structure. Although few close friends were associated with poor mental health, low cognitive functions, and small areas of the social brain (e.g., the orbitofrontal cortex, the anterior cingulate cortex, the anterior insula, and the temporoparietal junction), increasing the number of close friends beyond a level (around 5) was no longer associated with better mental health and larger cortical areas, and was even related to lower cognition. In children having no more than five close friends, the cortical areas related to the number of close friends revealed correlations with the density of μ-opioid receptors and the expression of OPRM1 and OPRK1 genes, and could partly mediate the association between the number of close friends, attention-deficit/hyperactivity disorder (ADHD) symptoms, and crystalized intelligence. Longitudinal analyses showed that both too few and too many close friends at baseline were associated with more ADHD symptoms and lower crystalized intelligence 2 y later. Additionally, we found that friendship network size was nonlinearly associated with well-being and academic performance in an independent social network dataset of middle-school students. These findings challenge the traditional idea of ‘the more, the better,’ and provide insights into potential brain and molecular mechanisms.

Ortin-Peralta A, Sheftall AH, Osborn A, Miranda R. Severity and Transition of Suicidal Behaviors in Childhood: Sex, Racial, and Ethnic Differences in the Adolescent Brain Cognitive Development (ABCD) Study. J Adolesc Health. 2023 Jun 30:S1054-139X(23)00285-9. doi: 10.1016/j.jadohealth.2023.05.026. Epub ahead of print. PMID: 37389520.

Purpose: To examine the prevalence, incidence, and transitions of suicide ideation and attempts and sex and racial/ethnic differences among children enrolled in three yearly assessments of the Adolescent Brain Cognitive Development Study. The forms of suicidal ideation (SI) (no SI, passive, nonspecific active, and active) among those who attempted suicide were also described.

Methods: A subsample of 9,923 children (9-10 years old at baseline, 48.6% female) completed the KSADS-5 questions about suicide ideation and attempts in three yearly assessment (83.5% of baseline sample).

Results: Almost 18% of the children reported suicidal ideation and 2.2% a suicide attempt at one of the three assessments. Passive (6.9%) and nonspecific active (6.4%) were the most frequent forms of suicidal ideation reported. Of the children with suicidal ideation at baseline, 5.9% first attempted suicide in the two subsequent years. Boys (vs. girls) reported more suicidal ideation at baseline. Black children (vs. White and Hispanic/Latinx) and girls (vs. boys) were more likely to start thinking about suicide over time. Black children (vs. White) reported more suicide attempts at baseline and across assessments. More than half of the children who attempted suicide at any assessment reported nonspecific active suicidal ideation (desire to kill oneself without plan/intent/method) as the most severe form of ideation.

Discussion: Findings suggest a high prevalence of suicidal ideation among children in the US. When conducting risk assessments, clinicians should consider both active and nonspecific active suicidal ideation. Early intervention with children who are thinking about suicide may reduce their risk for attempting suicide.

van Dijk MT, Talati A, Kashyap P, Desai K, Kelsall N, Gameroff M, Aw N, Abraham E, Cullen B, Cha J, Anacker C, Weissman MM, Posner J. Dentate Gyrus Microstructure is associated with Resilience after Exposure to Maternal Stress Across Two Human Cohorts. Biol Psychiatry. 2023 Jun 29:S0006-3223(23)01399-9. doi: 10.1016/j.biopsych.2023.06.026. Epub ahead of print. PMID: 37393047.

Background: Maternal stress (MS) is a well-documented risk factor for impaired emotional development in offspring. Rodent models implicate the dentate gyrus (DG) of the hippocampus in the effects of MS on offspring depressive-like behaviors, but mechanisms in humans remain unclear. Here, we test across two independent cohorts whether MS is associated with depressive symptoms and with DG micro- and macro-structural alterations in offspring.

Methods: We analyzed DG DTI mean diffusivity (DG-MD) and volume in a 3-Generation Family Risk for Depression study (TGS; n=69, mean age 35.0) and the Adolescent Brain Cognitive Development Study (ABCD; n=5196, mean age 9.9) using generalized estimating equation models and mediation analysis. MS was assessed by the Parenting Stress Index (in TGS) and a measure compiled from the Adult Response Survey (ABCD). PHQ-9 and rumination scales (TGS) and Child Behavior Checklist (ABCD) measured offspring depressive symptoms at follow-up. Schedule for Affective Disorders and Schizophrenia-Lifetime interview measured depression diagnoses.

Results: Across cohorts, MS was associated with future symptoms and higher DG-MD (indicating disrupted microstructure) in offspring. Higher DG-MD was associated with higher symptom scores measured 5 years (TGS) and 1-year (ABCD) after MRI. In ABCD, DG-MD is increased in high-MS offspring who have depressive symptoms at follow-up, but not in offspring who remain resilient or whose mother had low MS.

Conclusions: Converging results across two independent samples extend previous rodent studies and suggest a role for the DG in exposure to MS and offspring depression.

Petrican R, Fornito A, Boyland E. Lifestyle Factors Counteract the Neurodevelopmental Impact of Genetic Risk for Accelerated Brain Aging in Adolescence. Biol Psychiatry. 2023 Jun 29:S0006-3223(23)01396-3. doi: 10.1016/j.biopsych.2023.06.023. Epub ahead of print. PMID: 37393046.

Background: The transition from childhood to adolescence is characterised by enhanced neural plasticity and a consequent susceptibility to both beneficial and adverse aspects of one’s milieu.

Methods: To understand the implications of the interplay between protective and risk-enhancing factors, we analysed longitudinal data from the Adolescent Brain and Cognitive Development study (N = 834; 394 female). We probed the maturational correlates of positive lifestyle variables (friendships, parental warmth, school engagement, physical exercise, healthy nutrition) and of genetic vulnerability to neuropsychiatric disorders (Major Depressive Disorder, Alzheimer’s Disease, Anxiety Disorders, Bipolar Disorder, Schizophrenia), and further sought to elucidate their implications for psychological well-being.

Results: Genetic risk factors and lifestyle buffers showed divergent relationships with later attentional and interpersonal problems. These effects were mediated by distinguishable functional neurodevelopmental deviations spanning the limbic, default mode, visual and control systems. Specifically, greater genetic vulnerability was associated with alterations in the normative maturation of areas rich in dopamine (D2), glutamate and serotonin receptors, and of areas with stronger expression of astrocytic and microglial genes, a molecular signature implicated in the brain disorders discussed here. Greater availability of lifestyle buffers predicted deviations in the normative functional development of higher density GABA-ergic receptor regions. The two profiles of neurodevelopmental alterations showed complementary roles in protection against psychopathology, which varied with environmental stress levels.

Conclusions: Our results underscore the importance of educational involvement and healthy nutrition in attenuating the neurodevelopmental sequelae of genetic risk factors. They also underscore the importance of characterising early life biomarkers associated with adult-onset pathologies.

Sun YJ, Sahakian BJ, Langley C, Yang A, Jiang Y, Kang J, Zhao X, Li C, Cheng W, Feng J. Early-initiated childhood reading for pleasure: associations with better cognitive performance, mental well-being and brain structure in young adolescence. Psychol Med. 2023 Jun 28:1-15. doi: 10.1017/S0033291723001381. Epub ahead of print. PMID: 37376848.

Background: Childhood is a crucial neurodevelopmental period. We investigated whether childhood reading for pleasure (RfP) was related to young adolescent assessments of cognition, mental health, and brain structure.

Methods: We conducted a cross-sectional and longitudinal study in a large-scale US national cohort (10 000 + young adolescents), using the well-established linear mixed model and structural equation methods for twin study, longitudinal and mediation analyses. A 2-sample Mendelian randomization (MR) analysis for potential causal inference was also performed. Important factors including socio-economic status were controlled.

Results: Early-initiated long-standing childhood RfP (early RfP) was highly positively correlated with performance on cognitive tests and significantly negatively correlated with mental health problem scores of young adolescents. These participants with higher early RfP scores exhibited moderately larger total brain cortical areas and volumes, with increased regions including the temporal, frontal, insula, supramarginal; left angular, para-hippocampal; right middle-occipital, anterior-cingulate, orbital areas; and subcortical ventral-diencephalon and thalamus. These brain structures were significantly related to their cognitive and mental health scores, and displayed significant mediation effects. Early RfP was longitudinally associated with higher crystallized cognition and lower attention symptoms at follow-up. Approximately 12 h/week of youth regular RfP was cognitively optimal. We further observed a moderately significant heritability of early RfP, with considerable contribution from environments. MR analysis revealed beneficial causal associations of early RfP with adult cognitive performance and left superior temporal structure.

Conclusions: These findings, for the first time, revealed the important relationships of early RfP with subsequent brain and cognitive development and mental well-being.

Gaus R, Pölsterl S, Greimel E, Schulte-Körne G, Wachinger C. Can we diagnose mental disorders in children? A large-scale assessment of machine learning on structural neuroimaging of 6916 children in the adolescent brain cognitive development study. JCPP Adv. 2023 Jun 28;3(4):e12184. doi: 10.1002/jcv2.12184. PMID: 38054056; PMCID: PMC10694548.

Background: Prediction of mental disorders based on neuroimaging is an emerging area of research with promising first results in adults. However, research on the unique demographic of children is underrepresented and it is doubtful whether findings obtained on adults can be transferred to children.

Methods: Using data from 6916 children aged 9-10 in the multicenter Adolescent Brain Cognitive Development study, we extracted 136 regional volume and thickness measures from structural magnetic resonance images to rigorously evaluate the capabilities of machine learning to predict 10 different psychiatric disorders: major depressive disorder, bipolar disorder (BD), psychotic symptoms, attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, post-traumatic stress disorder, obsessive-compulsive disorder, generalized anxiety disorder, and social anxiety disorder. For each disorder, we performed cross-validation and assessed whether models discovered a true pattern in the data via permutation testing.

Results: Two of 10 disorders can be detected with statistical significance when using advanced models that (i) allow for non-linear relationships between neuroanatomy and disorder, (ii) model interdependencies between disorders, and (iii) avoid confounding due to sociodemographic factors: ADHD (AUROC = 0.567, p = 0.002) and BD (AUROC = 0.551, p = 0.002). In contrast, traditional models perform consistently worse and predict only ADHD with statistical significance (AUROC = 0.529, p = 0.002).

Conclusion: While the modest absolute classification performance does not warrant application in the clinic, our results provide empirical evidence that embracing and explicitly accounting for the complexities of mental disorders via advanced machine learning models can discover patterns that would remain hidden with traditional models.

Cotter DL, Campbell CE, Sukumaran K, McConnell R, Berhane K, Schwartz J, Hackman DA, Ahmadi H, Chen JC, Herting MM. Effects of ambient fine particulates, nitrogen dioxide, and ozone on maturation of functional brain networks across early adolescence. Environ Int. 2023 Jul;177:108001. doi: 10.1016/j.envint.2023.108001. Epub 2023 Jun 1. PMID: 37307604; PMCID: PMC10353545.

Background: Air pollution is linked to neurodevelopmental delays, but its association with longitudinal changes in brain network development has yet to be investigated. We aimed to characterize the effect of PM2.5, O3, and NO2 exposure at ages 9-10 years on changes in functional connectivity (FC) over a 2-year follow-up period, with a focus on the salience (SN), frontoparietal (FPN), and default-mode (DMN) brain networks as well as the amygdala and hippocampus given their importance in emotional and cognitive functioning.

Methods: A sample of children (N = 9,497; with 1-2 scans each for a total of 13,824 scans; 45.6% with two brain scans) from the Adolescent Brain Cognitive Development (ABCD) Study® were included. Annual averages of pollutant concentrations were assigned to the child’s primary residential address using an ensemble-based exposure modeling approach. Resting-state functional MRI was collected on 3T MRI scanners. First, developmental linear mixed-effect models were performed to characterize typical FC development within our sample. Next, single- and multi-pollutant linear mixed-effect models were constructed to examine the association between exposure and intra-network, inter-network, and subcortical-to-network FC change over time, adjusting for sex, race/ethnicity, income, parental education, handedness, scanner type, and motion.

Results: Developmental profiles of FC over the 2-year follow-up included intra-network integration within the DMN and FPN as well as inter-network integration between the SN-FPN; along with intra-network segregation in the SN as well as subcortical-to-network segregation more broadly. Higher PM2.5 exposure resulted in greater inter-network and subcortical-to-network FC over time. In contrast, higher O3 concentrations resulted in greater intra-network, but less subcortical-to-network FC over time. Lastly, higher NO2 exposure led to less inter-network and subcortical-to-network FC over the 2-year follow-up period.

Conclusion: Taken together, PM2.5, O3, and NO2 exposure in childhood relate to distinct changes in patterns of network maturation over time. This is the first study to show outdoor ambient air pollution during childhood is linked to longitudinal changes in brain network connectivity development.

Yang B, Anderson Z, Zhou Z, Liu S, Haase CM, Qu Y. The Unique and Interactive Roles of Neural Reward Sensitivity and Family Conflict in Predicting Youth’s Internalizing Problems: A Biopsychosocial Approach. Psychoneuroendocrinology. Volume 153, Supplement, July 2023, 106253, https://doi.org/10.1016/j.psyneuen.2023.106253

Background
Adolescence is a period marked by heightened neural sensitivity to reward, which is associated with less internalizing problems (Hanson et al., 2015; Ng et al., 2019). However, it remains unknown how reward sensitivity may interact with family environment in predicting youth’s internalizing problems. Therefore, the current research took a biopsychosocial approach to examine this question.

Methods
Data were obtained from baseline (T1) and one-year follow-up (T2) of the ABCD study. At T1, youth (N = 8762; mean age = 9.93 years; 51% boys) completed the Monetary Incentive Delay task during fMRI scanning, which measured neural activity during reward processing. Moreover, family conflict at T1 and youth’s internalizing problems at T1 and T2 were assessed.

Results
Youth’s ventral striatum activity during reward receipt at T1 predicted fewer internalizing problems at T2, controlling for internalizing problems at T1 and demographic covariates. Family conflict at T1 predicted youth’s more internalizing problems over time. Importantly, there was an interaction effect between ventral striatum activity and family conflict. When family conflict was low, greater neural sensitivity to reward predicted youth’s fewer internalizing problems over time; in contrast, youth from high-conflict families showed high levels of internalizing problems regardless of reward sensitivity.

Conclusion
The findings suggest that adverse family environments hinder the positive role of reward sensitivity in youth’s psychological adjustment. Given that youth typically show heightened sensitivity to reward, it is crucial to cultivate a supportive family environment where youth have enough exposure to social rewards from family members instead of stress or conflict.

Ji W, Li G, Jiang F, Zhang Y, Wu F, Zhang W, Hu Y, Wang J, Wei X, Li Y, Manza P, Tomasi D, Gao X, Wang GJ, Zhang Y, Volkow ND. Preterm birth associated alterations in brain structure, cognitive functioning and behavior in children from the ABCD dataset. Psychol Med. 2023 Jun 27:1-10. doi: 10.1017/S0033291723001757. Epub ahead of print. PMID: 37365781.

Background: Preterm birth is a global health problem and associated with increased risk of long-term developmental impairments, but findings on the adverse outcomes of prematurity have been inconsistent.

Methods: Data were obtained from the baseline session of the ongoing longitudinal Adolescent Brain and Cognitive Development (ABCD) Study. We identified 1706 preterm children and 1865 matched individuals as Control group and compared brain structure (MRI data), cognitive function and mental health symptoms.

Results: Results showed that preterm children had higher psychopathological risk and lower cognitive function scores compared to controls. Structural MRI analysis indicated that preterm children had higher cortical thickness in the medial orbitofrontal cortex, parahippocampal gyrus, temporal and occipital gyrus; smaller volumes in the temporal and parietal gyrus, cerebellum, insula and thalamus; and smaller fiber tract volumes in the fornix and parahippocampal-cingulum bundle. Partial correlation analyses showed that gestational age and birth weight were associated with ADHD symptoms, picvocab, flanker, reading, fluid cognition composite, crystallized cognition composite and total cognition composite scores, and measures of brain structure in regions involved with emotional regulation, attention and cognition.

Conclusions: These findings suggest a complex interplay between psychopathological risk and cognitive deficits in preterm children that is associated with changes in regional brain volumes, cortical thickness, and structural connectivity among cortical and limbic brain regions critical for cognition and emotional well-being.

Miller AP, Baranger DAA, Paul SE, Hatoum AS, Rogers C, Bogdan R, Agrawal A. Characteristics Associated With Cannabis Use Initiation by Late Childhood and Early Adolescence in the Adolescent Brain Cognitive Development (ABCD) Study. JAMA Pediatr. 2023 Jun 26. doi: 10.1001/jamapediatrics.2023.1801. Epub ahead of print. PMID: 37358866.

Weigard A, McCurry KL, Shapiro Z, Martz ME, Angstadt M, Heitzeg MM, Dinov ID, Sripada C. Generalizable prediction of childhood ADHD symptoms from neurocognitive testing and youth characteristics. Transl Psychiatry. 2023 Jun 24;13(1):225. doi: 10.1038/s41398-023-02502-6. PMID: 37355620; PMCID: PMC10290685.

Childhood attention-deficit/hyperactivity disorder (ADHD) symptoms are believed to result from disrupted neurocognitive development. However, evidence for the clinical and predictive value of neurocognitive assessments in this context has been mixed, and there have been no large-scale efforts to quantify their potential for use in generalizable models that predict individuals’ ADHD symptoms in new data. Using data drawn from the Adolescent Brain Cognitive Development Study (ABCD), a consortium that recruited a diverse sample of over 10,000 youth (ages 9-10 at baseline) across 21 U.S. sites, we develop and test cross-validated machine learning models for predicting youths’ ADHD symptoms using neurocognitive abilities, demographics, and child and family characteristics. Models used baseline demographic and biometric measures, geocoded neighborhood data, youth reports of child and family characteristics, and neurocognitive tests to predict parent- and teacher-reported ADHD symptoms at the 1-year and 2-year follow-up time points. Predictive models explained 15-20% of the variance in 1-year ADHD symptoms for ABCD Study sites that were left out of the model-fitting process and 12-13% of the variance in 2-year ADHD symptoms. Models displayed high generalizability across study sites and trivial loss of predictive power when transferred from training data to left-out data. Features from multiple domains contributed meaningfully to prediction, including neurocognition, sex, self-reported impulsivity, parental monitoring, and screen time. This work quantifies the information value of neurocognitive abilities and other child characteristics for predicting ADHD symptoms and provides a foundational method for predicting individual youths’ symptoms in new data across contexts.

Dall’Aglio L, Xu B, Tiemeier H, Muetzel RL. Longitudinal Associations Between White Matter Microstructure and Psychiatric Symptoms in Youth. J Am Acad Child Adolesc Psychiatry. 2023 Jun 23:S0890-8567(23)00322-2. doi: 10.1016/j.jaac.2023.04.019. Epub ahead of print. PMID: 37400062.

Objective: Associations between psychiatric problems and white matter (WM) microstructure have been reported in youth. Yet, a deeper understanding of this relation has been hampered by a dearth of well-powered longitudinal studies and a lack of explicit examination of the bidirectional associations between brain and behavior. We investigated the temporal directionality of WM microstructure and psychiatric symptom associations in youth.

Method: In this observational study, we leveraged the world’s largest single- and multi-site cohorts of neurodevelopment: the Generation R (GenR) and Adolescent Brain Cognitive Development Studies (ABCD) (total n scans = 11,400; total N = 5,700). We assessed psychiatric symptoms with the Child Behavioral Checklist as broad-band internalizing and externalizing scales, and as syndrome scales (eg, Anxious/Depressed). We quantified WM with diffusion tensor imaging (DTI), globally and at a tract level. We used cross-lagged panel models to test bidirectional associations of global and specific measures of psychopathology and WM microstructure, meta-analyzed results across cohorts, and used linear mixed-effects models for validation.

Results: We did not identify any longitudinal associations of global WM microstructure with internalizing or externalizing problems across cohorts (confirmatory analyses) before, and after multiple testing corrections. We observed similar findings for longitudinal associations between tract-based microstructure with internalizing and externalizing symptoms, and for global WM microstructure with specific syndromes (exploratory analyses). Some cross-sectional associations surpassed multiple testing corrections in ABCD, but not in GenR.

Conclusion: Uni- or bi-directionality of longitudinal associations between WM and psychiatric symptoms were not robustly identified. We have proposed several explanations for these findings, including interindividual differences, the use of longitudinal approaches, and smaller effects than expected.

Nagata JM, Alsamman S, Smith N, Yu J, Ganson KT, Dooley EE, Wing D, Baker FC, Pettee Gabriel K. Social epidemiology of Fitbit daily steps in early adolescence. Pediatr Res. 2023 Jun 23. doi: 10.1038/s41390-023-02700-4. Epub ahead of print. PMID: 37353663.

Background: Sociodemographic disparities in adolescent physical activity have been documented but mostly rely on self-reported data. Our objective was to examine differences in device-based step metrics, including daily step count (steps d^-1), by sociodemographic factors among a diverse sample of 10-to-14-year-old adolescents in the US.

Methods: We analyzed prospective cohort data from Year 2 (2018-2020) of the Adolescent Brain Cognitive Development (ABCD) Study (N = 6460). Mixed-effects models were conducted to estimate associations of sociodemographic factors (sex, sexual orientation, race/ethnicity, household income, parental education, and parental marital status) with repeated measures of steps d^-1 over the course of 21 days.

Results: Participants (49.6% female, 39.0% racial/ethnic minority) accumulated an average of 9095.8 steps d^-1. In mixed-effects models, 1543.6 more steps d^-1 were recorded for male versus female sex, Black versus White race (328.8 more steps d^-1), heterosexual versus sexual minority sexual orientation (676.4 more steps d^-1), >$200,000 versus <$25,000 household income (1003.3 more steps d^-1), and having married/partnered parents versus unmarried/unpartnered parents (326.3 more steps d^-1). We found effect modification by household income for Black adolescents and by sex for Asian adolescents.

Conclusions: Given sociodemographic differences in adolescent steps d^-1, physical activity guidelines should focus on key populations and adopt strategies optimized for adolescents from diverse backgrounds.

Impact: Sociodemographic disparities in physical activity have been documented but mostly rely on self-reported data, which can be limited by reporting and prevarication bias. In this demographically diverse sample of 10-14-year-old early adolescents in the U.S., we found notable and nuanced sociodemographic disparities in Fitbit steps per day. More daily steps were recorded for male versus female sex, Black versus White race, heterosexual versus sexual minority, >$100,000 versus <$25,000 household income, and having married/partnered versus unmarried/unpartnered parents. We found effect modification by household income for Black adolescents and by sex for Asian adolescents.

Mariko H, Uban KA. The implications of socioeconomic factors on salivary bioscience methodological variables in a large pediatric multi-site study. Front Public Health. 2023 Jun 22;11:1088043. doi: 10.3389/fpubh.2023.1088043. PMID: 37427258; PMCID: PMC10327643.

Introduction: Salivary bioscience has found increased utilization within pediatric research, given the non-invasive nature of self-collecting saliva for measuring biological markers. With this growth in pediatric utility, more understanding is needed of how social-contextual factors, such as socioeconomic factors or status (SES), influence salivary bioscience in large multi-site studies. Socioeconomic factors have been shown to influence non-salivary analyte levels across childhood and adolescent development. However, less is understood about relationships between these socioeconomic factors and salivary collection methodological variables (e.g., time of saliva collection from waking, time of day of saliva collection, physical activity prior to saliva collection, and caffeine intake prior to saliva collection). Variability in salivary methodological variables between participants may impact the levels of analytes measured in a salivary sample, thus serving as a potential mechanism for non-random systematic biases in analytes.

Methods: Our objective is to examine relationships between socioeconomic factors and salivary bioscience methodological variables within the Adolescent Brain Cognitive Development Study© cohort of children aged 9-10 years old (n = 10,567 participants with saliva samples).

Results: We observed significant associations between household socioeconomic factors (poverty status, education) and salivary collection methodological variables (time since waking, time of day of sampling, physical activity, and caffeine intake). Moreover, lower levels of household poverty and education were significantly associated with more sources of potential bias in salivary collection methodological variables (e.g., longer times since waking, collections later in the day, higher odds of caffeine consumption, and lower odds of physical activity). Consistent associations were not observed with neighborhood socioeconomic factors and salivary methodological variables.

Discussion: Previous literature demonstrates associations between collection methodological variables and measurements of salivary analyte levels, particularly with analytes that are more sensitive to circadian rhythms, pH levels, or rigorous physical activity. Our novel findings suggest that unintended distortions in measured salivary analyte values, potentially resulting from the non-random systematic biases in salivary methodology, need to be intentionally incorporated into analyses and interpretation of results. This is particularly salient for future studies interested in examining underlying mechanisms of childhood socioeconomic health inequities in future analyses.

Raney JH, Al-Shoaibi AA, Ganson KT, Testa A, Jackson DB, Singh G, Sajjad OM, Nagata JM. Associations between adverse childhood experiences and early adolescent problematic screen use in the United States. BMC Public Health. 2023 Jun 22;23(1):1213. doi: 10.1186/s12889-023-16111-x. PMID: 37349707; PMCID: PMC10286460.

Background: Problematic screen use, defined as an inability to control use despite private, social, and professional life consequences, is increasingly common among adolescents and can have significant mental and physical health consequences. Adverse Childhood Experiences (ACEs) are important risk factors in the development of addictive behaviors and may play an important role in the development of problematic screen use.

Methods: Prospective data from the Adolescent Brain Cognitive Development Study (Baseline and Year 2; 2018-2020; N = 9,673, participants who did not use screens were excluded) were analyzed in 2023. Generalized logistic mixed effects models were used to determine associations with ACEs and the presence of problematic use among adolescents who used screens based on cutoff scores. Secondary analyses used generalized linear mixed effects models to determine associations between ACEs and adolescent-reported problematic use scores of video games (Video Game Addiction Questionnaire), social media (Social Media Addiction Questionnaire), and mobile phones (Mobile Phone Involvement Questionnaire). Analyses were adjusted for potential confounders including age, sex, race/ethnicity, highest parent education, household income, adolescent anxiety, depression, and attention-deficit symptoms, study site, and participants who were twins.

Results: The 9,673 screen-using adolescents ages 11-12 years old (mean age 12.0) were racially and ethnically diverse (52.9% White, 17.4% Latino/Hispanic, 19.4% Black, 5.8% Asian, 3.7% Native American, 0.9% Other). Problematic screen use rates among adolescents were identified to be 7.0% (video game), 3.5% (social media), and 21.8% (mobile phone). ACEs were associated with higher problematic video game and mobile phone use in both unadjusted and adjusted models, though problematic social media use was associated with mobile screen use in the unadjusted model only. Adolescents exposed to 4 or more ACEs experienced 3.1 times higher odds of reported problematic video game use and 1.6 times higher odds of problematic mobile phone use compared to peers with no ACEs.

Conclusions: Given the significant associations between adolescent ACE exposure and rates of problematic video and mobile phone screen use among adolescents who use screens, public health programming for trauma-exposed youth should explore video game, social media, and mobile phone use among this population and implement interventions focused on supporting healthy digital habits.

Li R, Lopez DA, Gupta M, Palermo TM. Pubertal development and pain incidence and characteristics in children: a 1-year prospective cohort study of a national sample. Pain. 2023 Jun 21. doi: 10.1097/j.pain.0000000000002969. Epub ahead of print. PMID: 37343155.

Sex differences in pain become apparent during puberty. However, the influence of key pubertal characteristics and pubertal hormones on pain is largely unknown. We examined the prospective associations between self-reported and hormone-indicated pubertal characteristics and pain incidence and severity in 10- to 11-year-old pain-free youth in the Adolescent Brain Cognitive Development (ABCD) Study over 1 year. Puberty was measured at baseline and follow-up with self-report (Pubertal Development Scale [PDS]) and hormonal assessment (salivary dehydroepiandrosterone [DHEA], testosterone, and estradiol). Pain status (yes/no), intensity, and interference (0-10 numerical rating scale) in the past month were self-reported at follow-up. Pubertal maturity, progression, and asynchrony were examined in relation to pain onset and severity through confounder-adjusted generalized estimating equations modified Poisson and linear mixed regression models. Among 6631 pain-free youth at baseline, 1-year incident pain was 30.7%. In both sexes, higher PDS scores were associated with greater risk of pain onset (relative risk [RR] = 1.10 to 1.27, Ps < 0.01). In boys, higher PDS item variance was associated with greater pain incidence (RR = 1.11, 95% CI, 1.03-1.20) and interference (beta = 0.40, 95% CI, 0.03-0.76); higher PDS overall and gonadal scores were associated with higher pain intensity (Ps < 0.05). Associations with hormones were seen in boys only, with each 10-fold higher testosterone levels associated with a 40% lower risk of pain incidence (95% CI, -55% to -22%) and 1.30-point lower (95% CI, -2.12 to -0.48) pain intensity, and higher DHEA levels were associated with lower pain intensity (P = 0.020). Relationships between pubertal development and pain in peripubertal adolescents are sex specific and puberty measurement specific and warrant further investigation.

Makowski C, Brown TT, Zhao W, Hagler DJ, Parekh P, Garavan H, Nichols TE, Jernigan TL, Dale AM. Reports of the death of brain-behavior associations have been greatly exaggerated. bioRxiv [Preprint]. 2023 Jun 16:2023.06.16.545340. doi: 10.1101/2023.06.16.545340. PMID: 37398195; PMCID: PMC10312746.

Magnetic resonance imaging (MRI) has been a popular and useful non-invasive method to map patterns of brain structure and function to complex human traits. Recently published observations in multiple large-scale studies cast doubt upon these prospects, particularly for prediction of cognitive traits from structural and resting state functional MRI, which seems to account for little behavioral variability. We leverage baseline data from thousands of children in the Adolescent Brain Cognitive Development (ABCD) Study to inform the replication sample size required with both univariate and multivariate methods across different imaging modalities to detect reproducible brain-behavior associations. We demonstrate that by applying multivariate methods to high-dimensional brain imaging data, we can capture lower dimensional patterns of structural and functional brain architecture that correlate robustly with cognitive phenotypes and are reproducible with only 42 individuals in the replication sample for working memory-related functional MRI, and ∼100 subjects for structural MRI. Even with 50 subjects in the discovery sample, prediction can be adequately powered with 105 subjects in the replication sample for multivariate prediction of cognition with working memory task functional MRI. These results point to an important role for neuroimaging in translational neurodevelopmental research and showcase how findings in large samples can inform reproducible brain-behavior associations in small sample sizes that are at the heart of many investigators’ research programs and grants.

Brower R. Concussion history is related to performance on executive functioning tasks in youth. Archives of Clinical Neuropsychology, 15 June 2023, acad042.13, https://doi.org/10.1093/arclin/acad042.13

Purpose
Pediatric traumatic brain injuries (TBIs) are among the most common acquired disabilities in youth. They occur when the brain is rapidly developing and therefore many impact the child into adulthood and can impact executive functioning (EF) skills that are vital to everyday tasks, like maintaining attention, organizing, and inhibiting behaviors. It is important to understand the impact of childhood TBIs to learn how to best intervene.

Methods
11,224 children aged 9-10 years old (mean age=9.91, 49.4% male) at baseline completed an extensive battery of interviews and neuropsychological tasks through the Adolescent Brain Cognitive Development (ABCD) study. Based on parent reports on the Ohio State TBI screening measure, children were classified into No/Unlikely TBI, Possible Mild, Mild, Moderate, and Severe TBI. 153 children met criteria for possible mild TBI or higher. They also completed an array of neurocognitive measures, including Matrix Reasoning and several NIH Toolbox executive functioning tasks.

Results
There were small significant correlations between TBI status and a language task (Picture Vocab, r=.03, p=.002), attention task (Flanker, r=.02, p=.04), set shifting (Dimensional Change Card Sort, r=.02, p=.04), and with the crystallized cognition (r=.03, p=.005) and cognition composite (r=.03, p=.005) scores. Trend-level correlations were found for an oral reading task and fluid cognition composite score. However, when children with no TBI history were removed, no correlations held.

Conclusions
A history of even a mild TBI may be related to impaired functioning across several domains of executive functioning skills in youth.

Nagata JM, Yang J, Alsamman S, Al-Shoaibi AAA, Ganson KT, Pettee Gabriel K, Baker FC. Higher blood pressure and weight observed among early adolescents during the COVID-19 pandemic. Am J Prev Cardiol. 2023 Jun;14:100508. doi: 10.1016/j.ajpc.2023.100508. Epub 2023 May 20. PMID: 37313357; PMCID: PMC10198794.

The COVID-19 pandemic led to significant disruptions in the lifestyle behaviors of adolescents; however, there is a paucity of data on objective changes in health indicators of adolescents such as blood pressure, hypertension, and weight. The aim of this study is to quantify differences in blood pressure and weight before and during the COVID-19 pandemic among a demographically diverse national sample of early adolescents. We analyzed cross-sectional data from 2018 to 2020, corresponding to the second follow-up year (Year 2) of the Adolescent Brain Cognitive Development (ABCD) Study. Among 4,065 early adolescents (mean age 12.00, 49.4% female, 55.5% white), 3.4% vs 6.4% of adolescents had hypertension pre-pandemic vs during the pandemic (p < 0.001). The pandemic was associated with a 4.65 percentile (95% CI 2.65, 6.66) higher diastolic blood pressure, and a 1.68 kg (95% CI 0.51, 2.85) higher weight when adjusting for covariates. The pandemic was associated with a 1.97 higher odds of hypertension (95% CI 1.33, 2.92) compared to pre-pandemic when adjusting for covariates. Future studies should explore mechanisms and longitudinal trends in blood pressure among adolescents as they return to pre-pandemic lifestyle behaviors.

Blok E, Lamballais S, Benítez-Manzanas L, White T. The Bidirectional Relationship Between Brain Features and the Dysregulation Profile: A Longitudinal, Multimodal Approach. J Am Acad Child Adolesc Psychiatry. 2023 Jun 14:S0890-8567(23)00309-X. doi: 10.1016/j.jaac.2023.03.024. Epub ahead of print. PMID: 37339753.

Objective: Youth with symptoms of emotion dysregulation are at risk for a multitude of psychiatric diagnoses later in life. However, few studies have focused on the underlying neurobiology of emotion dysregulation. This study assessed the bidirectional relationship between emotion dysregulation symptoms and brain morphology throughout childhood and adolescence.

Method: A combined total of 8,235 children and adolescents drawn from 2 large population-based cohorts, the Generation R Study and Adolescent Brain Cognitive Development (ABCD) Study, were included. Data were acquired in 3 waves in Generation R (mean [SD] age = 7.8 [1.0] wave 1 [W1]; 10.1 [0.6] W2; 13.9 [0.5] W3) and in 2 waves in ABCD (mean [SD] age = 9.9 [0.6] W1; 11.9 [0.6] W2). Cross-lagged panel models were used to determine the bidirectional relationships between emotion dysregulation symptoms and brain morphology. The study was preregistered before performing analyses.

Results: In the Generation R sample, emotion dysregulation symptoms at W1 preceded lower hippocampal (β = -.07, SE = 0.03, p = .017) and temporal pole (β = -.19, SE = 0.07, p = .006) volumes at W2. Emotion dysregulation symptoms at W2 preceded lower fractional anisotropy in the uncinate fasciculus (β = -.11, SE = 0.05, p = .017) and corticospinal tract (β = -.12, SE = 0.05, p = .012). In the ABCD sample, emotion dysregulation symptoms preceded posterior cingulate (β = .01, SE = 0.003, p = .014) and nucleus accumbens volumes (left hemisphere: β = -.02, SE = 0.01, p = .014; right hemisphere: β = -.02, SE = 0.01, p = .003).

Conclusion: In population-based samples, with relatively low psychopathology symptoms in the majority of children, symptoms of emotion dysregulation can precede differential development of brain morphology. This provides the foundation for future work to assess to what extent optimal brain development can be promoted through early intervention.

Study registration information: The Bidirectional Relationship Between Brain Features and the Dysregulation Profile: A Longitudinal, Multimodal Approach; https://doi.org/10.1016/j.jaac.2022.03.008.

Diversity & inclusion statement: We worked to ensure that the study questionnaires were prepared in an inclusive way. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Rodriguez Rivera PJ, Liang H, Isaiah A, Cloak CC, Menken MS, Ryan MC, Ernst T, Chang L. Prenatal tobacco exposure on brain morphometry partially mediated poor cognitive performance in preadolescent children. NeuroImmune Pharm Ther. 2023 Jul 13;2(4):375-386. doi: 10.1515/nipt-2023-0013. PMID: 38058999; PMCID: PMC10696570.

Objectives: To evaluate whether prenatal tobacco exposure (PTE) is related to poorer cognitive performance, abnormal brain morphometry, and whether poor cognitive performance is mediated by PTE-related structural brain differences.

Methods: The Adolescent Brain Cognitive Development study dataset was used to compare structural MRI data and neurocognitive (NIH Toolbox®) scores in 9-to-10-year-old children with (n=620) and without PTE (n=10,989). We also evaluated whether PTE effects on brain morphometry mediated PTE effects on neurocognitive scores. Group effects were evaluated using Linear Mixed Models, covaried for socio-demographics and prenatal exposures to alcohol and/or marijuana, and corrected for multiple comparisons using the false-discovery rate (FDR).

Results: Compared to unexposed children, those with PTE had poorer performance (all p-values <0.05) on executive function, working memory, episodic memory, reading decoding, crystallized intelligence, fluid intelligence and overall cognition. Exposed children also had thinner parahippocampal gyri, smaller surface areas in the posterior-cingulate and pericalcarine cortices; the lingual and inferior parietal gyri, and smaller thalamic volumes (all p-values <0.001). Furthermore, among children with PTE, girls had smaller surface areas in the superior-frontal (interaction-FDR-p=0.01), precuneus (interaction-FDR-p=0.03) and postcentral gyri (interaction-FDR-p=0.02), while boys had smaller putamen volumes (interaction-FDR-p=0.02). Smaller surface areas across regions of the frontal and parietal lobes, and lower thalamic volumes, partially mediated the associations between PTE and poorer neurocognitive scores (p-values <0.001).

Conclusions: Our findings suggest PTE may lead to poorer cognitive performance and abnormal brain morphometry, with sex-specific effects in some brain regions, in pre-adolescent children. The poor cognition in children with PTE may result from the smaller areas and subcortical brain volumes.

He, XY., Wu, BS., Kuo, K. et al. Association between polygenic risk for Alzheimer’s disease and brain structure in children and adults. Alz Res Therapy 15, 109 (2023). https://doi.org/10.1186/s13195-023-01256-z

Background
The correlations between genetic risk for Alzheimer’s disease (AD) with comprehensive brain regions at a regional scale are still not well understood. We aim to explore whether these associations vary across different age stages.

Methods
This study used large existing genome-wide association datasets to calculate polygenic risk score (PRS) for AD in two populations from the UK Biobank (N ~ 23 000) and Adolescent Brain Cognitive Development Study (N ~ 4660) who had multimodal macrostructural and microstructural magnetic resonance imaging (MRI) metrics. We used linear mixed-effect models to assess the strength of the association between AD PRS and multiple MRI metrics of regional brain structures at different stages of life.

Results
Compared to those with lower PRSs, adolescents with higher PRSs had thinner cortex in the caudal anterior cingulate and supramarginal. In the middle-aged and elderly population, AD PRS had correlations with regional structure shrink primarily located in the cingulate, prefrontal cortex, hippocampus, thalamus, amygdala, and striatum, whereas the brain expansion was concentrated near the occipital lobe. Furthermore, both adults and adolescents with higher PRSs exhibited widespread white matter microstructural changes, indicated by decreased fractional anisotropy (FA) or increased mean diffusivity (MD).

Conclusions
In conclusion, our results suggest genetic loading for AD may influence brain structures in a highly dynamic manner, with dramatically different patterns at different ages. This age-specific change is consistent with the classical pattern of brain impairment observed in AD patients.

Owens MM, Hyatt CS, Xu H, Thompson MF, Miller JD, Lynam DR, MacKillop J, Gray JC. Test-retest reliability of the neuroanatomical correlates of impulsive personality traits in the adolescent brain cognitive development study. J Psychopathol Clin Sci. 2023 Jun 12. doi: 10.1037/abn0000832. Epub ahead of print. PMID: 37307315.

While the neuroanatomical correlates of impulsivity in youths have been examined, there is little research on whether those correlates are consistent across childhood/adolescence. The current study uses data from the age 11/12 (N = 7,083) visit of the Adolescent Brain Cognitive Development Study to investigate the replicability of previous work (Owens et al., 2020) the neuroanatomical correlates of impulsive personality traits identified at age 9/10. Neuroanatomy was measured using structural and diffusion magnetic resonance imaging, and impulsive personality was measured using the UPPS-P Impulsive Behavior Scale. Replicability was quantified using three Open Science Collaboration replication criteria, intraclass correlations, and elastic net regression modeling to make predictions across timepoints. Replicability was highly variable among traits: The neuroanatomical correlates of positive urgency showed substantial similarity between ages 9/10 and 11/12, negative urgency and sensation seeking showed moderate similarity across ages, and (lack of) premeditation and perseverance showed substantial dissimilarity across ages. In all cases, effect sizes between impulsive traits and brain variables were small. These findings suggest that, even for studies with large sample sizes and the same participant pool, the replicability of brain-behavior correlations across a 2-year period cannot be assumed. This may be due to developmental changes across the two timepoints or false-positive/false-negative results at one or both timepoints. These results also highlight an array of neuroanatomical structures that may be important to impulsive personality traits across development from childhood into adolescence.

Nath N, Beltrano W, Haynes L, Dewey D, Bray S. Long-Term Effects of Preterm Birth on Children’s Brain Structure: An Analysis of the Adolescent Brain Cognitive Development (ABCD) Study. eNeuro. 2023 Jun 9;10(6):ENEURO.0196-22.2023. doi: 10.1523/ENEURO.0196-22.2023. PMID: 37277147; PMCID: PMC10262676.

Beck D, Ferschmann L, MacSweeney N, Norbom LB, Wiker T, Aksnes E, Karl V, Dégeilh F, Holm M, Mills KL, Andreassen OA, Agartz I, Westlye LT, von Soest T, Tamnes CK. Puberty differentially predicts brain maturation in male and female youth: A longitudinal ABCD Study. Dev Cogn Neurosci. 2023 Jun 7;61:101261. doi: 10.1016/j.dcn.2023.101261. Epub ahead of print. PMID: 37295068.

Research has demonstrated associations between pubertal development and brain maturation. However, existing studies have been limited by small samples, cross-sectional designs, and inconclusive findings regarding directionality of effects and sex differences. We examined the longitudinal temporal coupling of puberty status assessed using the Pubertal Development Scale (PDS) and magnetic resonance imaging (MRI)-based grey and white matter brain structure. Our sample consisted of 8896 children and adolescents at baseline (mean age = 9.9) and 6099 at follow-up (mean age = 11.9) from the Adolescent Brain and Cognitive Development (ABCD) Study cohort. Applying multigroup Bivariate Latent Change Score (BLCS) models, we found that baseline PDS predicted the rate of change in cortical thickness among females and rate of change in cortical surface area for both males and females. We also found a correlation between baseline PDS and surface area and co-occurring changes over time in males. Diffusion tensor imaging (DTI) analyses revealed correlated change between PDS and fractional anisotropy (FA) for both males and females, but no significant associations for mean diffusivity (MD). Our results suggest that pubertal status predicts cortical maturation, and that the strength of the associations differ between sex. Further research spanning the entire duration of puberty is needed to understand the extent and contribution of pubertal development on the youth brain.

Norman LJ, Price J, Ahn K, Sudre G, Sharp W, Shaw P. Longitudinal trajectories of childhood and adolescent attention deficit hyperactivity disorder diagnoses in three cohorts. EClinicalMedicine. 2023 Jun 6;60:102021. doi: 10.1016/j.eclinm.2023.102021. PMID: 37333663; PMCID: PMC10272308.

Background: Attention deficit/hyperactivity disorder (ADHD) is usually conceptualized as a childhood-onset neurodevelopmental disorder, in which symptoms either decrease steadily into adulthood or remain stable. A recent study challenged this view, reporting that for most with ADHD, diagnostic status fluctuates with age. We ask if such a ‘fluctuating’ ADHD symptom trajectory subgroup is present in other population-based and clinic-based cohorts, centered on childhood and adolescence.

Methods: Cohorts were the population-based Adolescent Brain Cognitive Development (ABCD: N = 9735), Neurobehavioral Clinical Research (NCR: N = 258), and the Nathan Kline Institute-Rockland (NKI-Rockland: N = 149). All participants had three or more assessments spanning different age windows. Participants were categorized into developmental diagnostic subgroups: fluctuant ADHD (defined by two or more switches between meeting and not meeting ADHD criteria), remitting ADHD, persisting ADHD, emerging ADHD and never affected. Data were collected between 2011 and 2022. Analyses were performed between May 2022 and April 2023.

Findings: A subgroup with fluctuant child and adolescent ADHD diagnoses was found in all cohorts (29.3% of participants with ADHD in ABCD, 26.6% in NCR and 17% in NKI-Rockland). While the proportion of those with fluctuant ADHD increased with the number of assessments, it never constituted the dominant subgroup.

Interpretation: We provide further evidence in three cohorts for the existence of a fluctuant ADHD diagnostic subgroup during childhood and adolescence, albeit in a minority of cases. Such fluctuant child and adolescent ADHD diagnoses may suggest a natural history more akin to relapsing-remitting mood disorders and/or a marked sensitivity to environmental shifts that occur across development.

Elam KK, Su J, Aliev F, Trevino A, Kutzner J, Seo DC. Polygenic Effects on Individual Rule Breaking, Peer Rule Breaking, and Alcohol Sips Across Early Adolescence in the ABCD Study. Res Child Adolesc Psychopathol. 2023 Jun 5. doi: 10.1007/s10802-023-01090-9. Epub ahead of print. PMID: 37273065.

Alcohol use emerges during early adolescence and is strongly associated with individual and peer risky, delinquent, and rule breaking behaviors. Genetic predisposition for risky behavior contributes to individual rule breaking in adolescence and can also evoke peer rule breaking or lead youth to select into delinquent peer groups via gene-environment correlations (rGE), collectively increasing risk for alcohol use. Little research has examined whether genetic predisposition for risky behavior contributes to individual and peer rule breaking behavior in developmental pathways to alcohol use in early adolescence or in large diverse racial/ethnic populations. To address this, polygenic scores for risky behavior were considered predictors of individual rule breaking, peer rule breaking, and alcohol sips using data from the Adolescent Brain Cognitive Development (ABCD) study at age 11-12 and 12-13 in a cross-time cross-lagged model. This was examined separately in European American (EA; n = 5113; 47% female), African American (AA; n = 1159; 50% female), and Hispanic/Latinx (Latinx; n = 1624; 48% female) subgroups accounting for sociodemographic covariates and genetic ancestry principal components. Polygenic scores were positively associated with all constructs in EAs, with individual rule breaking at age 11-12 in AAs and Latinx, and with alcohol sips at age 11-12 in Latinx. Individual and peer rule breaking were associated with one another across time only in the EA subgroup. In all subgroups, peer rule breaking at 12-13 was associated with alcohol sips at 12-13. Results indicate that alcohol sips in early adolescence are associated with individual and peer rule breaking with rGE implicated in EAs.

Vedechkina M, Bennett M, Holmes J. Dimensions of internalizing symptoms are stable across early adolescence and predicted by executive functions: Longitudinal findings from the Adolescent Brain and Cognitive Development (ABCD) study. Dev Psychopathol. 2023 Jun 5:1-10. doi: 10.1017/S0954579423000524. Epub ahead of print. PMID: 37272416.

Early adolescence is characterized by rapid changes in executive function and increased vulnerability to internalizing difficulties. The aim of this study was to explore whether internalizing symptoms are stable across early adolescence and to identify possible links with executive function. Using data from the Adolescent Brain and Cognitive Development Study (ABCD), we identified four dimensions of internalizing symptoms from item-level ratings on the Child Behavior Checklist at ages 10 (n = 10,841) and 12 (n = 5,846), with an invariant factor structure across time. These dimensions corresponded to anxiety, depression, withdrawal, and somatic problems. We then examined associations between these dimensions and three aspects of executive function at age 10 measured by the NIH Toolbox: inhibition, shifting and working memory. Worse shifting and inhibition at age 10 was associated with elevated symptoms of anxiety and withdrawal cross-sectionally, while poor inhibition was also uniquely associated with symptoms of depression. Longitudinal associations were more limited: Worse inhibition at age 10 predicted greater symptoms of withdrawal at age 12, while worse shifting predicted fewer symptoms of anxiety 2 years later. These findings suggest that poor executive function in early adolescence is associated with greater internalizing difficulties and poor inhibition may contribute to later social withdrawal.

Roberts C, Sahakian BJ, Chen S, Sallie SN, Walker C, White SR, Weber J, Skandali N, Robbins TW, Murray GK. Impact and centrality of attention dysregulation on cognition, anxiety, and low mood in adolescents. Sci Rep. 2023 Jun 5;13(1):9106. doi: 10.1038/s41598-023-34399-y. PMID: 37277504; PMCID: PMC10241800.

Functional impairments in cognition are frequently thought to be a feature of individuals with depression or anxiety. However, documented impairments are both broad and inconsistent, with little known about when they emerge, whether they are causes or effects of affective symptoms, or whether specific cognitive systems are implicated. Here, we show, in the adolescent ABCD cohort (N = 11,876), that attention dysregulation is a robust factor underlying wide-ranging cognitive task impairments seen in adolescents with moderate to severe anxiety or low mood. We stratified individuals high in DSM-oriented depression or anxiety symptomology, and low in attention deficit hyperactivity disorder (ADHD), as well as vice versa – demonstrating that those high in depression or anxiety dimensions but low in ADHD symptoms not only exhibited normal task performance across several commonly studied cognitive paradigms, but out-performed controls in several domains, as well as in those low in both dimensions. Similarly, we showed that there were no associations between psychopathological dimensions and performance on an extensive cognitive battery after controlling for attention dysregulation. Further, corroborating previous research, the co-occurrence of attention dysregulation was associated with a wide range of other adverse outcomes, psychopathological features, and executive functioning (EF) impairments. To assess how attention dysregulation relates to and generates diverse psychopathology, we performed confirmatory and exploratory network analysis with different analytic approaches using Gaussian Graphical Models and Directed Acyclic Graphs to examine interactions between ADHD, anxiety, low mood, oppositional defiant disorder (ODD), social relationships, and cognition. Confirmatory centrality analysis indicated that features of attention dysregulation were indeed central and robustly connected to a wide range of psychopathological traits across different categories, scales, and time points. Exploratory network analysis indicated potentially important bridging traits and socioenvironmental influences in the relationships between ADHD symptoms and mood/anxiety disorders. Trait perfectionism was uniquely associated with both better cognitive performance and broad psychopathological dimensions. This work suggests that attentional dysregulation may moderate the breadth of EF, fluid, and crystalized cognitive task outcomes seen in adolescents with anxiety and low mood, and may be central to disparate pathological features, and thus a target for attenuating wide-ranging negative developmental outcomes.

Vijayakumar N, Whittle S, Silk TJ. Corticolimbic connectivity mediates the relationship between pubertal timing and mental health problems. Psychol Med. 2023 Jun 2:1-11. doi: 10.1017/S0033291723001472. Epub ahead of print. PMID: 37264939.

Background: Undergoing puberty ahead of peers (‘earlier pubertal timing’) is an important risk factor for mental health problems during early adolescence. The current study examined pathways between pubertal timing and mental health via connectivity of neural systems implicated in emotional reactivity and regulation (specifically corticolimbic connections) in 9- to 14-year-olds.

Method: Research questions were examined in the Adolescent Brain Cognitive Development (ABCD) Study, a large population representative sample in the United States. Linear mixed models examined associations between pubertal timing and resting-state corticolimbic connectivity. Significant connections were examined as potential mediators of the relationship between pubertal timing and mental health (withdrawn depressed and rule-breaking) problems. Exploratory analyses interrogated whether the family environment moderated neural risk patterns in those undergoing puberty earlier than their peers.

Results: Earlier pubertal timing was related to decreased connectivity between limbic structures (bilateral amygdala and right hippocampus) and the cingulo-opercular network, left amygdala and somatomotor (mouth) network, as well as between the left hippocampus and ventral attention network and visual network. Corticolimbic connections also mediated the relationship between earlier pubertal timing and increased withdrawn depressed problems (but not rule-breaking problems). Finally, parental acceptance buffered against connectivity patterns that were implicated in withdrawn depressed problems in those undergoing puberty earlier than their peers.

Conclusion: Findings highlight the role of decreased corticolimbic connectivity in mediating pathways between earlier pubertal timing and withdrawn depressed problems, and we present preliminary evidence that the family environment may buffer against these neural risk patterns during early adolescence.

Freeman C, Olino T, Barbeau EB, Weinberg A, Chai X. Family History of Depression and Neural Reward Sensitivity: Findings From the Adolescent Brain Cognitive Development Study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2023 Jun;8(6):620-629. doi: 10.1016/j.bpsc.2022.09.015. Epub 2022 Oct 13. PMID: 36797123.

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

Methods: Data from the baseline visit of the ABCD (Adolescent Brain Cognitive Development) Study were used. After exclusion criteria, 7233 9- and 10-year-old children (49% female) were included in analyses. Neural responses to reward anticipation and receipt in the monetary incentive delay task were examined in 6 striatal regions of interest. Using mixed-effects models, we evaluated the effect of maternal or paternal depression history on striatal reward response. We also evaluated the effect of family history density on reward response.

Results: Across all 6 striatal regions of interest, neither maternal nor paternal depression significantly predicted blunted response to reward anticipation or feedback. Contrary to hypotheses, paternal depression history was associated with increased response in the left caudate during anticipation, and maternal depression history was associated with increased response in the left putamen during feedback. Family history density was not associated with striatal reward response.

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

Sheth C, Huber RS, Renshaw PF, Yurgelun-Todd DA, McGlade EC. Mild Traumatic Brain Injury and Behavior and Sleep Among 9- and 10-Year Old Children: Initial Findings From the Adolescent Brain Cognitive Development (ABCD) Study. J Early Adolesc. 2023 Jun;43(6):720-745. doi: 10.1177/02724316221117508. Epub 2022 Nov 14. PMID: 37780352; PMCID: PMC10540300.

There has been concern about the potential sequelae of mild traumatic brain injury (mTBI) in children. This study used data from the Adolescent Brain Cognitive DevelopmentSM (ABCD) study to investigate associations between mTBI and behavior and sleep in school-aged children. Generalized additive mixed models were run to examine the association between TBI and parent-reported Child Behavior Checklist and Sleep Disturbance Scale for Children scores. mTBI with or without loss of consciousness (LOC) in 9- and 10-year old children was associated with 1) higher internalizing, externalizing and total problems and 2) greater sleep disturbance scores on the CBCL. The study also demonstrated a higher incidence of mTBI with and without LOC in boys compared to girls. This study shows a statistically significant but modest association between mTBI and behavioral and sleep changes, suggesting that in a non-clinical, sociodemographically diverse community sample of school-aged children mTBI does not result in clinically significant behavioral or psychological sequelae.

Duffy KA, Gandhi R, Falke C, Wiglesworth A, Mueller BA, Fiecas MB, Klimes-Dougan B, Luciana M, Cullen KR. (In Press, 2023). Psychiatric Diagnoses and Treatment in Nine- to Ten-Year-Old Participants in the ABCD Study. JAACAP Open. Volume 1, Issue 1, June 2023, Pages 36-47. https://doi.org/10.1016/j.jaacop.2023.03.001

Objective
Psychiatric disorders commonly emerge before adulthood. Identification and intervention may vary significantly across populations. A large population-based study was leveraged to estimate the prevalence of psychiatric disorders and treatments and evaluate predictors of treatment in children ages 9 and 10 in the United States.

Method
Cross-sectional data from the Adolescent Brain Cognitive Developmental (ABCD) Study were analyzed. The Schedule for Affective Disorders and Schizophrenia for School-Age Children–Computerized version (K-SADS-COMP) was used to estimate clinical diagnoses, and the Child Behavior Checklist (CBCL) was used to assess internalizing and externalizing psychopathology. Parents reported on prescription medications and other mental health interventions. Prevalence rates of K-SADS diagnoses and treatments were calculated. Logistic regression analyses estimated associations between clinical and sociodemographic predictors (sex at birth, race, ethnicity, income, education, urbanicity) and treatments.

Results
The most common K-SADS diagnoses were anxiety disorders, followed by attention-deficit/hyperactivity disorder, and oppositional defiant disorder. Attention-deficit/hyperactivity disorder and depression diagnoses predicted stimulant and antidepressant medication use, respectively. Bipolar and attention-deficit/hyperactivity disorder diagnoses also predicted antidepressant medications, outpatient treatment, and psychotherapy. The odds of reporting specific treatments varied by sex, ethnic and racial identities, urbanicity, and income.

Conclusion
Expected rates of K-SADS-based psychiatric symptoms are present in the ABCD sample at ages 9 and 10, with treatment patterns broadly mapping onto psychopathology in expected ways. However, important variations in reported treatment utilization across sociodemographic groups were observed, likely reflecting societal and cultural influences. Findings are considered in the context of potential mental health disparities in US children.

Li ZA, Cai Y, Taylor RL, Eisenstein SA, Barch DM, Marek S, Hershey T. Associations Between Socioeconomic Status, Obesity, Cognition, and White Matter Microstructure in Children. JAMA Netw Open. 2023 Jun 1;6(6):e2320276. doi: 10.1001/jamanetworkopen.2023.20276. PMID: 37368403.

Importance: Lower neighborhood and household socioeconomic status (SES) are associated with negative health outcomes and altered brain structure in children. It is unclear whether such findings extend to white matter and via what mechanisms.

Objective: To assess whether and how neighborhood and household SES are independently associated with children’s white matter microstructure and examine whether obesity and cognitive performance (reflecting environmental cognitive and sensory stimulation) are plausible mediators.

Design, setting, and participants: This cross-sectional study used baseline data from participants in the Adolescent Brain Cognitive Development (ABCD) study. Data were collected at 21 US sites, and school-based recruitment was used to represent the US population. Children aged 9 to 11 years and their parents or caregivers completed assessments between October 1, 2016, and October 31, 2018. After exclusions, 8842 of 11 875 children in the ABCD study were included in the analyses. Data analysis was conducted from July 11 to December 19, 2022.

Exposures: Neighborhood disadvantage was derived from area deprivation indices at participants’ primary residence. Household SES factors were total income and highest parental educational attainment.

Main outcomes and measures: A restriction spectrum imaging (RSI) model was used to quantify restricted normalized directional (RND; reflecting oriented myelin organization) and restricted normalized isotropic (RNI; reflecting glial and neuronal cell bodies) diffusion in 31 major white matter tracts. The RSI measurements were scanner harmonized. Obesity was assessed through body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), age- and sex-adjusted BMI z scores, and waist circumference, and cognition was assessed through the National Institutes of Health Toolbox Cognition Battery. Analyses were adjusted for age, sex, pubertal development stage, intracranial volume, mean head motion, and twin or siblingship.

Results: Among 8842 children, 4543 (51.4%) were boys, and the mean (SD) age was 9.9 (0.7) years. Linear mixed-effects models revealed that greater neighborhood disadvantage was associated with lower RSI-RND in the left superior longitudinal fasciculus (β = -0.055; 95% CI, -0.081 to -0.028) and forceps major (β = -0.040; 95% CI, -0.067 to -0.013). Lower parental educational attainment was associated with lower RSI-RND in the bilateral superior longitudinal fasciculus (eg, right hemisphere: β = 0.053; 95% CI, 0.025-0.080) and bilateral corticospinal or pyramidal tract (eg, right hemisphere: β = 0.042; 95% CI, 0.015-0.069). Structural equation models revealed that lower cognitive performance (eg, lower total cognition score and higher neighborhood disadvantage: β = -0.012; 95% CI, -0.016 to -0.009) and greater obesity (eg, higher BMI and higher neighborhood disadvantage: β = -0.004; 95% CI, -0.006 to -0.001) partially accounted for the associations between SES and RSI-RND. Lower household income was associated with higher RSI-RNI in most tracts (eg, right inferior longitudinal fasciculus: β = -0.042 [95% CI, -0.073 to -0.012]; right anterior thalamic radiations: β = -0.045 [95% CI, -0.075 to -0.014]), and greater neighborhood disadvantage had similar associations in primarily frontolimbic tracts (eg, right fornix: β = 0.046 [95% CI, 0.019-0.074]; right anterior thalamic radiations: β = 0.045 [95% CI, 0.018-0.072]). Lower parental educational attainment was associated with higher RSI-RNI in the forceps major (β = -0.048; 95% CI, -0.077 to -0.020). Greater obesity partially accounted for these SES associations with RSI-RNI (eg, higher BMI and higher neighborhood disadvantage: β = 0.015; 95% CI, 0.011-0.020). Findings were robust in sensitivity analyses and were corroborated using diffusion tensor imaging.

Conclusions and relevance: In this cross-sectional study, both neighborhood and household contexts were associated with white matter development in children, and findings suggested that obesity and cognitive performance were possible mediators in these associations. Future research on children’s brain health may benefit from considering these factors from multiple socioeconomic perspectives.

Zhang L, Kiss O, Nagata J, de Zambotti M, Baker FC, Oshri A.. Sleep Duration Moderates The Link Between Youth Impulsivity And Mature-Rated Media Usage One Year Later. Sleep, Volume 46, Issue Supplement_1, May 2023, Pages A94–A95, https://doi.org/10.1093/sleep/zsad077.0214

Introduction
Adolescents who evince higher levels of impulsive traits are more susceptible to early use of mature-rated gaming and watching R-rated movies. This is a major public health concern because exposure to mature-rated media in youth is associated with decreased empathy and aggressive behaviors later in life. However, not all youth with higher impulsive traits will be engaged in those risky media activities. Sleep is a critical bioregulatory behavior during adolescence, and shorter sleep duration is associated with decreased emotional regulation and attention span. Yet, few studies examined whether sleep duration moderates the association between impulsivity and risky media usage.

Methods
The current study examines the associations between sleep, impulsivity, and mature-rated video gaming and movie watching using longitudinal data of 2,757 early adolescents (49.3% female, Mage at 3-year follow-up=12.9 years, SD=0.65), collected through the Adolescent Brain Cognitive Development Study® (2021, release 4.0). The participants’ weighted weekly sleep duration was measured via Fitbit watches for at least seven days at 2-year follow-up. Participants completed questionnaires about impulsivity via UPPS-P Impulsive Behavior Scale at 2-year follow-up and R-rated movie watching and mature video gaming at 2- and 3-year follow-up. Structural equation modeling was conducted in Mplus 8.1 to test impulsivity and sleep duration’s direct and interaction effects on mature media use while controlling for bedtime screen use, parental monitoring, and demographic covariates.

Results
Higher impulsivity was predictive for more R-rated movie watching (β=0.09, p<.001) one year later. Shorter sleep duration was predictive for more mature video gaming (β=-0.05, p=.006) and R-rated movie watching (β=-0.07, p<.001) one year later. Sleep duration moderates the association between impulsivity and R-rated movie watching (β=-0.04, p=.03). Among youth with high impulsivity, shorter sleep duration was associated with an increased risk for R-rated movie watching.

Conclusion
Impulsivity is associated with R-rated movie watching, and short sleep duration (objectively measured with Fitbit) in early adolescence partially moderates the association between impulsivity and mature media usage. Sleep duration may be a modifiable factor for prevention and intervention efforts, especially in adolescents at higher risk for excessive mature-rated media usage.

Yang FN, Liu TT, Wang Z. Corticostriatal connectivity mediates the reciprocal relationship between parent-reported sleep duration and impulsivity in early adolescents. J Child Psychol Psychiatry. 2023 May 29. doi: 10.1111/jcpp.13843. Epub ahead of print. PMID: 37248201.

Background: Adolescence, a developmental period characterized by significant changes in sleep, is associated with normative increases in impulsivity. While short sleep duration has been linked to elevated impulsivity, the neural mechanism underlying the relationship between short sleep duration and elevated impulsivity remains poorly understood.

Methods: We analyzed a dataset of 7,884 drug-naive 9-10 year-olds from the Adolescent Brain Cognitive Development (ABCD) study. Among them, 5,166 have two-year follow-up neuroimaging data. Linear mixed-effects models, mediation analyses, and longitudinal mediation analyses were used to investigate the relationship between parent-reported sleep duration, impulsivity, and functional and structural connectivity between the cortex and the striatum.

Results: We found that less sleep duration is significantly associated with higher positive and negative urgency, which are two affect-related components of impulsivity. In addition, we observed a link between short sleep duration and reduced corticostriatal connectivity. Neural pathways associated with short sleep duration-functional connectivity between the cingulo-opercular network and the left caudate, and between the cingulo-parietal network and the right pallidum-mediated the association between sleep duration and positive urgency both at baseline and two-year follow-up. Longitudinal mediation analyses further revealed that short sleep duration and elevated positive urgency exacerbated each other through these two corticostriatal connectivities.

Conclusions: These findings highlight the key role of corticostriatal connectivities in the reciprocal relationship between short sleep duration and elevated impulsivity. Given the increasing prevalence of short sleep duration in adolescents, the link between sleep duration, impulsivity, and corticostriatal connectivities has important implications for timely interventions to address impulsive problems in early adolescents.

Orsolya Kiss and others, 0752 Later chronotype, insufficient and disturbed sleep are linked to menstruation problems in early adolescent girls, Sleep, Volume 46, Issue Supplement_1, May 2023, Page A332, https://doi.org/10.1093/sleep/zsad077.0752

Introduction
Adolescence in girls is a vulnerable transitional period, characterized by substantial hormonal and physical development, the onset of menarche, dramatic brain development and changes in behavior, including sleep. Menstrual problems, including painful menses, are common among female adolescents, and contribute to school absenteeism. They may also be symptoms of gynecological conditions, which can negatively affect reproductive and general health of women. Limited work has linked sleep disturbances and menstrual problems in adolescents. Here, we examined the association between sleep behavior and menstrual problems in a large sample of adolescent girls in the Adolescent Brain Cognitive Development (ABCD) Study®.

Methods
We fitted linear mixed effect models to examine the associations between sleep behavior and menstrual problems in 1837 post-menarcheal girls (Year 3, Mean-age = 13.03, [12-15] years), assessed as part of the ongoing ABCD Study®. Sleep was assessed with the Munich Chronotype questionnaire (youth-report) and the sleep disturbance scale for children (caregiver-report). Girls answered questions about menstrual cycles and associated problems. We considered age, time since menarche, BMI, use of hormonal contraceptives, and socio-demographic characteristics in the models.

Results
Short sleep duration was related to higher menstrual pain intensity (p<.01), irregular menstrual cycles (p<.01) and more premenstrual symptoms (p=.01). Higher total sleep disturbance score (caregiver-reported) was also associated with higher menstrual pain intensity (p<.01) and greater impact of menstrual pain on usual activities (p<.01). Participants with a later chronotype (p=.04) and later wake-up time (p=.02) were more likely to experience an irregular menstrual cycle. Later wake-up time was also related to higher menstrual pain intensity and impact on daily life (p<.01). Girls with recent menarche reported heavier menstrual flow (p=.02), higher menstrual pain intensity, more premenstrual symptoms, and a greater overall impact of menstrual pain on their usual activities (p<.01).

Conclusion
Our results indicate multiple associations between sleep behavior and menstrual problems in adolescent girls. Both menstrual problems and insufficient sleep/sleep disturbances are important for female adolescent health and should be routinely screened for by healthcare providers and school health education providers. Future work is needed with longitudinal analyses to determine directionality of the associations we found between sleep and menstrual problems.

Muliyil S. Untangling the links between economics and youth mental health. Nature Medicine (Research Highlight), 26 May 2023.

Emerging evidence suggests an association between family income and structural differences in the developing brain. However, there has been a dearth of well-designed cross-sectional studies spanning different communities that could validate this association.

Weissman et al. analyzed data from the Adolescent Brain Cognitive Development (ABCD) study comprising 10,000 adolescents, 9–11 years of age, from 17 US states that differ in their cost of living and anti-poverty policies. Lower family income was generally associated with a higher incidence of mental health problems and smaller hippocampal volume in these adolescents. However, disparities between adolescents from high-income households and those from low-income households in terms of brain structure and mental health symptoms were much lower in states with anti-poverty policies.

These findings have implications for research in psychology and cognitive neuroscience, where the broader context is often ignored in comparisons of results from different communities, which can lead to potential replication failure. At the same, it is also important to further validate such findings through longitudinal studies involving children of other age groups, potentially spanning a larger number of states in the United States and beyond, to strengthen the associations uncovered.

Ou YN, Ge YJ, Wu BS, Zhang Y, Jiang YC, Kuo K, Yang L, Tan L, Feng JF, Cheng W, Yu JT. The genetic architecture of fornix white matter microstructure and their involvement in neuropsychiatric disorders. Transl Psychiatry. 2023 May 26;13(1):180. doi: 10.1038/s41398-023-02475-6. PMID: 37236919; PMCID: PMC10220072.

The fornix is a white matter bundle located in the center of the hippocampaldiencephalic limbic circuit that controls memory and executive functions, yet its genetic architectures and involvement in brain disorders remain largely unknown. We carried out a genome-wide association analysis of 30,832 UK Biobank individuals of the six fornix diffusion magnetic resonance imaging (dMRI) traits. The post-GWAS analysis allowed us to identify causal genetic variants in phenotypes at the single nucleotide polymorphisms (SNP), locus, and gene levels, as well as genetic overlap with brain health-related traits. We further generalized our GWAS in adolescent brain cognitive development (ABCD) cohort. The GWAS identified 63 independent significant variants within 20 genomic loci associated (P < 8.33 × 10-9) with the six fornix dMRI traits. Geminin coiled-coil domain containing (GMNC) and NUAK family SNF1-like kinase 1 (NUAK1) gene were highlighted, which were found in UKB and replicated in ABCD. The heritability of the six traits ranged from 10% to 27%. Gene mapping strategies identified 213 genes, where 11 were supported by all of four methods. Gene-based analyses revealed pathways relating to cell development and differentiation, with astrocytes found to be significantly enriched. Pleiotropy analyses with eight neurological and psychiatric disorders revealed shared variants, especially with schizophrenia under the conjFDR threshold of 0.05. These findings advance our understanding of the complex genetic architectures of fornix and their relevance in neurological and psychiatric disorders.

Sanchez M, Gonzalez MR, Fernandez A, Barton A, Diaz V, Wang W. Sociocultural influences on alcohol expectancies in early adolescence: Findings from the ABCD study. Health Psychol. 2023 May 25. doi: 10.1037/hea0001290. Epub ahead of print. PMID: 37227824.

Objective: Alcohol expectancies (AE) during early adolescence predict early alcohol use initiation and problem drinking both cross-sectionally and prospectively well into adulthood. Yet, our understanding of the sociocultural factors associated with AE during this development period remains limited. This study examines associations between AE and sociocultural factors across various domains (i.e., individual, family, peer, school, community, and culture) in a demographically diverse sample of 10- to 14-year-old youth in the Adolescent Brain Cognitive Development Study (ABCD Study).

Method: This cross-sectional study used 2-year follow-up data from the ABCD Release 3.0 for N = 5,322 early adolescents (Mage = 12 years [SD = 0.6]; 47% male). Approximately 60% identified as non-Hispanic/Latinx White, 17% as Hispanic/Latinx, 11% as non-Hispanic/Latinx Black, 2% as non-Hispanic/Latinx Asian, and 11% as mixed/other race-ethnicity. Separate models for positive and negative AE outcomes were conducted using linear mixed-effect models while controlling for demographic covariates.

Results: Positive AE were most strongly associated with familism, followed by other peer, school, community, and cultural level factors. Negative AE were most strongly associated with the peer-level factor of relational victimization and the individual-level factor of negative life events, followed by other peer, school, and community-level factors.

Conclusion: The present findings reveal the potential constellation of sociocultural factors that may serve as targets for modifying AE during the middle school years. Study results also underscore the need for future research that integrates cultural factors into our understanding of alcohol use risk and resilience during early adolescence.

Teeuw J, Mota NR, Klein M, Blankenstein NE, Tielbeek JJ, Jansen LMC, Franke B, Pol HEH. Polygenic risk scores and brain structures both contribute to externalizing behavior in childhood A study in the Adolescent Brain and Cognitive Development (ABCD) cohort. Neuroscience Applied. Volume 2, 2023, 101128. https://doi.org/10.1016/j.nsa.2023.101128

Introduction
Externalizing behaviors are defined as behaviors violating social norms and can be harmful to self and others. Predicting the escalation of externalizing behaviors in children would allow for early interventions to prevent the occurrence of antisocial and criminal acts. Externalizing behaviors are heritable traits, and have been associated with structures of the brain. Brain structure, in turn, is also influenced by genetics. Here, we investigated the association of genetic and brain structural variation with externalizing behaviors in late childhood, and we assessed potential mediating effects.

Methods
Data was collected for 11,878 children aged 9–10 years old from the Adolescent Brain Cognitive Development (ABCD) cohort. We extracted data on externalizing behaviors measured by the parent-reported Child Behavior Checklist (CBCL), brain volumes and white matter integrity measured by magnetic resonance imaging (MRI), and polygenic risk scores (PRS) for (i) antisocial behaviors, (ii) attention-deficit/hyperactivity disorder comorbid with disruptive behavior disorder (ADHD + DBD), (iii) irritability, and (iv) traits related to self-regulation & addiction. We examined the associations between brain structures, PRS, and externalizing behavior, and to what extent brain structures mediate the association between PRS and externalizing behavior. Phenotypic associations between brain structures and externalizing behaviors were validated in an independent cohort of 150 adolescents aged 12–21 years enriched for individuals with antisocial behavior.

Results
Increasing levels of externalizing behaviors were associated with reduced total brain and focal gray matter volumes, but not with white matter integrity. These results could not be validated in the independent cohort, except for a good correlation of several effect sizes between the cohorts. Higher PRS for externalizing behaviors were associated with lower cortical gray matter volume, larger subcortical gray matter volume, larger white matter volume, and reduced global white matter fractional anisotropy. Genetic and brain structural variation, combined with sociodemographic factors, explained up to 7% of variation in externalizing behaviors in late childhood; brain structures and PRS each explained up to ∼0.5% of variation. A multivariate model with all sociodemographic factors, brain structures and PRS combined explained up to 11.9% (+5%). Total cortical gray matter volume mediated the association between PRS for ADHD + DBD and externalizing behavior in late childhood. However, a large proportion of individual variation in externalizing behavior remained unidentified (∼90%). Brain function and interaction effects with the environment are surmised as potential sources of additional variation.

Hullenaar KL, Rowhani-Rahbar A, Morgan ER, Hicks CD, Rivara FP. Mental Health Comorbidities, Household Firearm Ownership, and Firearm Access Among Children. Pediatrics. 2023 May 22:e2022060610. doi: 10.1542/peds.2022-060610. Epub ahead of print. PMID: 37212029.

Objectives: To examine how youth and their caregivers’ mental health risk factors for suicide are associated with youth firearm access inside and outside the home.

Methods: This study examines a cross-section of the Adolescent Brain and Cognitive Development Social Development study data collected from 2016 to 2021. The sample included 2277 children aged 10 to 15 years from 5 study sites across the United States. We estimated multilevel generalized linear models of household firearm ownership and the child’s reported firearm access (hard access or easy access). The primary exposures were the child’s and their caregivers’ mental health risk factors for suicide.

Results: In the Adolescent Brain and Cognitive Development Social Development study sample, approximately 20% of children lived in a firearm-owning household and 5% of all children reported easy firearm access. In non-firearm-owning households, children with diagnosed lifetime suicidality were 2.48 times more likely (95% confidence interval [CI], 1.50-4.10) than their counterparts to report easy firearm access. In firearm-owning households, children of caregivers who self-reported any mental health history or externalizing problems were 1.67 times (95% CI, 1.10-2.54) and 2.28 times (95% CI, 1.55-3.37) more likely than their counterparts to report easy firearm access.

Conclusions: Youths with mental health risk factors for suicide may be just as likely or more likely to report firearm access as those without such risk factors. Youth suicide prevention efforts should address youths’ firearm access outside the home and caregiver mental health.

Brieant A, Vannucci A, Nakua H, Harris J, Lovell J, Brundavanam D, Tottenham N, Gee DG. Characterizing the dimensional structure of early-life adversity in the Adolescent Brain Cognitive Development (ABCD) Study. Dev Cogn Neurosci. 2023 May 18;61:101256. doi: 10.1016/j.dcn.2023.101256. Epub ahead of print. PMID: 37210754.

Early-life adversity has profound consequences for youth neurodevelopment and adjustment; however, experiences of adversity are heterogeneous and interrelated in complex ways that can be difficult to operationalize and organize in developmental research. We sought to characterize the underlying dimensional structure of co-occurring adverse experiences among a subset of youth (ages 9-10) from the Adolescent Brain Cognitive Development (ABCD) Study (N = 7115), a community sample of youth in the United States. We identified 60 environmental and experiential variables that reflect adverse experiences. Exploratory factor analysis identified 10 robust dimensions of early-life adversity co-occurrence, corresponding to conceptual domains such as caregiver substance use and biological caregiver separation, caregiver psychopathology, caregiver lack of support, and socioeconomic disadvantage / neighborhood lack of safety. These dimensions demonstrated distinct associations with internalizing problems, externalizing problems, cognitive flexibility, and inhibitory control. Non-metric multidimensional scaling characterized qualitative similarity among the 10 identified dimensions. Results supported a nonlinear three-dimensional structure representing early-life adversity, including continuous gradients of “perspective”, “environmental uncertainty”, and “acts of omission/commission”. Our findings suggest that there are distinct dimensions of early-life adversity co-occurrence in the ABCD sample at baseline, and the resulting dimensions may have unique implications for neurodevelopment and youth behavior.

Hughes DE, Kunitoki K, Elyounssi S, Luo M, Bazer OM, Hopkinson CE, Dowling KF, Doyle AE, Dunn EC, Eryilmaz H, Gilman JM, Holt DJ, Valera EM, Smoller JW, Cecil CAM, Tiemeier H, Lee PH, Roffman JL. Genetic patterning for child psychopathology is distinct from that for adults and implicates fetal cerebellar development. Nat Neurosci. 2023 May 18. doi: 10.1038/s41593-023-01321-8. Epub ahead of print. PMID: 37202553.

Childhood psychiatric symptoms are often diffuse but can coalesce into discrete mental illnesses during late adolescence. We leveraged polygenic scores (PGSs) to parse genomic risk for childhood symptoms and to uncover related neurodevelopmental mechanisms with transcriptomic and neuroimaging data. In independent samples (Adolescent Brain Cognitive Development, Generation R) a narrow cross-disorder neurodevelopmental PGS, reflecting risk for attention deficit hyperactivity disorder, autism, depression and Tourette syndrome, predicted psychiatric symptoms through early adolescence with greater sensitivity than broad cross-disorder PGSs reflecting shared risk across eight psychiatric disorders, the disorder-specific PGS individually or two other narrow cross-disorder (Compulsive, Mood-Psychotic) scores. Neurodevelopmental PGS-associated genes were preferentially expressed in the cerebellum, where their expression peaked prenatally. Further, lower gray matter volumes in cerebellum and functionally coupled cortical regions associated with psychiatric symptoms in mid-childhood. These findings demonstrate that the genetic underpinnings of pediatric psychiatric symptoms differ from those of adult illness, and implicate fetal cerebellar developmental processes that endure through childhood.

Di Biase MA, Tian YE, Bethlehem RAI, Seidlitz J, Alexander-Bloch AF, Yeo BTT, Zalesky A. Mapping human brain charts cross-sectionally and longitudinally. Proc Natl Acad Sci U S A. 2023 May 16;120(20):e2216798120. doi: 10.1073/pnas.2216798120. Epub 2023 May 8. PMID: 37155868; PMCID: PMC10193972.

Brain scans acquired across large, age-diverse cohorts have facilitated recent progress in establishing normative brain aging charts. Here, we ask the critical question of whether cross-sectional estimates of age-related brain trajectories resemble those directly measured from longitudinal data. We show that age-related brain changes inferred from cross-sectionally mapped brain charts can substantially underestimate actual changes measured longitudinally. We further find that brain aging trajectories vary markedly between individuals and are difficult to predict with population-level age trends estimated cross-sectionally. Prediction errors relate modestly to neuroimaging confounds and lifestyle factors. Our findings provide explicit evidence for the importance of longitudinal measurements in ascertaining brain development and aging trajectories.

Merikangas KR, Salum GA. Editorial: Shifting the Landscape of Child Psychiatric Epidemiology. J Am Acad Child Adolesc Psychiatry. 2023 May 16:S0890-8567(23)00244-7. doi: 10.1016/j.jaac.2023.05.006. Epub ahead of print. PMID: 37201711.

The results of recent surveys that show high levels of symptoms of anxiety and depression have generated widespread concern about the mental health of US youth. Although such increases and their causes require immediate action, these symptoms alone do not indicate an epidemic of mental disorders in the US because they do not reflect mental disorders that are characterized by protracted duration and educational or social impairment. Unfortunately, there are no recent comparable data on the full range of common mental disorders. (e.g., Anxiety, Attention Deficit Hyperactivity Disorder, Major Depression, etc.) in nationally representative samples of US youth to provide a baseline for the reported increased distress in recent surveys. Therefore, we must rely on indirect information derived from surveys of subsets of symptoms and behaviors or of restricted age groups, and web-based samples with unknown biases and limited generalizability. This editorial describes how the findings from a recent report of prevalence of mental disorders in 9-10-year-old youths from the ABCD study can contribute to the national profile of mental disorders in youth. We highlight the need to address the lack of systematic data on youth emotional and behavioral disorders in the US through concerted efforts to coordinate the multi-agency sources of data on youth mental health. This will require harmonization of sampling and methods, informed application of internet-based tools based on systematic sampling and non-probability sampling methods and promotion of efforts to bridge the gap between population-based research and interventions at both the societal and individual levels.

Holt-Gosselin B, Keding TJ, Poulin R, Brieant A, Rueter A, Hendrickson TJ, Perrone A, Byington N, Houghton A, Miranda-Dominguez O, Feczko E, Fair DA, Joormann J, Gee DG. Neural Circuit Markers of Familial Risk for Depression Among Healthy Youths in the Adolescent Brain Cognitive Development (ABCD) Study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2023 May 12:S2451-9022(23)00120-9. doi: 10.1016/j.bpsc.2023.05.001. Epub ahead of print. PMID: 37182734.

Background: Family history of depression is a robust predictor of early-onset depression, which may confer risk through alterations in neural circuits implicated in reward and emotional processing. These alterations may be evident in youth at familial risk for depression, who do not currently have depression. However, the identification of robust and replicable findings has been hindered by few studies and small sample sizes. The present study sought to identify functional connectivity (FC) patterns associated with familial risk for depression.

Methods: Participants include healthy (i.e., no lifetime psychiatric diagnoses) youth at high familial risk for depression (HR, n=754; at least one parent with a history of depression) and healthy youth at low familial risk (LR, n=1,745; no parental history of psychopathology) aged 9-10 from the Adolescent Brain Cognitive Development (ABCD) Study. We conducted whole-brain seed-to-voxel analyses to examine group differences in resting-state FC with the amygdala, caudate, nucleus accumbens, and putamen. We hypothesized that HR youth would exhibit global amygdala hyperconnectivity and striatal hypoconnectivity patterns, primarily driven by maternal risk.

Results: HR youth exhibited weaker caudate-angular gyrus FC than LR youth (α=0.04, Cohen’s d=0.17). HR youth with a history of maternal depression specifically exhibited weaker caudate-angular gyrus FC (α=0.03, Cohen’s d=0.19), as well as weaker caudate-dorsolateral prefrontal cortex FC (α=0.04, Cohen’s d=0.21), than LR youth.

Conclusions: Weaker striatal connectivity may relate to heightened familial risk for depression, primarily driven by maternal history. Identifying brain-based markers of depression risk in youth can inform approaches to improve early detection, diagnosis, and treatment.

Polack RG, Mollick JA, Keren H, Joormann J, Watts R. Neural responses to reward valence and magnitude from pre- to early adolescence. Neuroimage. 2023 May 11:120166. doi: 10.1016/j.neuroimage.2023.120166. Epub ahead of print. PMID: 37178821.

Background Neural activation during reward processing is thought to underlie critical behavioral changes that take place during the transition to adolescence (e.g., learning, risk-taking). Though literature on the neural basis of reward processing in adolescence is booming, important gaps remain. First, more information is needed regarding changes in functional neuroanatomy in early adolescence. Another gap is understanding whether sensitivity to different aspects of the incentive (e.g., magnitude and valence) changes during the transition into adolescents. We used fMRI from a large sample of preadolescent children to characterize neural responses to reward valence vs. magnitude during anticipation and feedback, and their change over a period of two years. Methods Data was taken from the Adolescent Cognitive and Brain DevelopmentSM (ABCD®) study release 3.0. Children completed the Monetary Incentive Delay task at baseline (ages 9-10) and year 2 follow-up (ages 11-12). Based on data from two sites (N=491), we identified activation-based Regions of Interest (ROIs; e.g., striatum, prefrontal regions, etc.) that were sensitive to trial type (win $5, win $0.20, neutral, lose $0.20, lose $5) during anticipation and feedback phases. Then, in an independent subsample (N=1470), we examined whether these ROIs were sensitive to valence and magnitude and whether that sensitivity changed over two years. Results Our results show that most ROIs involved in reward processing (including the striatum, prefrontal cortex, and insula) are specialized, i.e., mainly sensitive to either incentive valence or magnitude, and this sensitivity was consistent over a 2-year period. The effect sizes of time and its interactions were significantly smaller (0.002≤η2≤0.02) than the effect size of trial type (0.06≤η2≤0.30). Interestingly, specialization was moderated by reward processing phase but was stable across development. Biological sex and pubertal status differences were few and inconsistent. Developmental changes were mostly evident during success feedback, where neural reactivity increased over time. Conclusions Our results suggest sub-specialization to valence vs. magnitude within many ROIs of the reward circuitry. Additionally, in line with theoretical models of adolescent development, our results suggest that the ability to benefit from success increases from pre- to early adolescence. These findings can inform educators and clinicians and facilitate empirical research of typical and atypical motivational behaviors during a critical time of development.

Moore DM, Conway ARA. The Structure of Cognitive Abilities and Associations with Problem Behaviors in Early Adolescence: An Analysis of Baseline Data from the Adolescent Brain Cognitive Development Study. J Intell. 2023 May 10;11(5):90. doi: 10.3390/jintelligence11050090. PMID: 37233339.

Using baseline data (n = 9875) from the Adolescent Brain Cognitive Development (ABCD) Study examining children aged 9 to 10 years, the current analyses included: (1) exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) of neurocognitive measures administered during baseline collection, and (2) linear regression analyses on the Child Behavior Checklist (CBCL), controlling for demographic and socioeconomic factors. The neurocognitive tasks measured episodic memory, executive function (EF; attention), language skills, processing speed, working memory, visuospatial ability, and reasoning. The CBCL included composite scores of parent-reported internalizing, externalizing, and stress-related behavior problems. The study reported here serves as an extension of prior research using a principal components analysis (PCA) of the ABCD baseline data. We propose an alternative solution using factor analysis. Analyses revealed a three-factor structure: verbal ability (VA), executive function/processing speed (EF/PS), and working memory/episodic memory (WM/EM). These factors were significantly correlated with the CBCL scores, albeit with small effect sizes. These findings provide a novel three-factor solution to the structure of cognitive abilities measured in the ABCD Study, offering new insights into the association between cognitive function and problem behaviors in early adolescence.

Halbreich ED, Callina K, King EK, Mueller MK. Companion animals and profiles of peer social behavior in adolescence. J Adolesc. 2023 May 10. doi: 10.1002/jad.12183. Epub ahead of print. PMID: 37165514.

Introduction: Relationships with companion animals have been associated with higher levels of prosocial behavior and lower levels of socioemotional difficulties for children and adolescents. Companion animals may be supportive of developing prosocial behavior in youth through practice with positive social interactions and the development of empathy and reciprocity skills. The goal of this study was to use a person-centered approach to investigate if living with a pet (including pet species) is associated with profiles of adolescent peer social behaviors (i.e., prosocial, aggressive), and size of their peer network.

Methods: This study used data from the Adolescent Brain Cognitive Development (ABCD) Study®, a large, nationally representative data set of American adolescents.

Results: In a cross-sectional sample of 5218 adolescents, we found that youth clustered into four different distinct profiles of peer social behavior. Female youth living with dogs were less likely to be in the High Aggression profile as compared to youth without pets or youth with other types of pets. However, having a pet was not associated with whether youth were in the profiles characterized by prosocial behaviors or size of peer network.

Conclusions: Overall, future research should explore how gender intersects with companion animal interactions-both in terms of frequency of interactions as well as relationship quality/emotional attachment-as well as examine these relationships over time to assess causality.

García-Marín LM, Reyes-Pérez P, Diaz-Torres S, Medina-Rivera A, Martin NG, Mitchell BL, Rentería ME. Shared molecular genetic factors influence subcortical brain morphometry and Parkinson’s disease risk. NPJ Parkinsons Dis. 2023 May 10;9(1):73. doi: 10.1038/s41531-023-00515-y. PMID: 37164954.

Parkinson’s disease (PD) is a late-onset and genetically complex neurodegenerative disorder. Here we sought to identify genes and molecular pathways underlying the associations between PD and the volume of ten brain structures measured through magnetic resonance imaging (MRI) scans. We leveraged genome-wide genetic data from several cohorts, including the International Parkinson’s Disease Genomics Consortium (IPDG), the UK Biobank, the Adolescent Brain Cognitive Development (ABCD) study, the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), the Enhancing Neuroimaging Genetics through Meta-Analyses (ENIGMA), and 23andMe. We observed significant positive genetic correlations between PD and intracranial and subcortical brain volumes. Genome-wide association studies (GWAS) – pairwise analyses identified 210 genomic segments with shared aetiology between PD and at least one of these brain structures. Pathway enrichment results highlight potential links with chronic inflammation, the hypothalamic-pituitary-adrenal pathway, mitophagy, disrupted vesicle-trafficking, calcium-dependent, and autophagic pathways. Investigations for putative causal genetic effects suggest that a larger putamen volume could influence PD risk, independently of the potential causal genetic effects of intracranial volume (ICV) on PD. Our findings suggest that genetic variants influencing larger intracranial and subcortical brain volumes, possibly during earlier stages of life, influence the risk of developing PD later in life.

Pearlman AT, Murphy MA, Raiciulescu S, Gray JC, Klein DA, Schvey NA. The prospective relationship between weight-based discrimination and eating pathology among youth. Eat Behav. 2023 May 10;49:101746. doi: 10.1016/j.eatbeh.2023.101746. Epub ahead of print. PMID: 37196505.

Among adults and adolescents, weight-based discrimination is associated with disordered eating. However, these relationships remain understudied in children. Given that weight-based discrimination is commonly reported among youth, and that childhood is a crucial developmental period for the onset of disordered eating, the current study assessed prospective associations between weight-based discrimination and eating pathology among participants in the Adolescent Brain Cognitive Development Study. At the one-year visit, children indicated whether they had experienced discrimination due to their weight within the past year. Parents completed a computerized clinical interview to determine the presence of sub-or-full threshold eating disorders (AN, BN, and BED) among their children. At the two-year visit, children completed the same assessment. Height and fasting weight were obtained. Logistic regressions, adjusting for age, sex, race/ethnicity, family income, BMI%ile, and parent-reported presence of the respective eating disorder at one-year, were conducted to assess the associations between weight-based discrimination and eating pathology. Participants were 10,299 children who completed measures at both the one- and two-year visits (Mage at one-year: 10.92 ± 0.64, 47.6 % female, 45.9 % racial/ethnic minority). The presence of weight-based discrimination, reported by 5.6 % (n = 574) of children, was significantly associated with a greater likelihood of reporting AN, BN, and BED one-year later (ORs: 1.94-4.91). Findings suggest that weight-based discrimination may confer additional risk for the onset of disordered eating, above and beyond the contribution of body weight. Intersectional research is needed to examine the role of multiple forms of discrimination in relation to the development of eating pathology.

Loughnan RJ, Palmer CE, Thompson WK, Dale AM, Jernigan TL, Chieh Fan C. Intelligence Polygenic Score Is More Predictive of Crystallized Measures: Evidence From the Adolescent Brain Cognitive Development (ABCD) Study. Psychol Sci. 2023 May 5:9567976231160702. doi: 10.1177/09567976231160702. Epub ahead of print. PMID: 37146216.

Findings in adults have shown that crystallized measures of intelligence, which are more culturally sensitive than fluid intelligence measures, have greater heritability; however, these results have not been found in children. The present study used data from 8,518 participants between 9 and 11 years old from the Adolescent Brain Cognitive Development (ABCD) Study. We found that polygenic predictors of intelligence test performance (based on genome-wide association meta-analyses of data from 269,867 individuals) and of educational attainment (based on data from 1.1 million individuals) predicted neurocognitive performance. We found that crystallized measures were more strongly associated with both polygenic predictors than were fluid measures. This mirrored heritability differences reported previously in adults and suggests similar associations in children. This may be consistent with a prominent role of gene-environment correlation in cognitive development measured by crystallized intelligence tests. Environmental and experiential mediators may represent malleable targets for improving cognitive outcomes.

Pelham WE 3rd, Tapert SF, Zúñiga ML, Thompson WK, Wade NE, Gonzalez MR, Patel H, Baker FC, Dowling GJ, Van Rinsveld AM, Baskin-Sommers A, Kiss O, Brown SA. Pandemic-Related Changes in the Prevalence of Early Adolescent Alcohol and Drug Use, 2020-2021: Data From a Multisite Cohort Study. J Adolesc Health. 2023 May 4:S1054-139X(23)00150-7. doi: 10.1016/j.jadohealth.2023.02.040. Epub ahead of print. PMID: 37191599.

Purpose: Evaluate changes in early adolescent substance use from May 2020 to May 2021 during the coronavirus disease 2019 pandemic using data from a prospective nationwide cohort: the Adolescent Brain Cognitive Development Study.

Methods: In 2018-2019, 9,270 youth aged 11.5-13.0 completed a prepandemic assessment of past-month alcohol and drug use, then up to seven during-pandemic assessments between May 2020 and May 2021. We compared the prevalence of substance use among same-age youth across these eight timepoints.

Results: Pandemic-related decreases in the past-month prevalence of alcohol use were detectable in May 2020, grew larger over time, and remained substantial in May 2021 (0.3% vs. 3.2% prepandemic, p <.001). Pandemic-related increases in inhalant use (p = .04) and prescription drug misuse (p < .001) were detectable in May 2020, shrunk over time, and were smaller but still detectable in May 2021(0.1%-0.2% vs. 0% pre-pandemic). Pandemic-related increases in nicotine use were detectable between May 2020 and March 2021 and no longer significantly different from prepandemic levels in May 2021 (0.5% vs. 0.2% prepandemic, p = .09). There was significant heterogeneity in pandemic-related change in substance use at some timepoints, with increased rates among youth identified as Black or Hispanic or in lower-income families versus stable or decreased rates among youth identified as White or in higher-income families.

Discussion: Among youth ages 11.5-13.0 years old, rates of alcohol use remained dramatically reduced in May 2021 relative to prepandemic and rates of prescription drug misuse and inhalant use remained modestly increased. Differences remained despite the partial restoration of prepandemic life, raising questions about whether youth who spent early adolescence under pandemic conditions may exhibit persistently different patterns of substance use.

Zhou Y, Pat N, Neale MC. Associations between resting state functional brain connectivity and childhood anhedonia: A reproduction and replication study. PLoS One. 2023 May 4;18(5):e0277158. doi: 10.1371/journal.pone.0277158. PMID: 37141274.

Background: Previously, a study using a sample of the Adolescent Brain Cognitive Development (ABCD)® study from the earlier 1.0 release found differences in several resting state functional MRI (rsfMRI) brain connectivity measures associated with children reporting anhedonia. Here, we aim to reproduce, replicate, and extend the previous findings using data from the later ABCD study 4.0 release, which includes a significantly larger sample.

Methods: To reproduce and replicate the previous authors’ findings, we analyzed data from the ABCD 1.0 release (n = 2437), from an independent subsample from the newer ABCD 4.0 release (excluding individuals from the 1.0 release) (n = 6456), and from the full ABCD 4.0 release sample (n = 8866). Additionally, we assessed whether using a multiple linear regression approach could improve replicability by controlling for the effects of comorbid psychiatric conditions and sociodemographic covariates.

Results: While the previously reported associations were reproducible, effect sizes for most rsfMRI measures were drastically reduced in replication analyses (including for both t-tests and multiple linear regressions) using the ABCD 4.0 (excluding 1.0) sample. However, 2 new rsfMRI measures (the Auditory vs. Right Putamen and the Retrosplenial-Temporal vs. Right-Thalamus-Proper measures) exhibited replicable associations with anhedonia and stable, albeit small, effect sizes across the ABCD samples, even after accounting for sociodemographic covariates and comorbid psychiatric conditions using a multiple linear regression approach.

Conclusion: The most statistically significant associations between anhedonia and rsfMRI connectivity measures found in the ABCD 1.0 sample tended to be non-replicable and inflated. Contrastingly, replicable associations exhibited smaller effects with less statistical significance in the ABCD 1.0 sample. Multiple linear regressions helped assess the specificity of these findings and control the effects of confounding covariates.

Li ZA, Samara A, Ray MK, Rutlin J, Raji CA, Shimony JS, Sun P, Song SK, Hershey T, Eisenstein SA. Childhood obesity is linked to putative neuroinflammation in brain white matter, hypothalamus, and striatum. Cereb Cortex Commun. 2023 May 2;4(2):tgad007. doi: 10.1093/texcom/tgad007. PMID: 37207193; PMCID: PMC10191798.

Neuroinflammation is both a consequence and driver of overfeeding and weight gain in rodent obesity models. Advances in magnetic resonance imaging (MRI) enable investigations of brain microstructure that suggests neuroinflammation in human obesity. To assess the convergent validity across MRI techniques and extend previous findings, we used diffusion basis spectrum imaging (DBSI) to characterize obesity-associated alterations in brain microstructure in 601 children (age 9-11 years) from the Adolescent Brain Cognitive DevelopmentSM Study. Compared with children with normal-weight, greater DBSI restricted fraction (RF), reflecting neuroinflammation-related cellularity, was seen in widespread white matter in children with overweight and obesity. Greater DBSI-RF in hypothalamus, caudate nucleus, putamen, and, in particular, nucleus accumbens, correlated with higher baseline body mass index and related anthropometrics. Comparable findings were seen in the striatum with a previously reported restriction spectrum imaging (RSI) model. Gain in waist circumference over 1 and 2 years related, at nominal significance, to greater baseline RSI-assessed restricted diffusion in nucleus accumbens and caudate nucleus, and DBSI-RF in hypothalamus, respectively. Here we demonstrate that childhood obesity is associated with microstructural alterations in white matter, hypothalamus, and striatum. Our results also support the reproducibility, across MRI methods, of findings of obesity-related putative neuroinflammation in children.

Weissman DG, Hatzenbuehler ML, Cikara M, Barch DM, McLaughlin KA. State-level macro-economic factors moderate the association of low income with brain structure and mental health in U.S. children. Nat Commun. 2023 May 2;14(1):2085. doi: 10.1038/s41467-023-37778-1. PMID: 37130880; PMCID: PMC10154403.

Watts R, Rader L, Grant J, Filippi CG. Genetic and Environmental Contributions to Subcortical Gray Matter Microstructure and Volume in the Developing Brain. Behav Genet. 2023 May;53(3):208-218. doi: 10.1007/s10519-023-10142-1. Epub 2023 Apr 26. PMID: 37129746.

Using baseline (ages 9-10) and two-year follow-up (ages 11-12) data from monozygotic and dizygotic twins enrolled in the longitudinal Adolescent Brain Cognitive DevelopmentSM Study, we investigated the genetic and environmental contributions to microstructure and volume of nine subcortical gray matter regions. Microstructure was assessed using diffusion MRI data analyzed using restriction spectrum imaging (RSI) and diffusion tensor imaging (DTI) models. The highest heritability estimates (estimate [95% confidence interval]) for microstructure were found using the RSI model in the pallidum (baseline: 0.859 [0.818, 0.889], follow-up: 0.835 [0.787, 0.871]), putamen (baseline: 0.859 [0.819, 0.889], follow-up: 0.874 [0.838, 0.902]), and thalamus (baseline: 0.855 [0.814, 0.887], follow-up: 0.819 [0.769, 0.857]). For volumes the corresponding regions were the caudate (baseline: 0.831 [0.688, 0.992], follow-up: 0.848 [0.701, 1.011]) and putamen (baseline: 0.906 [0.875, 0.914], follow-up: 0.906 [0.885, 0.923]). The subcortical regions displayed high genetic stability (rA = 0.743-1.000) across time and exhibited unique environmental correlations (rE = 0.194-0.610). Individual differences in both gray matter microstructure and volumes can be largely explained by additive genetic effects in this sample.

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.

Voepel-Lewis T, Senger-Carpenter T, Chen B, Seng J, Cofield C, Ploutz-Snyder R, Scott EL. Associations of Co-occurring Symptom Trajectories With Sex, Race, Ethnicity, and Health Care Utilization in Children. JAMA Netw Open. 2023 May 1;6(5):e2314135. doi: 10.1001/jamanetworkopen.2023.14135. PMID: 37200032.

Importance: Co-occurring physical and psychological symptoms during childhood and early adolescence may increase risk of symptom persistence into adulthood.

Objective: To describe co-occurring pain, psychological, and sleep disturbance symptom (pain-PSS) trajectories in a diverse cohort of children and the association of symptom trajectory with health care utilization.

Design, setting, and participants: This cohort study was a secondary analysis of longitudinal data from the Adolescent Brain Cognitive Development (ABCD) Study, collected between 2016 and 2022 at 21 research sites across the US. Participants included children with 2 to 4 complete annual symptom assessments. Data were analyzed from November 2022 to March 2023.

Main outcomes and measures: Four-year symptom trajectories were derived from multivariate latent growth curve analyses. Pain-PSS scores, including depression and anxiety, were measured using subscales from the Child Behavior Checklist and the Sleep Disturbance Scale of Childhood. Nonroutine medical care and mental health care utilization were measured using medical history and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) items.

Results: A total of 11 473 children (6018 [52.5%] male; mean [SD] age at baseline, 9.91 [0.63] years) were included in analyses. Four no pain-PSS and 5 pain-PSS trajectories were supported with good or excellent model fit (predicted probabilities, 0.87-0.96). Most children (9327 [81.3%]) had asymptomatic or low, intermittent, or single symptom trajectories. Approximately 1 in 5 children (2146 [18.7%]) had moderate to high co-occurring symptom trajectories that persisted or worsened. Compared with White children, there was a lower relative risk of having moderate to high co-occurring symptom trajectories among Black children (adjusted relative risk ratio [aRRR] range, 0.15-0.38), Hispanic children (aRRR range, 0.58-0.67), and children who identified as another race (including American Indian, Asian, Native Hawaiian, and other Pacific Islader; aRRR range, 0.43-0.59). Less than half of children with moderate to high co-occurring symptom trajectories used nonroutine health care, despite higher utilization compared with asymptomatic children (nonroutine medical care: adjusted odds ratio [aOR], 2.43 [95% CI, 1.97-2.99]; mental health services: aOR, 26.84 [95% CI, 17.89-40.29]). Black children were less likely to report nonroutine medical care (aOR, 0.61 [95% CI, 0.52-0.71]) or mental health care (aOR, 0.68 [95% CI, 0.54-0.87]) than White children, while Hispanic children were less likely to have used mental health care (aOR, 0.59 [95% CI, 0.47-0.73]) than non-Hispanic children. Lower household income was associated with lower odds of nonroutine medical care (aOR, 0.87 [95% CI, 0.77-0.99]) but not mental health care.

Conclusions and relevance: These findings suggest there is a need for innovative and equitable intervention approaches to decrease the potential for symptom persistence during adolescence.

Kaltenhauser S, Weber CF, Lin H, Mozayan A, Malhotra A, Constable RT, Acosta JN, Falcone GJ, Taylor SN, Ment LR, Sheth KN, Payabvash S. Association of Body Mass Index and Waist Circumference With Imaging Metrics of Brain Integrity and Functional Connectivity in Children Aged 9 to 10 Years in the US, 2016-2018. JAMA Netw Open. 2023 May 1;6(5):e2314193. doi: 10.1001/jamanetworkopen.2023.14193. PMID: 37200030.

Importance: Aside from widely known cardiovascular implications, higher weight in children may have negative associations with brain microstructure and neurodevelopment.

Objective: To evaluate the association of body mass index (BMI) and waist circumference with imaging metrics that approximate brain health.

Design, setting, and participants: This cross-sectional study used data from the Adolescent Brain Cognitive Development (ABCD) study to examine the association of BMI and waist circumference with multimodal neuroimaging metrics of brain health in cross-sectional and longitudinal analyses over 2 years. From 2016 to 2018, the multicenter ABCD study recruited more than 11 000 demographically representative children aged 9 to 10 years in the US. Children without any history of neurodevelopmental or psychiatric disorders were included in this study, and a subsample of children who completed 2-year follow-up (34%) was included for longitudinal analysis.

Exposures: Children’s weight, height, waist circumference, age, sex, race and ethnicity, socioeconomic status, handedness, puberty status, and magnetic resonance imaging scanner device were retrieved and included in the analysis.

Main outcomes and measures: Association of preadolescents’ BMI z scores and waist circumference with neuroimaging indicators of brain health: cortical morphometry, resting-state functional connectivity, and white matter microstructure and cytostructure.

Results: A total of 4576 children (2208 [48.3%] female) at a mean (SD) age of 10.0 years (7.6 months) were included in the baseline cross-sectional analysis. There were 609 (13.3%) Black, 925 (20.2%) Hispanic, and 2565 (56.1%) White participants. Of those, 1567 had complete 2-year clinical and imaging information at a mean (SD) age of 12.0 years (7.7 months). In cross-sectional analyses at both time points, higher BMI and waist circumference were associated with lower microstructural integrity and neurite density, most pronounced in the corpus callosum (fractional anisotropy for BMI and waist circumference at baseline and second year: P < .001; neurite density for BMI at baseline: P < .001; neurite density for waist circumference at baseline: P = .09; neurite density for BMI at second year: P = .002; neurite density for waist circumference at second year: P = .05), reduced functional connectivity in reward- and control-related networks (eg, within the salience network for BMI and waist circumference at baseline and second year: P < .002), and thinner brain cortex (eg, for the right rostral middle frontal for BMI and waist circumference at baseline and second year: P < .001). In longitudinal analysis, higher baseline BMI was most strongly associated with decelerated interval development of the prefrontal cortex (left rostral middle frontal: P = .003) and microstructure and cytostructure of the corpus callosum (fractional anisotropy: P = .01; neurite density: P = .02).

Conclusions and relevance: In this cross-sectional study, higher BMI and waist circumference among children aged 9 to 10 years were associated with imaging metrics of poorer brain structure and connectivity as well as hindered interval development. Future follow-up data from the ABCD study can reveal long-term neurocognitive implications of excess childhood weight. Imaging metrics that had the strongest association with BMI and waist circumference in this population-level analysis may serve as target biomarkers of brain integrity in future treatment trials of childhood obesity.

Wiglesworth A, Falke CA, Fiecas M, Luciana M, Cullen KR, Klimes-Dougan B. Brain signatures in children who contemplate suicide: learning from the large-scale ABCD study. Psychol Med. 2023 Apr;53(5):2164-2173. doi: 10.1017/S0033291721004074. Epub 2021 Nov 17. PMID: 37310327.

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.

Waszczuk MA, Miao J, Docherty AR, Shabalin AA, Jonas KG, Michelini G, Kotov R. General v. specific vulnerabilities: polygenic risk scores and higher-order psychopathology dimensions in the Adolescent Brain Cognitive Development (ABCD) Study. Psychol Med. 2023 Apr;53(5):1937-1946. doi: 10.1017/S0033291721003639. Epub 2021 Sep 14. PMID: 37310323.

Background: Polygenic risk scores (PRSs) capture genetic vulnerability to psychiatric conditions. However, PRSs are often associated with multiple mental health problems in children, complicating their use in research and clinical practice. The current study is the first to systematically test which PRSs associate broadly with all forms of childhood psychopathology, and which PRSs are more specific to one or a handful of forms of psychopathology.

Methods: The sample consisted of 4717 unrelated children (mean age = 9.92, s.d. = 0.62; 47.1% female; all European ancestry). Psychopathology was conceptualized hierarchically as empirically derived general factor (p-factor) and five specific factors: externalizing, internalizing, neurodevelopmental, somatoform, and detachment. Partial correlations explored associations between psychopathology factors and 22 psychopathology-related PRSs. Regressions tested which level of the psychopathology hierarchy was most strongly associated with each PRS.

Results: Thirteen PRSs were significantly associated with the general factor, most prominently Chronic Multisite Pain-PRS (r = 0.098), ADHD-PRS (r = 0.079), and Depression-PRS (r = 0.078). After adjusting for the general factor, Depression-PRS, Neuroticism-PRS, PTSD-PRS, Insomnia-PRS, Chronic Back Pain-PRS, and Autism-PRS were not associated with lower order factors. Conversely, several externalizing PRSs, including Adventurousness-PRS and Disinhibition-PRS, remained associated with the externalizing factor (|r| = 0.040-0.058). The ADHD-PRS remained uniquely associated with the neurodevelopmental factor (r = 062).

Conclusions: PRSs developed to predict vulnerability to emotional difficulties and chronic pain generally captured genetic risk for all forms of childhood psychopathology. PRSs developed to predict vulnerability to externalizing difficulties, e.g. disinhibition, tended to be more specific in predicting behavioral problems. The results may inform translation of existing PRSs to pediatric research and future clinical practice.

Taylor RL, Rogers CE, Smyser CD, Barch DM. Associations Between Preterm Birth, Inhibitory Control-Implicated Brain Regions and Tracts, and Inhibitory Control Task Performance in Children: Consideration of Socioeconomic Context. Child Psychiatry Hum Dev. 2023 Apr 29. doi: 10.1007/s10578-023-01531-y. Epub ahead of print. PMID: 37119410.

Preterm birth (PTB) is associated with increased risk for unfavorable outcomes such as deficits in attentional control and related brain structure alterations. Crucially, PTB is more likely to occur within the context of poverty. The current study examined associations between PTB and inhibitory control (IC) implicated brain regions/tracts and task performance, as well as the moderating role of early life poverty on the relation between PTB and IC-implicated regions/tracts/task performance. 2,899 children from the ABCD study were sampled for this study. Mixed effects models examined the relation between PTB and subsequent IC performance as well as prefrontal gray matter volume, white matter fractional anisotropy (FA), and mean diffusivity (MD). Household income was examined as a moderator. PTB was significantly associated with less improvement in IC task performance over time and decreased FA in left uncinate fasciculus (UF) and cingulum bundle (CB). Early life poverty moderated the relation between PTB and both CB FA and UF MD.

Retzler C, Hallam G, Johnson S, Retzler J. Person-centred Approaches to Psychopathology in the ABCD Study: Phenotypes and Neurocognitive Correlates. Res Child Adolesc Psychopathol. 2023 Apr 29. doi: 10.1007/s10802-023-01065-w. Epub ahead of print. PMID: 37119331.

Issues with classifying psychopathology using narrow diagnostic categories have prompted calls for the use of dimensional approaches. Yet questions remain about how closely dimensional approaches reflect the way symptoms cluster in individuals, whether known risk factors (e.g. preterm birth) produce distinct symptom phenotypes, and whether profiles reflecting symptom clusters are associated with neurocognitive factors. To identify distinct profiles of psychopathology, latent class analysis was applied to the syndrome scales of the parent-reported Child Behaviour Checklist for 11,381 9- and 10- year-olds from the Adolescent Brain Cognitive Development study. Four classes were identified, reflecting different profiles, to which children were assigned probabilistically; Class 1 (88.6%) reflected optimal functioning; Class 2 (7.1%), predominantly internalising; Class 3 (2.4%), predominantly externalising; and Class 4 (1.9%), universal difficulties. To investigate the presence of a possible preterm behavioural phenotype, the proportion of participants allocated to each class was cross-tabulated with gestational age category. No profile was specific to preterm birth. Finally, to assess the neurocognitive factors associated with class membership, elastic net regressions were conducted revealing a relatively distinct set of neurocognitive factors associated with each class. Findings support the use of large datasets to identify psychopathological profiles, explore phenotypes, and identify associated neurocognitive factors.

Olfson M, Wall MM, Wang S, Laje G, Blanco C. Treatment of US Children With Attention-Deficit/Hyperactivity Disorder in the Adolescent Brain Cognitive Development Study. JAMA Netw Open. 2023 Apr;6(4):e2310999. doi: 10.1001/jamanetworkopen.2023.10999. PMID: 37115542.

Importance: Characterizing the extent and pattern of unmet needs for treatment of children with attention-deficit/hyperactivity disorder (ADHD) could help target efforts to improve access to ADHD medications and outpatient mental health care.

Objective: To describe current ADHD medication use and lifetime outpatient mental health care among a large national sample of children with ADHD.

Design, setting, and participants: This study uses cross-sectional survey data from the first wave of the Adolescent Brain and Cognitive Development Study (n = 11 723), conducted from June 1, 2016, to October 15, 2018, among 1206 school children aged 9 and 10 years who met parent-reported Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for current ADHD. Statistical analysis was performed from March 23, 2022, to March 10, 2023.

Main outcomes and measures: Current ADHD medications including stimulants and nonstimulants, lifetime outpatient mental health care, or either treatment. Weighted results are reported.

Results: Among a sample of 11 723 children, 1206 had parent-reported ADHD (aged 9-10 years; 826 boys [68.2%]; 759 White, non-Hispanic children [62.2%]), 149 (12.9%) were currently receiving ADHD medications. Children receiving ADHD medications included a significantly higher percentage of boys (15.7% [121 of 826]) than girls (7.0% [28 of 108]), White children (14.8% [104 of 759]) than Black children (9.4% [22 of 206]), children of parents without a high school education (32.2% [9 of 36]) than of parents with a bachelor’s degree or higher (11.5% [84 of 715]), and children with the combined subtype of ADHD (17.0% [83 of 505]) than with the inattentive subtype (9.5% [49 of 523]). Approximately 26.2% of children (301 of 1206) with parent-reported ADHD had ever received outpatient mental health care. Children receiving outpatient mental health care included a significantly higher percentage of children whose parents had a high school education (36.2% [29 of 90]) or some college (31.0% [109 of 364]) than a bachelor’s degree or higher (21.3% [153 of 715]), children with family incomes of less than $25 000 (36.5% [66 of 176]) or $25 000 to $49 999 (27.7% [47 of 174]) than $75 000 or more (20.1% [125 of 599]), and children with the combined subtype of ADHD (33.6% [166 of 505]) than with the predominantly inattentive subtype (20.0% [101 of 523]) or the hyperactive-impulsive subtype (22.4% [34 of 178]) of ADHD.

Conclusions and relevance: This cross-sectional study of children with parent-reported ADHD suggests that most were not receiving ADHD medications and had never received outpatient mental health care. Gaps in treatment, which were not directly associated with socioeconomic disadvantage, underscore the challenges of improving communication and access to outpatient mental health care for children with ADHD.

Mendes SL, Pinaya WHL, Pan PM, Jackowski AP, Bressan RA, Sato JR. Generalizability of 3D CNN models for age estimation in diverse youth populations using structural MRI. Sci Rep. 2023 Apr 27;13(1):6886. doi: 10.1038/s41598-023-33920-7. PMID: 37106035.

Recently, several studies have investigated the neurodevelopment of psychiatric disorders using brain data acquired via structural magnetic resonance imaging (sMRI). These analyses have shown the potential of sMRI data to provide a relatively precise characterization of brain structural biomarkers. Despite these advances, a relatively unexplored question is how reliable and consistent a model is when assessing subjects from other independent datasets. In this study, we investigate the performance and generalizability of the same model architecture trained from distinct datasets comprising youths in diverse stages of neurodevelopment and with different mental health conditions. We employed models with the same 3D convolutional neural network (CNN) architecture to assess autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), brain age, and a measure of dimensional psychopathology, the Child Behavior Checklist (CBCL) total score. The investigated datasets include the Autism Brain Imaging Data Exchange II (ABIDE-II, N = 580), Attention Deficit Hyperactivity Disorder (ADHD-200, N = 922), Brazilian High-Risk Cohort Study (BHRCS, N = 737), and Adolescent Brain Cognitive Development (ABCD, N = 11,031). Models’ performance and interpretability were assessed within each dataset (for diagnosis tasks) and inter-datasets (for age estimation). Despite the demographic and phenotypic differences of the subjects, all models presented significant estimations for age (p value < 0.001) within and between datasets. In addition, most models showed a moderate to high correlation in age estimation. The results, including the models’ brain regions of interest (ROI), were analyzed and discussed in light of the youth neurodevelopmental structural changes. Among other interesting discoveries, we found that less confounded training datasets produce models with higher generalization capacity.

Shyfuddin Ahmed, Miguel Ángel Cano, Mariana Sánchez, Nan Hu, Raul Gonzalez & Gladys Ibañez (2023). Effect of maternal hypertensive disorder on their children’s neurocognitive functioning in mediated via low birthweight and BMI not by brain cortical thickness. Applied Neuropsychology: Child, DOI: 10.1080/21622965.2023.2206029

The aim of the study was to examine the association between prenatal exposure to maternal Hypertensive disorder during pregnancy (HDP) on brain structure and neurocognitive functioning (NCF) in singleton children aged between 9 and 10 years using the baseline wave of the Adolescent Brain and Cognitive Development (ABCD) Study. The ABCD Study® interviewed each child (and their parents), measured NCF, and performed neuroimaging. Exposure to maternal high blood pressure (HBP) and preeclampsia or eclampsia (PE/EL) were extracted from the developmental history questionnaire. Differences in cortical thickness (CTh) and five cognitive abilities (two executive functions, working and episodic memory, processing speed, and two language abilities) between exposed and unexposed children were examined using generalized linear models. The mediating effects of CTh, birthweight, and BMI on the relationship between maternal HDP on NCF were also examined. A total of 584-children exposed to HBP, 387-children exposed to PE/EL, and 5,877 unexposed children were included in the analysis. Neither CTh nor NCF differed between the exposed and unexposed children with or without adjusting for the confounders including the child’s age, sex, race, education, and birth histories. The whole-brain CTh did not mediate the relationships between HDP and NCF. However, the relationship between HDP and most of the NCF was mediated by the child’s birthweight and BMI. Exposure to maternal HDP can affect their offspring’s later-life cognitive abilities via low birthweight and BMI during childhood. Prospective longitudinal studies, following up from infancy, are needed to further delineate the association of HDP on children’s cognitive abilities.

Menken MS, Rodriguez Rivera PJ, Isaiah A, Ernst T, Cloak CC, Chang L. Longitudinal alterations in brain morphometry mediated the effects of bullying victimization on cognitive development in preadolescents. Dev Cogn Neurosci. 2023 Apr 25;61:101247. doi: 10.1016/j.dcn.2023.101247. Epub ahead of print. PMID: 37119589.

Bullying victimization is associated with a doubled risk of attempting suicide in adulthood. Two longitudinal brain morphometry studies identified the fusiform gyrus and putamen as vulnerable to bullying. No study identified how neural alterations may mediate the effect of bullying on cognition. We assessed participants with caregiver-reported bullying (N = 323) and matched non-bullied controls (N = 322) from the Adolescent Brain Cognitive Development Study dataset to identify changes in brain morphometry associated with ongoing bullying victimization over two years and determine whether such alterations mediated the effect of bullying on cognition. Bullied children (38.7% girls, 47.7% racial minorities, 9.88 ± 0.62 years at baseline) had poorer cognitive performance (P < 0.05), larger right hippocampus (P = 0.036), left entorhinal cortex, left superior parietal cortex, and right fusiform gyrus volumes (all P < 0.05), as well as larger surface areas in multiple other frontal, parietal, and occipital cortices. Thinner cortices were also found in the left hemisphere, particularly in the left temporal lobe, and right frontal region (all P < 0.05). Importantly, larger surface area in the fusiform cortices partially suppressed (12-16%), and thinner precentral cortices partially mitigated, (7%) the effect of bullying on cognition (P < 0.05). These findings highlight the negative impact of prolonged bullying victimization on brain morphometry and cognition.

Wilson S, Fan CC, Hewitt J. ABCD Behavior Genetics: Twin, Family, and Genomic Studies Using the Adolescent Brain Cognitive Development (ABCD) Study Dataset. Behav Genet. 2023 Apr 25. doi: 10.1007/s10519-023-10144-z. Epub ahead of print. PMID: 37095243.

Fan CC, Loughnan R, Wilson S, Hewitt JK; ABCD Genetic Working Group. Genotype Data and Derived Genetic Instruments of Adolescent Brain Cognitive Development Study® for Better Understanding of Human Brain Development. Behav Genet. 2023 May;53(3):159-168. doi: 10.1007/s10519-023-10143-0. Epub 2023 Apr 24. PMID: 37093311.

Xie, C., Xiang, S., Shen, C. et al. A shared neural basis underlying psychiatric comorbidity. Nat Med (2023). https://doi.org/10.1038/s41591-023-02317-4

Recent studies proposed a general psychopathology factor underlying common comorbidities among psychiatric disorders. However, its neurobiological mechanisms and generalizability remain elusive. In this study, we used a large longitudinal neuroimaging cohort from adolescence to young adulthood (IMAGEN) to define a neuropsychopathological (NP) factor across externalizing and internalizing symptoms using multitask connectomes. We demonstrate that this NP factor might represent a unified, genetically determined, delayed development of the prefrontal cortex that further leads to poor executive function. We also show this NP factor to be reproducible in multiple developmental periods, from preadolescence to early adulthood, and generalizable to the resting-state connectome and clinical samples (the ADHD-200 Sample and the Stratify Project). In conclusion, we identify a reproducible and general neural basis underlying symptoms of multiple mental health disorders, bridging multidimensional evidence from behavioral, neuroimaging and genetic substrates. These findings may help to develop new therapeutic interventions for psychiatric comorbidities.

A general neuropsychopathological factor underlying many mental illnesses. Nat Med (2023). https://doi.org/10.1038/s41591-023-02319-2

By using several large population-based and clinical neuroimaging cohorts, we identified a shared neural basis for several mental disorders, namely the neuropsychopathological factor. This genetically determined factor might represent a delayed development of prefrontal brain neural circuits, leading to poor executive function.

Green, R., Kirkland, A., Browning, B., Bryant, B., Garcia, A., Tomko, R., . . . Squeglia, L. (2023). 325 Predictors of Substance Use Initiation by Late Childhood: Findings from the Adolescent Brain Cognitive Development (ABCD) Study. Journal of Clinical and Translational Science, 7(S1), 97-97. doi:10.1017/cts.2023.374

OBJECTIVES/GOALS: Adolescence represents a critical period for substance use initiation. Various factors may contribute to trying a sip or single puff of a substance, that could lead to more frequent use. However, less is known about how predictors from multiple domains converge to impact risk for general substance use initiation. METHODS/STUDY POPULATION: The Adolescent Brain Cognitive Development (ABCD) study is a multi-site longitudinal study following youth into early adulthood. The present study included 7,644 ABCD children who reported no lifetime substance use (including any experimentation) at baseline (ages 9–10). Our primary aim was to use a random forest classification model to predict binary substance use initiation, defined as trying any non-prescribed substance (e.g., alcohol, tobacco, cannabis, non-prescribed medications), during a 2-year follow-up after baseline. A total of 402 variables from the following categories were examined as predictors: demographics, peer substance use and availability, mental and physical health, culture and environment, biospecimens, neurocognitive functioning, and structural neuroimaging variables. RESULTS/ANTICIPATED RESULTS: Over a two-year follow-up, 751 (9.8%) of substance-naïve children reported trying a substance by age 11. The most common substance was alcohol, followed by cannabis and tobacco. Mean Decrease Accuracy (MDA) values were used to assess the relative importance of each predictor. The overall accuracy of the model in accurately predicting group membership (no substance use initiation vs. substance use initiation) was 57.66%. Of the top 5 predictors, the most important predictor was intent to use alcohol (MDA = .002). The following top predictors were structural neuroimaging variables: volume and surface area of right lateral occipital lobe (MDA = .0009 and .0008, respectively), surface area of right inferior temporal lobe (MDA = .0007), and surface area of left superior frontal lobe (MDA = .0007). DISCUSSION/SIGNIFICANCE: A combination of intent to use alcohol and structural neuroimaging indices were among the top predictors of substance use initiation. Understanding predictors of early substance use experimentation is important for identifying at-risk youth that may require targeted intervention approaches.

Nagata JM, Singh G, Yang JH, Smith N, Kiss O, Ganson KT, Testa A, Jackson DB, Baker FC. Bedtime screen use behaviors and sleep outcomes: Findings from the Adolescent Brain Cognitive Development (ABCD) Study. Sleep Health. 2023 Apr 21:S2352-7218(23)00034-7. doi: 10.1016/j.sleh.2023.02.005. Epub ahead of print. PMID: 37098449.

Objectives: To determine associations between bedtime screen time behaviors and sleep outcomes in a national study of early adolescents.

Methods: We analyzed cross-sectional data from 10,280 early adolescents aged 10-14 (48.8% female) in the Adolescent Brain Cognitive Development Study (Year 2, 2018-2020). Regression analyses examined the association between self-reported bedtime screen use and self- and caregiver-reported sleep measures, including sleep disturbance symptoms, controlling for sex, race/ethnicity, household income, parent education, depression, data collection period (pre- vs. during COVID-19 pandemic), and study site.

Results: Overall, 16% of adolescents had at least some trouble falling or staying asleep in the past 2 weeks and 28% had overall sleep disturbance, based on caregiver reports. Adolescents who had a television or an Internet-connected electronic device in the bedroom had a greater risk of having trouble falling or staying asleep (adjusted risk ratio 1.27, 95% CI 1.12-1.44) and overall sleep disturbance (adjusted risk ratio 1.15, 95% CI 1.06-1.25). Adolescents who left their phone ringer activated overnight had more trouble falling/staying asleep and greater overall sleep disturbance compared to those who turned off their cell phones at bedtime. Streaming movies, playing video games, listening to music, talking/texting on the phone, and using social media or chat rooms were all associated with trouble falling/staying asleep and sleep disturbance.

Conclusions: Several bedtime screen use behaviors are associated with sleep disturbances in early adolescents. The study’s findings can inform guidance for specific bedtime screen behaviors among early adolescents.

Gordon EM, Chauvin RJ, Van AN, Rajesh A, Nielsen A, Newbold DJ, Lynch CJ, Seider NA, Krimmel SR, Scheidter KM, Monk J, Miller RL, Metoki A, Montez DF, Zheng A, Elbau I, Madison T, Nishino T, Myers MJ, Kaplan S, Badke D’Andrea C, Demeter DV, Feigelis M, Ramirez JSB, Xu T, Barch DM, Smyser CD, Rogers CE, Zimmermann J, Botteron KN, Pruett JR, Willie JT, Brunner P, Shimony JS, Kay BP, Marek S, Norris SA, Gratton C, Sylvester CM, Power JD, Liston C, Greene DJ, Roland JL, Petersen SE, Raichle ME, Laumann TO, Fair DA, Dosenbach NUF. A somato-cognitive action network alternates with effector regions in motor cortex. Nature. 2023 Apr 19. doi: 10.1038/s41586-023-05964-2. Epub ahead of print. PMID: 37076628.

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations1,2, despite evidence for concentric functional zones3 and maps of complex actions4. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action5 and physiological control6, arousal7, errors8 and pain9. This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions4 and connectivity to internal organs10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate-isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement.

Cullen B, Gameroff MJ, Ward J, Bailey MES, Lyall DM, Lyall LM, MacSweeney N, Murphy E, Sangha N, Shen X, Strawbridge RJ, van Dijk MT, Zhu X, Smith DJ, Talati A, Whalley HC, Cavanagh J, Weissman MM. Cognitive Function in People With Familial Risk of Depression. JAMA Psychiatry. 2023 Apr 19. doi: 10.1001/jamapsychiatry.2023.0716. Epub ahead of print. PMID: 37074691.

Importance: Cognitive impairment in depression is poorly understood. Family history of depression is a potentially useful risk marker for cognitive impairment, facilitating early identification and targeted intervention in those at highest risk, even if they do not themselves have depression. Several research cohorts have emerged recently that enable findings to be compared according to varying depths of family history phenotyping, in some cases also with genetic data, across the life span.

Objective: To investigate associations between familial risk of depression and cognitive performance in 4 independent cohorts with varied depth of assessment, using both family history and genetic risk measures.

Design, setting, and participants: This study used data from the Three Generations at High and Low Risk of Depression Followed Longitudinally (TGS) family study (data collected from 1982 to 2015) and 3 large population cohorts, including the Adolescent Brain Cognitive Development (ABCD) study (data collected from 2016 to 2021), National Longitudinal Study of Adolescent to Adult Health (Add Health; data collected from 1994 to 2018), and UK Biobank (data collected from 2006 to 2022). Children and adults with or without familial risk of depression were included. Cross-sectional analyses were conducted from March to June 2022.

Exposures: Family history (across 1 or 2 prior generations) and polygenic risk of depression.

Main outcomes and measures: Neurocognitive tests at follow-up. Regression models were adjusted for confounders and corrected for multiple comparisons.

Results: A total of 57 308 participants were studied, including 87 from TGS (42 [48%] female; mean [SD] age, 19.7 [6.6] years), 10 258 from ABCD (4899 [48%] female; mean [SD] age, 12.0 [0.7] years), 1064 from Add Health (584 [49%] female; mean [SD] age, 37.8 [1.9] years), and 45 899 from UK Biobank (23 605 [51%] female; mean [SD] age, 64.0 [7.7] years). In the younger cohorts (TGS, ABCD, and Add Health), family history of depression was primarily associated with lower performance in the memory domain, and there were indications that this may be partly associated with educational and socioeconomic factors. In the older UK Biobank cohort, there were associations with processing speed, attention, and executive function, with little evidence of education or socioeconomic influences. These associations were evident even in participants who had never been depressed themselves. Effect sizes between familial risk of depression and neurocognitive test performance were largest in TGS; the largest standardized mean differences in primary analyses were -0.55 (95% CI, -1.49 to 0.38) in TGS, -0.09 (95% CI, -0.15 to -0.03) in ABCD, -0.16 (95% CI, -0.31 to -0.01) in Add Health, and -0.10 (95% CI, -0.13 to -0.06) in UK Biobank. Results were generally similar in the polygenic risk score analyses. In UK Biobank, several tasks showed statistically significant associations in the polygenic risk score analysis that were not evident in the family history models.

Conclusions and relevance: In this study, whether assessed by family history or genetic data, depression in prior generations was associated with lower cognitive performance in offspring. There are opportunities to generate hypotheses about how this arises through genetic and environmental determinants, moderators of brain development and brain aging, and potentially modifiable social and lifestyle factors across the life span.

Wade NE, McCabe CJ, Wallace AL, Gonzalez MR, Hoh E, Infante MA, Mejia MH, Haist F. Clouding Up Cognition? Secondhand Cannabis and Tobacco Exposure Related to Cognitive Functioning in Youth. Biol Psychiatry Glob Open Sci. 2022 Feb 22;3(2):233-242. doi: 10.1016/j.bpsgos.2022.01.010. PMID: 37124351; PMCID: PMC10140452.

Background: Increasing legalization of cannabis, in addition to longstanding rates of tobacco use, raises concerns for possible cognitive decrements from secondhand smoke or environmental exposure, although 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 = 5580; 48% female) cognitive performance and secondhand or environmental cannabis or tobacco exposure data were 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- and 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 (p = .008) skills. 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. Because, to our knowledge, this is the first known study of its kind and thus preliminary, secondhand cannabis should continue to be investigated to confirm results.

Moreau AL, Voss M, Hansen I, Paul SE, Barch DM, Rogers CE, Bogdan R. Prenatal Selective Serotonin Reuptake Inhibitor Exposure, Depression, and Brain Morphology in Middle Childhood: Results From the ABCD Study. Biol Psychiatry Glob Open Sci. 2022 Feb 26;3(2):243-254. doi: 10.1016/j.bpsgos.2022.02.005. PMID: 37124359; PMCID: PMC10140451.

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.

Gorelik AJ, Paul SE, Karcher NR, Johnson EC, Nagella I, Blaydon L, Modi H, Hansen IS, Colbert SMC, Baranger DAA, Norton SA, Spears I, Gordon B, Zhang W, Hill PL, Oltmanns TF, Bijsterbosch JD, Agrawal A, Hatoum AS, Bogdan R. A Phenome-Wide Association Study (PheWAS) of Late Onset Alzheimer Disease Genetic Risk in Children of European Ancestry at Middle Childhood: Results from the ABCD Study. Behav Genet. 2023 Apr 18. doi: 10.1007/s10519-023-10140-3. Epub ahead of print. PMID: 37071275.

Genetic risk for Late Onset Alzheimer Disease (AD) has been associated with lower cognition and smaller hippocampal volume in healthy young adults. However, whether these and other associations are present during childhood remains unclear. Using data from 5556 genomically-confirmed European ancestry youth who completed the baseline session of the ongoing the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®), our phenome-wide association study estimating associations between four indices of genetic risk for late-onset AD (i.e., AD polygenic risk scores (PRS), APOE rs429358 genotype, AD PRS with the APOE region removed (ADPRS-APOE), and an interaction between ADPRS-APOE and APOE genotype) and 1687 psychosocial, behavioral, and neural phenotypes revealed no significant associations after correction for multiple testing (all ps > 0.0002; all pfdr > 0.07). These data suggest that AD genetic risk may not phenotypically manifest during middle-childhood or that effects are smaller than this sample is powered to detect.

Razban RM, Pachter JA, Dill KA, Mujica-Parodi LR. Early path dominance as a principle for neurodevelopment. Proc Natl Acad Sci U S A. 2023 Apr 18;120(16):e2218007120. doi: 10.1073/pnas.2218007120. Epub 2023 Apr 13. PMID: 37053187.

We perform targeted attack, a systematic computational unlinking of the network, to analyze its effects on global communication across the brain network through its giant cluster. Across diffusion magnetic resonance images from individuals in the UK Biobank, Adolescent Brain Cognitive Development Study and Developing Human Connectome Project, we find that targeted attack procedures on increasing white matter tract lengths and densities are remarkably invariant to aging and disease. Time-reversing the attack computation suggests a mechanism for how brains develop, for which we derive an analytical equation using percolation theory. Based on a close match between theory and experiment, our results demonstrate that tracts are limited to emanate from regions already in the giant cluster and tracts that appear earliest in neurodevelopment are those that become the longest and densest.

Olfson M, Wall M, Wang S, Blanco C. Prevalence and Correlates of Mental Disorders in Children Aged 9 and 10 Years: Results From the ABCD Study. J Am Acad Child Adolesc Psychiatry. 2023 Apr 12:S0890-8567(23)00178-8. doi: 10.1016/j.jaac.2023.04.005. Epub ahead of print. PMID: 37062398.

Objective: To estimate the prevalence of current DSM-5 disorders in children, ages 9 to 10 years, and their associations with sociodemographic and physical characteristics.

Method: In this analysis of the Adolescent Brain Cognitive Development (ABCD) first wave study data, current child mental disorders were based on the computerized parent version of the Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5 (N=11,874) supplemented with the child version for mood and selected anxiety disorders and with teacher Brief Problem Monitor ratings for the attention and externalizing scales. Child sociodemographic (race/ethnicity, nativity, parental marital status, parental education, family income) and physical characteristics (sex, pubertal stage, weight status, maternal age) were derived from parent report and anthropometric measurement. Odds ratios (OR) with 95% Confidence Intervals (95%CI) assessed associations with child mental disorders.

Results: The prevalence of any current mental disorder was 10.11% including 11.48% among boys and 8.68% among girls. After controlling for several sociodemographic and physical characteristics, boys (OR=1.53; 95%CI=1.17-1.99), children from families with incomes below $25,000 (OR=2.05; 95%CI=1.31-3.22), incomes of $25,000-$49,000 (OR=1.90; 95%CI=1.20-3.00) ($75,000, reference) and obese children (OR=1.45, 95%CI=1.16-1.81) (healthy weight, reference) were at increased risk for any current child mental disorder. Children from the lowest family income group were at particularly high risk for ADHD (OR=3.86, 95%CI=1.69-8.79) and disruptive behavior behaviors (OR=4.13; 95%CI=1.86-9.15).

Conclusion: These patterns underscore the importance of strengthening service planning, preventive interventions, and etiological research focused on children from low income families.

Wen, X., Shu, Y., Qu, D. et al. Associations of bullying perpetration and peer victimization subtypes with preadolescent’s suicidality, non-suicidal self-injury, neurocognition, and brain development. BMC Med 21, 141 (2023). https://doi.org/10.1186/s12916-023-02808-8

Background
Although both peer victimization and bullying perpetration negatively impact preadolescents’ development, the underlying neurobiological mechanism of this adverse relationship remains unclear. Besides, the specific psycho-cognitive patterns of different bullying subtypes also need further exploration, warranting large-scale studies on both general bullying and specific bullying subtypes.

Methods
We adopted a retrospective methodology by utilizing the data from the Adolescent Brain and Cognitive DevelopmentSM Study (ABCD Study®) cohort collected between July 2018 and January 2021. Participants were preadolescents aged from 10 to 13 years. The main purpose of our study is to examine the associations of general and specific peer victimization/bullying perpetration with preadolescents’ (1) suicidality and non-suicidal self-injury; (2) executive function and memory, including attention inhibition, processing speed, emotion working memory, and episodic memory; (3) brain structure abnormalities; and (4) brain network disturbances. Age, sex, race/ethnicity, body mass index (BMI), socioeconomic status (SES), and data acquisition site were included as covariates.

Results
A total of 5819 participants aged from 10 to 13 years were included in this study. Higher risks of suicide ideation, suicide attempt, and non-suicidal self-injury were found to be associated with both bullying perpetration/peer victimization and their subtypes (i.e., overt, relational, and reputational). Meanwhile, poor episodic memory was shown to be associated with general victimization. As for perpetration, across all four tasks, significant positive associations of relational perpetration with executive function and episodic memory consistently manifested, yet opposite patterns were shown in overt perpetration. Notably, distinct psycho-cognitive patterns were shown among different subtypes. Additionally, victimization was associated with structural brain abnormalities in the bilateral paracentral and posterior cingulate cortex. Furthermore, victimization was associated with brain network disturbances between default mode network and dorsal attention network, between default mode network and fronto-parietal network, and ventral attention network related connectivities, including default mode network, dorsal attention network, cingulo-opercular network, cingulo-parietal network, and sensorimotor hand network. Perpetration was also associated with brain network disturbances between the attention network and the sensorimotor hand network.

Conclusions
Our findings offered new evidence for the literature landscape by emphasizing the associations of bullying experiences with preadolescents’ clinical characteristics and cognitive functions, while distinctive psycho-cognitive patterns were shown among different subtypes. Additionally, there is evidence that these associations are related to neurocognitive brain networks involved in attention control and episodic retrieval. Given our findings, future interventions targeting ameliorating the deleterious effect of bullying experiences on preadolescents should consider their subtypes and utilize an ecosystemic approach involving all responsible parties.

Brislin SJ, Clark DA, Clark DB, Durbin CE, Parr AC, Ahonen L, Anderson-Carpenter KD, Heitzeg MM, Luna B, Sripada C, Zucker RA, Hicks BM. Differential Item Functioning in Reports of Delinquent Behavior Between Black and White Youth: Evidence of Measurement Bias in Self-Reports of Arrest in the Adolescent Brain Cognitive Development Study. Assessment. 2023 Apr 11:10731911231164627. doi: 10.1177/10731911231164627. Epub ahead of print. PMID: 37039543.

Youth self-reports are a mainstay of delinquency assessment; however, making valid inferences about delinquency using these assessments requires equivalent measurement across groups of theoretical interest. We examined whether a brief 10-item delinquency measure exhibited measurement invariance across non-Hispanic White (n = 6,064) and Black (n = 1,666) youth (ages 10-11 years old) in the Adolescent Brain Cognitive Developmentsm Study (ABCD Study®). We detected differential item functioning (DIF) in two items. Black youth were more likely to report being arrested or picked up by police than White youth with the same score on the latent delinquency trait. Although multiple covariates (income, urgency, and callous-unemotional traits) reduced mean-level difference in overall delinquency, they were generally unrelated to the DIF in the Arrest item. However, the DIF in the Arrest item was reduced in size and no longer significant after adjusting for neighborhood safety. Results illustrate the importance of considering measurement invariance when using self-reported delinquency scores to draw inferences about group differences, and the utility of measurement invariance analyses for helping to identify mechanisms that contribute to group differences generally.

Rader L, Freis SM, Friedman NP. Associations Between Adolescent Pain and Psychopathology in the Adolescent Brain Cognitive Development (ABCD) Study. Behav Genet. 2023 Apr 10. doi: 10.1007/s10519-023-10138-x. Epub ahead of print. PMID: 37036551.

Pain and psychopathology co-occur in adolescence, but the directionality and etiology of these associations are unclear. Using the pain questionnaire and the Child Behavior Checklist from the Adolescent Brain Cognitive Development study (n = 10,414 children [770 twin pairs] aged 12-13), we estimated longitudinal, co-twin control, and twin models to evaluate the nature of these associations. In two-wave cross-lag panel models, there were small cross-lag effects that suggested bidirectional associations. However, the co-twin control models suggested that most associations were familial. Pain at age 12 and 13 was mostly environmental (A = 0-12%, C = 15-30%, E = 70-73%) and the twin models suggested that associations with psychopathology were primarily due to shared environmental correlations. The exception was externalizing, which had a phenotypic prospective effect on pain, a significant within-family component, and a non-shared environmental correlation at age 12. Environmental risk factors may play a role in pain-psychopathology co-occurrence. Future studies can examine risk factors such as stressful life events.

Carrión-Castillo A, Paz-Alonso PM, Carreiras M. Brain structure, phenotypic and genetic correlates of reading performance. Nat Hum Behav. 2023 Apr 10. doi: 10.1038/s41562-023-01583-z. Epub ahead of print. PMID: 37037991.

Reading is an evolutionarily recent development that recruits and tunes brain circuitry connecting primary- and language-processing regions. We investigated whether metrics of the brain’s physical structure correlate with reading performance and whether genetic variants affect this relationship. To this aim, we used the Adolescent Brain Cognitive Development dataset (n = 9,013) of 9-10-year-olds and focused on 150 measures of cortical surface area (CSA) and thickness. Our results reveal that reading performance is associated with nine measures of brain structure including relevant regions of the reading network. Furthermore, we show that this relationship is partially mediated by genetic factors for two of these measures: the CSA of the entire left hemisphere and, specifically, of the left superior temporal gyrus CSA. These effects emphasize the complex and subtle interplay between genes, brain and reading, which is a partly heritable polygenic skill that relies on a distributed network.

Li R, Lopez DA, Palermo TM. Pubertal Development And Pain Incidence And Characteristics In Children: A 1-Year Prospective Cohort Study Of A National Sample. The Journal of Pain. Volume 24, Issue 4, Supplement, April 2023, Page 89. https://doi.org/10.1016/j.jpain.2023.02.255

Sex differences in pain become apparent during puberty. However, the influence of key pubertal development characteristics and pubertal hormones on pain is largely unknown. We examined the prospective associations between self-reported and hormone-indicated pubertal characteristics and pain incidence and severity in 10-11-year-old pain-free youth in the Adolescent Brain Cognitive Development (ABCD) Study over one year. Puberty was measured at baseline and follow-up with self-report (Pubertal Development Scale [PDS]) and hormonal assessment (saliva dehydroepiandrosterone [DHEA], testosterone, and estradiol). Pain status (yes/no), intensity and interference (0-10 NRS) in the past month were self-reported at follow-up. Pubertal maturity, growth, and asynchrony were examined in relation to pain onset and severity through confounder-adjusted GEE modified Poisson and linear regression models. Among 6641 pain-free youth at baseline, 1-year incident pain was 30.7%. In both sexes, higher PDS scores were associated with greater risk of pain onset (Relative Risk [RR] = 1.11-1.28, Ps<0.01). In boys, higher PDS item variance was associated with greater pain incidence (RR=1.12, 95% CI 1.04-1.21) and interference (beta=0.41, 95% CI 0.05-0.77); higher PDS overall and gonadal scores were associated with higher pain intensity (Ps<0.05). Associations with hormones were seen in boys only, with each 10-fold higher testosterone levels associated with a 42% lower risk of pain incidence (95% CI -56% to -25%) and 1.25-point lower (95% CI -2.06 to -0.44) pain intensity, and higher DHEA levels associated with lower pain intensity (P = 0.024). Relationships between pubertal development and pain in peripubertal adolescents are sex- and puberty measurement-specific and warrant further investigation. Hearst Foundation Fellowship Award (LAN: 410370600101​).

Wild M, Nestor B. Associations Among Social Behavior, Pain Intensity, And Functional Outcomes In Adolescents. The Journal of Pain. Volume 24, Issue 4, Supplement, April 2023, Page 97. https://doi.org/10.1016/j.jpain.2023.02.277

Adolescence is a critical period for social development that coincides with increased incidence of chronic conditions, including chronic pain. Further, social stressors are demonstrated to impact the experience of pain. In turn, pain can impact functional outcomes vital for successful adolescent development, including school attendance and engagement with peers. Understanding the relations among social development factors and the development of chronic pain in adolescence is therefore necessary. The purpose of the reported study was to determine the relations among self-reported social behaviors (i.e., prosocial behavior and social responsiveness), pain intensity, and school attendance outcomes (i.e., absences and presence of an Individualized Education Program (IEP)). Data from 2,022 adolescent participants in the nationally representative Adolescent Brain and Cognitive Development (ABCD) study who reported pain were used to conduct Spearman correlational and logistic regression analyses. Results indicated that pain intensity is significantly positively associated with both excused and unexcused school absences while prosocial behavior is significantly negatively associated with past or current IEP. Generalized linear model analyses demonstrated that pain severity, prosocial behavior, and social responsiveness were significantly associated with school attendance. Further, prosocial behavior (OR: 0.87, 95% CI: 0.76-0.98) and social responsiveness (OR; 1.17, 95% CI: 1.14-1.21) were significant predictors of an IEP while pain severity was not in logistic regression analyses. Taken together, the results suggest social behavior, as measured by prosocial behaviors and social responsiveness, is not significantly related to pain intensity but may be an important predictor of interest for functional impairments associated with chronic pain.

Senger-Carpenter T, Seng J, Ploutz-Snyder R, Scott E, Voepel-Lewis T. Comorbid Pain And Symptom Trajectories And Healthcare Utilization During Early Adolescence. The Journal of Pain. Volume 24, Issue 4, Supplement, April 2023, Pages 89-90. https://doi.org/10.1016/j.jpain.2023.02.257

Co-occurring pain, psychologic symptoms, and sleep disturbance during adolescence increases vulnerability to symptom persistence into adulthood. This secondary analysis used longitudinal data from the Adolescent Brain Cognitive Development (ABCD) Study® collected between 2016-2022 to describe comorbid symptom trajectories and associated healthcare utilization during early adolescence. Included were 11,473 adolescents (52.5% male; 9.91 ± 0.63 years at baseline), who completed two or more annual assessments. Pain, psychologic, and somnolence (PSS) symptoms were measured with Child Behavior Checklist and Sleep Disorder Scale of Childhood subscales. Four Pain/PSS and 5 No Pain/PSS symptom trajectories were identified with multivariate latent growth curve analyses. Eighty-one percent of participants had asymptomatic/low symptom trajectories, while 19% had medium/high symptom trajectories. Black and Hispanic children had 20-60% lower relative risk of clustering into high symptom trajectories. Fewer than half of adolescents in the highest symptom trajectories reported non-routine medical or mental healthcare. Black and Hispanic youth were less likely to utilize healthcare (i.e., 35% Black vs. 48% White had non-routine medical care, OR 0.57 [95% CI 0.43, 0.76], 25% Black vs. 36% White had mental healthcare, OR 0.58 [95% CI 0.42, 0.81], 27% Hispanic vs. 35% non-Hispanic had mental healthcare; OR 0.67 [95% CI 0.48, 0.90]) and lower household income decreased the odds of non-routine medical care (OR 0.85 [95% CI 0.75, 0.96]). Although 1 in 5 youth experienced moderate/high, comorbid symptom trajectories, non-routine medical and mental healthcare utilization was low–particularly amongst Black and Hispanic youth–suggesting a need for prompt, equitable intervention to address symptom persistence. This work was funded by the National Institute on Drug Abuse (RO1DA052310) and the National Institute for Nursing Research (NR016914).

Smith DM, Loughnan R, Friedman NP, Parekh P, Frei O, Thompson WK, Andreassen OA, Neale M, Jernigan TL, Dale AM. Heritability Estimation of Cognitive Phenotypes in the ABCD Study® Using Mixed Models. Behav Genet. 2023 Apr 7. doi: 10.1007/s10519-023-10141-2. Epub ahead of print. PMID: 37024669.

Twin and family studies have historically aimed to partition phenotypic variance into components corresponding to additive genetic effects (A), common environment (C), and unique environment (E). Here we present the ACE Model and several extensions in the Adolescent Brain Cognitive Development℠ Study (ABCD Study®), employed using the new Fast Efficient Mixed Effects Analysis (FEMA) package. In the twin sub-sample (n = 924; 462 twin pairs), heritability estimates were similar to those reported by prior studies for height (twin heritability = 0.86) and cognition (twin heritability between 0.00 and 0.61), respectively. Incorporating SNP-derived genetic relatedness and using the full ABCD Study® sample (n = 9,742) led to narrower confidence intervals for all parameter estimates. By leveraging the sparse clustering method used by FEMA to handle genetic relatedness only for participants within families, we were able to take advantage of the diverse distribution of genetic relatedness within the ABCD Study® sample.

Dhamala E, Rong Ooi LQ, Chen J, Ricard JA, Berkeley E, Chopra S, Qu Y, Zhang X, Lawhead C, Yeo BTT, Holmes AJ. Brain-based predictions of psychiatric illness-linked behaviors across the sexes. Biol Psychiatry. 2023 Apr 7:S0006-3223(23)01195-2. doi: 10.1016/j.biopsych.2023.03.025. Epub ahead of print. PMID: 37031778.

Background: Individual differences in functional brain connectivity can be used to predict both the presence of psychiatric illness and variability in associated behaviors. However, despite evidence for sex differences in functional network connectivity and in the prevalence, presentation, and trajectory of psychiatric illnesses, the extent to which disorder-relevant aspects of network connectivity are shared or unique across the sexes remains to be determined.

Methods: In this work, we used predictive modeling approaches to evaluate whether shared or unique functional connectivity correlates underlie the expression of psychiatric illness-linked behaviors in males and females in data from the Adolescent Brain Cognitive Development study (n=5260; 2571 females).

Results: We demonstrate that functional connectivity profiles predict individual differences in externalizing behaviors in males and females, but only predict internalizing behaviors in females. Furthermore, models trained to predict externalizing behaviors in males generalize to predict internalizing behaviors in females, and models trained to predict internalizing behaviors in females generalize to predict externalizing behaviors in males. Finally, the neurobiological correlates of many behaviors are largely shared within and across sexes: functional connections within and between heteromodal association networks including default, limbic, control, and dorsal attention networks are associated with internalizing and externalizing behaviors.

Conclusions: Taken together, these findings suggest that shared neurobiological patterns may manifest as distinct behaviors across the sexes. Based on these results, we recommend that both clinicians and researchers carefully consider how sex may influence the presentation of psychiatric illnesses, especially those along the internalizing-externalizing spectrum.

Loso HM, Locke Dube S, Chaarani B, Ivanova M, Garavan H, Johns MM, Potter AS. Associations Between Gender Nonconformity, School Environments, Family Conflict, and Emotional and Behavioral Health Among Children Ages 10-11. J Adolesc Health. 2023 Apr 7:S1054-139X(23)00103-9. doi: 10.1016/j.jadohealth.2023.02.008. Epub ahead of print. PMID: 37032213.

Purpose: In youth, gender nonconformity (GNC; gender expression that differs from stereotypes based on assigned sex at birth) is associated with a higher likelihood of peer and caregiver victimization and rejection. However, few studies have examined the relationship between GNC, overall family conflict, perceptions of school environment, and emotional and behavioral health problems among children ages 10-11.

Methods: The Adolescent Brain Cognitive Development Study data release 3.0 was used (n = 11,068; 47.9% female). A path analysis was used to examine whether school environment and family conflict, mediated the relationship between GNC and behavioral and emotional health outcomes.

Results: We found significant mediation of the relationship between GNC and behavioral and emotional health by school environment a2b2 = .20, 95% CI [0.13, 0.27] and family conflict a1b1 = 0.34, 95% CI [0.25, 0.42].

Discussion: Our results suggest that youth who present as gender nonconforming experience elevated family conflict, poorer perceptions of their school environment and elevated behavioral and emotional health problems. Further, the relationship between GNC and elevated emotional and behavioral health problems was mediated by perceptions of school environment and family conflict. Clinical and policy suggestions to improve environments and outcomes for youth who present as gender nonconforming are discussed.

Karcher NR, Merchant J, Rappaport BI, Barch DM. Associations with youth psychotic-like experiences over time: Evidence for trans-symptom and specific cognitive and neural risk factors. J Psychopathol Clin Sci. 2023 Apr 6. doi: 10.1037/abn0000820. Epub ahead of print. PMID: 37023280.

The current study examined whether impairments in cognitive and neural factors at baseline (ages 9-10) predict initial levels or changes in psychotic-like experiences (PLEs) and whether such impairments generalize to other psychopathology symptoms (i.e., internalizing and externalizing symptoms). Using unique longitudinal Adolescent Brain Cognitive Development Study data, the study examined three time points from ages 9 to 13. Univariate latent growth models examined associations between baseline cognitive and neural metrics with symptom measures using discovery (n = 5,926) and replication (n = 5,952) data sets. For symptom measures (i.e., PLEs, internalizing, externalizing), we examined mean initial levels (i.e., intercepts) and changes over time (i.e., slopes). Predictors included neuropsychological test performance, global structural MRI, and several a priori within-network resting-state functional connectivity metrics. Results showed a pattern whereby baseline cognitive and brain metric impairments showed the strongest associations with PLEs over time. Lower cognitive, volume, surface area, and cingulo-opercular within-network connectivity metrics showed associations with increased PLEs and higher initial levels of externalizing and internalizing symptoms. Several metrics were uniquely associated with PLEs, including lower cortical thickness with higher initial PLEs and lower default mode network connectivity with increased PLEs slopes. Neural and cognitive impairments in middle childhood were broadly associated with increased PLEs over time, and showed stronger associations with PLEs compared with other psychopathology symptoms. The current study also identified markers potentially uniquely associated with PLEs (e.g., cortical thickness). Impairments in broad cognitive metrics, brain volume and surface area, and a network associated with information integration may represent risk factors for general psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cooper R, Di Biase MA, Bei B, Quach J, Cropley V. Associations of Changes in Sleep and Emotional and Behavioral Problems From Late Childhood to Early Adolescence. JAMA Psychiatry. 2023 Jun 1;80(6):585-596. doi: 10.1001/jamapsychiatry.2023.0379. PMID: 37017952; PMCID: PMC10077137.

Importance: Sleep problems and psychopathology symptoms are highly comorbid and bidirectionally correlated across childhood and adolescence. Whether these associations are specific to discrete profiles of sleep problems and specific internalizing and externalizing phenomena is currently unclear.

Objective: To characterize individual changes in profiles of sleep problems and their prospective associations with psychopathology symptoms across the transition from childhood to adolescence.

Design, setting, and participants: This observational cohort study used baseline data (participant age of 9 to 11 years) and 2-year follow-up data (participant age of 11 to 13 years) from the community-setting, multicenter Adolescent Brain Cognitive Development (ABCD) study. Individuals were assessed for a range of sleep problems at both waves and categorized into profiles via latent profile analysis. The stability and change in these profiles over time was assessed via latent transition analysis. Logistic regression models examined whether psychopathology symptoms were cross-sectionally associated with profile membership and whether transitions between profiles were associated with changes psychopathology symptoms over time. Data were collected from September 2016 to January 2020, and data were analyzed from August 2021 to July 2022.

Exposures: Sleep problems were assessed at both baseline and follow-up via the parent-reported Sleep Disturbance Scale for Children (SDSC).

Main outcomes and measures: Psychopathology symptoms at both baseline and follow-up were assessed using the internalizing and externalizing dimension scores derived from the parent-reported Child Behavior Checklist.

Results: A total of 10 313 individuals (4913 [47.6%] were female) were categorized into 4 latent profiles of sleep problems at both baseline and follow-up: a low disturbance profile, a sleep onset/maintenance problems profile, a moderate and nonspecific disturbance profile (termed mixed disturbance), and a high disturbance profile. Individuals in the 3 more severe problem profiles displayed greater risk of concurrent internalizing symptoms (sleep onset/maintenance problems: odds ratio [OR], 1.30; 95% CI, 1.25-1.35; P < .001; mixed disturbance: OR, 1.29; 95% CI, 1.25-1.33; P < .001; high disturbance: OR, 1.44; 95% CI, 1.40-1.49; P < .001) and externalizing symptoms (sleep onset/maintenance problems: OR, 1.20; 95% CI, 1.16-1.23; P < .001; mixed disturbance: OR, 1.17; 95% CI, 1.14-1.20; P < .001; high disturbance: OR, 1.24; 95% CI, 1.21-1.28; P < .001). Transitions between sleep profiles over time were associated with prospective internalizing and externalizing symptoms, but not vice versa.

Conclusions and relevance: There are substantial changes in sleep problems across the transition to adolescence that are associated with later internalizing and externalizing symptoms. Sleep profiles could be targeted in future intervention and treatment programs to improve sleep-related and mental health-related outcomes across development.

Ahern J, Thompson W, Fan CC, Loughnan R. Comparing Pruning and Thresholding with Continuous Shrinkage Polygenic Score Methods in a Large Sample of Ancestrally Diverse Adolescents from the ABCD Study®. Behav Genet. 2023 Apr 5. doi: 10.1007/s10519-023-10139-w. Epub ahead of print. PMID: 37017779.

Using individuals’ genetic data researchers can generate Polygenic Scores (PS) that are able to predict risk for diseases, variability in different behaviors as well as anthropomorphic measures. This is achieved by leveraging models learned from previously published large Genome-Wide Association Studies (GWASs) associating locations in the genome with a phenotype of interest. Previous GWASs have predominantly been performed in European ancestry individuals. This is of concern as PS generated in samples with a different ancestry to the original training GWAS have been shown to have lower performance and limited portability, and many efforts are now underway to collect genetic databases on individuals of diverse ancestries. In this study, we compare multiple methods of generating PS, including pruning and thresholding and Bayesian continuous shrinkage models, to determine which of them is best able to overcome these limitations. To do this we use the ABCD Study, a longitudinal cohort with deep phenotyping on individuals of diverse ancestry. We generate PS for anthropometric and psychiatric phenotypes using previously published GWAS summary statistics and examine their performance in three subsamples of ABCD: African ancestry individuals (n = 811), European ancestry Individuals (n = 6703), and admixed ancestry individuals (n = 3664). We find that the single ancestry continuous shrinkage method, PRScs (CS), and the multi ancestry meta method, PRScsx Meta (CSx Meta), show the best performance across ancestries and phenotypes.

Nagata JM, Chu J, Cervantez L, Ganson KT, Testa A, Jackson DB, Murray SB, Weiser SD. Food insecurity and binge-eating disorder in early adolescence. Int J Eat Disord. 2023 Apr 4. doi: 10.1002/eat.23944. Epub ahead of print. PMID: 37013949.

Objective: Food insecurity is defined as lack of consistent access to adequate food for healthy living. The objective of this study was to determine the associations between food insecurity and binge-eating disorder in a national cohort of 9- to 14-year-old children.

Method: We analyzed prospective cohort data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 10,035, 2016-2020). Logistic regression analyses estimated the associations between food insecurity at baseline, year 1, or year 2 (exposure) and binge eating, subclinical binge-eating disorder (Other Specified Feeding and Eating Disorder-Binge-Eating Disorder [OSFED-BED]), and binge-eating disorder (BED) (outcome) based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5) at 2-year follow-up.

Results: The prevalence of food insecurity in the study was 15.8%. At 2-year follow-up, 1.71% of the sample received a diagnosis of BED or OSFED-BED, while 6.62% reported binge eating. Food insecurity was associated with 1.67 higher odds of BED or OSFED-BED (95% CI 1.04-2.69) and 1.31 higher odds of binge-eating symptoms (95% CI 1.01-1.71).

Discussion: Food insecurity in early adolescence is associated with higher odds of developing future binge-eating and BED or OSFED-BED. Clinicians may consider assessing for binge eating in adolescents with food insecurity and provide support in accessing appropriate food resources.

Public significance: Prior research has shown that food insecurity is associated with disordered eating behaviors, including binge eating in adulthood. This study explored whether food insecurity in early adolescence increases risk for developing binge-eating disorder (BED). Targeted screening for BED in adolescents experiencing FI, and vice versa, may be warranted.

Brooks SJ, Smith C, Stamoulis C. Excess BMI in early adolescence adversely impacts maturating functional circuits supporting high-level cognition and their structural correlates. Int J Obes (Lond). 2023 Apr 3. doi: 10.1038/s41366-023-01303-7. Epub ahead of print. PMID: 37012426.

Background/objectives: Adverse effects of excess BMI (affecting 1 in 5 children in the US) on brain circuits during neurodevelopmentally vulnerable periods are incompletely understood. This study investigated BMI-related alterations in maturating functional networks and their underlying brain structures, and high-level cognition in early adolescence.

Subjects/methods: Cross-sectional resting-state fMRI, structural sMRI, neurocognitive task scores, and BMI from 4922 youth [median (IQR) age = 120.0 (13.0) months, 2572 females (52.25%)] from the Adolescent Brain Cognitive Development (ABCD) cohort were analyzed. Comprehensive topological and morphometric network properties were estimated from fMRI and sMRI, respectively. Cross-validated linear regression models assessed correlations with BMI. Results were reproduced across multiple fMRI datasets.

Results: Almost 30% of youth had excess BMI, including 736 (15.0%) with overweight and 672 (13.7%) with obesity, and statistically more Black and Hispanic compared to white, Asian and non-Hispanic youth (p < 0.01). Those with obesity or overweight were less physically active, slept less than recommended, snored more frequently, and spent more time using an electronic device (p < 0.01). They also had lower topological efficiency, resilience, connectivity, connectedness and clustering in Default-Mode, dorsal attention, salience, control, limbic, and reward networks (p ≤ 0.04, Cohen’s d: 0.07-0.39). Lower cortico-thalamic efficiency and connectivity were estimated only in youth with obesity (p < 0.01, Cohen’s d: 0.09-0.19). Both groups had lower cortical thickness, volume and white matter intensity in these networks’ constituent structures, particularly anterior cingulate, entorhinal, prefrontal, and lateral occipital cortices (p < 0.01, Cohen’s d: 0.12-0.30), which also mediated inverse relationships between BMI and regional functional topologies. Youth with obesity or overweight had lower scores in a task measuring fluid reasoning – a core aspect of cognitive function, which were partially correlated with topological changes (p ≤ 0.04).

Conclusions: Excess BMI in early adolescence may be associated with profound aberrant topological alterations in maturating functional circuits and underdeveloped brain structures that adversely impact core aspects of cognitive function.

Giabbanelli PJ, Rice KL, Nataraj N, Brown MM, Harper CR. A systems science approach to identifying data gaps in national data sources on adolescent suicidal ideation and suicide attempt in the United States. BMC Public Health. 2023 Apr 1;23(1):627. doi: 10.1186/s12889-023-15320-8. PMID: 37005568.

Background: Suicide is currently the second leading cause of death among adolescents ages 10-14, and third leading cause of death among adolescents ages 15-19 in the United States (U.S). Although we have numerous U.S. based surveillance systems and survey data sources, the coverage offered by these data with regard to the complexity of youth suicide had yet to be examined. The recent release of a comprehensive systems map for adolescent suicide provides an opportunity to contrast the content of surveillance systems and surveys with the mechanisms listed in the map.

Objective: To inform existing data collection efforts and advance future research on the risk and protective factors relevant to adolescent suicide.

Methods: We examined data from U.S. based surveillance systems and nationally-representative surveys that included (1) observations for an adolescent population and (2) questions or indicators in the data that identified suicidal ideation or suicide attempt. Using thematic analysis, we evaluated the codebooks and data dictionaries for each source to match questions or indicators to suicide-related risk and protective factors identified through a recently published suicide systems map. We used descriptive analysis to summarize where data were available or missing and categorized data gaps by social-ecological level.

Results: Approximately 1-of-5 of the suicide-related risk and protective factors identified in the systems map had no supporting data, in any of the considered data sources. All sources cover less than half the factors, except the Adolescent Brain Cognitive Development Study (ABCD), which covers nearly 70% of factors.

Conclusions: Examining gaps in suicide research can help focus future data collection efforts in suicide prevention. Our analysis precisely identified where data is missing and also revealed that missing data affects some aspects of suicide research (e.g., distal factors at the community and societal level) more than others (e.g., proximal factors about individual characteristics). In sum, our analysis highlights limitations in current suicide-related data availability and provides new opportunities to identify and expand current data collection efforts.

Wiker T, Norbom LB, Beck D, Agartz I, Andreassen OA, Alnæs D, Dahl A, Eilertsen E, Moberget T, Ystrøm E, Westlye LT, Lebel C, Huster RJ, Tamnes CK. Reaction time variability in children is specifically associated with attention problems and regional white matter microstructure. Biol Psychiatry Cogn Neurosci Neuroimaging. 2023 Mar 30:S2451-9022(23)00073-3. doi: 10.1016/j.bpsc.2023.03.010. Epub ahead of print. PMID: 37003411.

Background: Increased intraindividual variability (IIV) in reaction times (RT) has been suggested as a key cognitive and behavioral marker of attention problems, but findings for other dimensions of psychopathology are less consistent. Moreover, while studies have linked IIV to brain white matter microstructure, large studies testing the robustness of these associations are needed.

Methods: We utilized data from the Adolescent Brain Cognitive Development (ABCD) Study baseline assessment to test the associations between IIV and psychopathology (n=8622, age=8.9-11.1), and between IIV and white matter microstructure (n=7958, age=8.9-11.1). IIV was investigated using an ex-Gaussian distribution analysis of RTs in correct response go trials in the stop signal task. Psychopathology was measured by the Child Behavior Checklist and a bifactor structural equation model was performed to extract a general p-factor and specific factors reflecting internalizing, externalizing, and attention problems. To investigate white matter microstructure, fractional anisotropy (FA) and mean (MD), axial (AD), and radial diffusivity (RD) were examined in 23 atlas-based tracts.

Results: Increased IIV in both short and long reaction times was positively associated with the specific attention problems factor (Cohen’s d=.13 and d=.15). Increased IIV in long reaction times was also positively associated with RD in the left and right corticospinal tract (d=.12 (both tracts)).

Conclusions: Using a large sample and a data-driven dimensional approach to psychopathology, the results provide novel evidence for a small but specific association between IIV and attention problems in children and supports previous findings on the relevance of white matter microstructure for IIV.

Kiss O, Nagata JM, de Zambotti M, Dick AS, Marshall AT, Sowell ER, Van Rinsveld A, Guillaume M, Pelham WE, Gonzalez MR, Brown SA, Dowling GJ, Lisdahl KM, Tapert SF, Baker FC. Effects of the COVID-19 pandemic on screen time and sleep in early adolescents. Health Psychol. 2023 Mar 27. doi: 10.1037/hea0001251. Epub ahead of print. PMID: 36972087.

Objective: During the COVID-19 pandemic, adolescents and families have turned to online activities and social platforms more than ever to maintain well-being, connect remotely with friends and family, and online schooling. However, excessive screen use can have negative effects on health (e.g., sleep). This study examined changes in sleep habits and recreational screen time (social media, video gaming), and their relationship, before and across the first year of the pandemic in adolescents in the Adolescent Brain Cognitive Development (ABCD) Study.

Method: Mixed-effect models were used to examine associations between self-reported sleep and screen time using longitudinal data of 5,027 adolescents in the ABCD Study, assessed before the pandemic (10-13 years) and across six time points between May 2020 and March 2021 (pandemic).

Results: Time in bed varied, being higher during May-August 2020 relative to pre-pandemic, partially related to the school summer break, before declining in October 2020 to levels lower than pre-pandemic. Screen time steeply increased and remained high across all pandemic time points relative to pre-pandemic. Higher social media use and video gaming were associated with shorter time in bed, later bedtimes, and longer sleep onset latency.

Conclusions: Sleep behavior and screen time changed during the pandemic in early adolescents. More screen time was associated with poorer sleep behavior, before and during the pandemic. While recreational screen usage is an integral component of adolescent’s activities, especially during the pandemic, excessive use can have negative effects on essential health behaviors, highlighting the need to promote balanced screen usage. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Montez DF, Van AN, Miller RL, Seider NA, Marek S, Zheng A, Newbold DJ, Scheidter K, Feczko E, Perrone AJ, Miranda-Dominguez O, Earl EA, Kay BP, Jha AK, Sotiras A, Laumann TO, Greene DJ, Gordon EM, Tisdall MD, van der Kouwe A, Fair DA, Dosenbach NUF. Using synthetic MR images for distortion correction. Dev Cogn Neurosci. 2023 Mar 24;60:101234. doi: 10.1016/j.dcn.2023.101234. Epub ahead of print. PMID: 37023632.

Functional MRI (fMRI) data acquired using echo-planar imaging (EPI) are highly distorted by magnetic field inhomogeneities. Distortion and differences in image contrast between EPI and T1-weighted and T2-weighted (T1w/T2w) images makes their alignment a challenge. Typically, field map data are used to correct EPI distortions. Alignments achieved with field maps can vary greatly and depends on the quality of field map data. However, many public datasets lack field map data entirely. Additionally, reliable field map data is often difficult to acquire in high-motion pediatric or developmental cohorts. To address this, we developed Synth, a software package for distortion correction and cross-modal image registration that does not require field map data. Synth combines information from T1w and T2w anatomical images to construct an idealized undistorted synthetic image with similar contrast properties to EPI data. This synthetic image acts as an effective reference for individual-specific distortion correction. Using pediatric (ABCD: Adolescent Brain Cognitive Development) and adult (MSC: Midnight Scan Club; HCP: Human Connectome Project) data, we demonstrate that Synth performs comparably to field map distortion correction approaches, and often outperforms them. Field map-less distortion correction with Synth allows accurate and precise registration of fMRI data with missing or corrupted field map information.

Kulisch LK, Arumäe K, Briley DA, Vainik U. Triangulating causality between childhood obesity and neurobehavior: Behavioral genetic and longitudinal evidence. Dev Sci. 2023 Mar 23:e13392. doi: 10.1111/desc.13392. Epub ahead of print. PMID: 36950909.

Childhood obesity is a serious health concern that is not yet fully understood. Previous research has linked obesity with neurobehavioral factors such as behavior, cognition, and brain morphology. The causal directions of these relationships remain mostly untested. We filled this gap by using the Adolescent Brain Cognitive Development study cohort comprising 11,875 children aged 9-10. First, correlations between the age- and sex-specific 95th BMI percentile (%BMIp95) and neurobehavioral measures were cross-sectionally analyzed. Effects were then aggregated by neurobehavioral domain for causal analyses. Behavioral genetic Direction of Causation modeling was used to test the direction of each relationship. Findings were validated by longitudinal cross-lagged panel modeling. %BMIp95 correlated with impulsivity, motivation, psychopathology, eating behavior, and cognitive tests (executive functioning, language, memory, perception, working memory). Greater %BMIp95 was also associated with reduced cortical thickness in frontal and temporal brain areas but with increased thickness in parietal and occipital areas. Similar although weaker patterns emerged for cortical surface area and volume. Behavioral genetic modeling suggested causal effects of %BMIp95 on eating behavior (β = 0.26), cognition (β = 0.05), cortical thickness (β = 0.15), and cortical surface area (β = 0.07). Personality/psychopathology (β = 0.09) and eating behavior (β = 0.16) appeared to influence %BMIp95. Longitudinal evidence broadly supported these findings. Results regarding cortical volume were inconsistent. Results supported causal effects of obesity on brain functioning and morphology. The present study highlights the importance of physical health for brain development and may inform interventions aimed at preventing or reducing pediatric obesity. RESEARCH HIGHLIGHTS: A continuous measure related to obesity, %BMIp95, has correlations with various measures of brain functioning and structure Behavioral genetic and longitudinal modeling suggest causal links from personality, psychopathology, and eating behavior to %BMIp95 Results also indicate directional links from %BMIp95 to eating behavior, cognition, cortical thickness, and cortical surface area Obesity may play a role for healthy brain development during childhood.

Nagata JM, Lee CM, Yang J, Al-Shoaibi AAA, Ganson KT, Testa A, Jackson DB. Associations between sexual orientation and early adolescent screen use: Findings from the Adolescent Brain Cognitive Development (ABCD) Study. Ann Epidemiol. 2023 Mar 23:S1047-2797(23)00053-4. doi: 10.1016/j.annepidem.2023.03.004. Epub ahead of print. PMID: 36965838.

Objective: To assess the association between sexual orientation and screen use (screen time and problematic screen use) in a demographically diverse national sample of early adolescents in the U.S.

Methods: We analyzed cross-sectional data from Year 2 of the Adolescent Brain Cognitive Development (ABCD) Study (N=10,339, 2018-2020, ages 10-14 years). Multiple linear regression analyses estimated the association between sexual orientation and recreational screen time, as well as problematic use of video games, social media, and mobile phones.

Results: In a sample of 10,339 adolescents (48.7% female, 46.0% racial/ethnic minority), sexual minority (compared to heterosexual) identification was associated with 3.72 (95% CI 2.96-4.47) more hours of daily recreational screen time, specifically more time on television, YouTube videos, video games, texting, social media, video chat, and browsing the internet. Possible sexual minority identification (responding “maybe” to the sexual minority question) was associated with 1.58 (95% CI 0.92-2.24) more hours of screen time compared to heterosexual identification. Sexual minority and possible sexual minority identification were associated with higher problematic social media, video game, and mobile phone use.

Conclusions: Sexual minority adolescents spend a disproportionate amount of time engaging in screen-based activities, which can lead to problematic screen use.

Smith KE, Wang WL, Mason TB. Facets of impulsivity and reward in relation to binge-eating disorder course of illness among children: findings from the Adolescent Brain Cognitive Development study. J Child Psychol Psychiatry. 2023 Mar 23. doi: 10.1111/jcpp.13789. Epub ahead of print. PMID: 36951577.

Background: The present study examined facets of impulsivity and reward sensitivity [as measured by the UPPS-P Impulsive Behavior Scale and Behavioral Activation and Behavioral Inhibition Scales (BIS/BAS)] as multivariable predictors of subsequent binge-eating disorder (BED) course of illness in middle childhood.

Methods: The current sample included children aged 9-10 years (N = 9,438) who took part in the baseline and 1-year follow-up assessments of the Adolescent Brain Cognitive Development (ABCD) study. BED course was operationalized as those who never developed BED or subthreshold BED (SBED) (‘control’), were diagnosed with BED/SBED at year 1 but not baseline (‘developers’), were diagnosed with BED/SBED at baseline but not year 1 (‘remitters’), or were diagnosed with BED/SBED at both times (‘maintainers’).

Results: Higher baseline BIS/BAS reward responsivity scores were related to the greater likelihood of belonging to the maintainer group relative to the control and remitter groups (ORs1.12-1.19). Regarding covariates, higher baseline body mass index percentile and internalizing symptoms were related to the greater likelihood of BED development, remittance, and maintenance compared to the control group (ORs = 1.04-1.14); no variables were uniquely related to BED development. Exploratory analyses showed that the likelihood of belonging to the maintainer group compared to the control group was greatest at higher levels of negative urgency in combination with high reward responsivity.

Conclusions: Heightened reward responsivity may convey risk for poorer BED course in children, while emotional disorder symptomatology may act as a more general risk and maintenance factor for BED.

Dooley N, Healy C, Cotter D, Clarke M, Cannon M. Predicting childhood ADHD-linked symptoms from prenatal and perinatal data in the ABCD cohort. Dev Psychopathol. 2023 Mar 22:1-14. doi: 10.1017/S0954579423000238. Epub ahead of print. PMID: 36946069.

This study investigates the capacity of pre/perinatal factors to predict attention-deficit/hyperactivity disorder (ADHD) symptoms in childhood. It also explores whether predictive accuracy of a pre/perinatal model varies for different groups in the population. We used the ABCD (Adolescent Brain Cognitive Development) cohort from the United States (N = 9975). Pre/perinatal information and the Child Behavior Checklist were reported by the parent when the child was aged 9-10. Forty variables which are generally known by birth were input as potential predictors including maternal substance-use, obstetric complications and child demographics. Elastic net regression with 5-fold validation was performed, and subsequently stratified by sex, race/ethnicity, household income and parental psychopathology. Seventeen pre/perinatal variables were identified as robust predictors of ADHD symptoms in this cohort. The model explained just 8.13% of the variance in ADHD symptoms on average (95% CI = 5.6%-11.5%). Predictive accuracy of the model varied significantly by subgroup, particularly across income groups, and several pre/perinatal factors appeared to be sex-specific. Results suggest we may be able to predict childhood ADHD symptoms with modest accuracy from birth. This study needs to be replicated using prospectively measured pre/perinatal data.

Núñez C, García-Alix A, Arca G, Agut T, Carreras N, Portella MJ, Stephan-Otto C. Breastfeeding duration is associated with larger cortical gray matter volumes in children from the ABCD study. J Child Psychol Psychiatry. 2023 Mar 22. doi: 10.1111/jcpp.13790. Epub ahead of print. PMID: 36946606.

Background: Despite the numerous studies in favor of breastfeeding for its benefits in cognition and mental health, the long-term effects of breastfeeding on brain structure are still largely unknown. Our main objective was to study the relationship between breastfeeding duration and cerebral gray matter volumes. We also explored the potential mediatory role of brain volumes on behavior.

Methods: We analyzed 7,860 magnetic resonance images of children 9-11 years of age from the Adolescent Brain Cognitive Development (ABCD) dataset in order to study the relationship between breastfeeding duration and cerebral gray matter volumes. We also obtained several behavioral data (cognition, behavioral problems, prodromal psychotic experiences, prosociality, impulsivity) to explore the potential mediatory role of brain volumes on behavior.

Results: In the 7,860 children analyzed (median age = 9 years and 11 months; 49.9% female), whole-brain voxel-based morphometry analyses revealed an association mainly between breastfeeding duration and larger bilateral volumes of the pars orbitalis and the lateral orbitofrontal cortex. In particular, the association with the left pars orbitalis and the left lateral orbitofrontal cortex proved to be very robust to the addition of potentially confounding covariates, random selection of siblings, and splitting the sample in two. The volume of the left pars orbitalis and the left lateral orbitofrontal cortex appeared to mediate the relationship between breastfeeding duration and the negative urgency dimension of the UPPS-P Impulsive Behavior Scale. Global gray matter volumes were also significant mediators for behavioral problems as measured with the Child Behavior Checklist.

Conclusions: Our findings suggest that breastfeeding is a relevant factor in the proper development of the brain, particularly for the pars orbitalis and lateral orbitofrontal cortex regions. This, in turn, may impact impulsive personality and mental health in early puberty.

Song K, Zhang J-L, et al. Youth Screen Media Activity Patterns and Associations With Behavioral Developmental Measures and Resting-state Brain Functional Connectivity. Journal of the American Academy of Child & Adolescent Psychiatry. Published: March 21, 2023. DOI:https://doi.org/10.1016/j.jaac.2023.02.014

Objective
Screen media activity (SMA) consumes considerable time in youth’s lives, raising concerns about the effects it may have on youth development. Disentangling mixed associations between youth’s SMA and developmental measures should move beyond overall screen time and consider types and patterns of SMA. We aimed to identify reliable and generalizable SMA patterns among youth and examine their associations with behavioral developmental measures and developing brain functional connectivity.

Method
Three waves of the Adolescent Brain and Cognitive Development (ABCD) data were examined. The Lifespan Human Connectome Project in Development (HCP-D) was interrogated as an independent sample. ABCD participants included 11,878 children at baseline. HCP-D participants included 652 children and adolescents. Youth-reported SMA and behavioral developmental measures (neurocognitive performance, behavioral problems, psychotic-like experiences, impulsivity, and sensitivities to punishment/reward) were assessed with validated instruments. We identified SMA patterns in the ABCD baseline data using K-means clustering and sensitivity analyses. The generalizability and stability of the identified SMA patterns were examined in HCP-D data and ABCD follow-up waves, respectively. Relationships were examined between SMA patterns and behavioral and brain (resting-state brain functional connectivity [RSFC]) measures using linear-mixed-effect modelling with false-discovery-rate (FDR) correction.

Results
SMA data from 11,815 children (Meanage = 119.0 months, SDage = 7.5; 6,159 (52.1%) boys) were examined, and 3,151 (26.7%) demonstrated a video-centric higher-frequency SMA pattern and 8,666 (73.3%) demonstrated a lower-frequency pattern. The SMA patterns were validated in similarly-aged HCP-D youth. Compared to the lower-frequency-SMA-pattern group, the video-centric-higher-frequency-SMA-pattern group showed poorer neurocognitive performance (Beta=-0.12, 95%CI, [-0.08, -0.16], FDR-corrected p<.001), more total behavioral problems (Beta=0.13, 95%CI, [0.09, 0.18], FDR-corrected p<.001), and more psychotic-like experiences (Beta=0.31, 95%CI, [0.27, 0.36], FDR-corrected p<.001). The video-centric-higher-frequency-SMA-pattern group demonstrated higher impulsivity, more sensitivity to punishment/reward and altered RSFC among brain areas implicated previously in cognitive processes. Most of the associations persisted with age in the ABCD data, with more individuals (n=3,378, 30.4%) in the video-centric higher-frequency SMA group at one-year follow-up. A social-communication-centric SMA pattern was observed in HCP-D adolescents.

Conclusion
Video-centric SMA patterns are reliable and generalizable during late childhood. A higher-frequency-video-entertainment-SMA-pattern group showed altered RSFC and poorer developmental measures that persisted longitudinally. The findings suggest public health strategies aiming to decrease excessive time spent by children on video-entertainment-related SMA are needed. Further studies are needed to examine potential video-centric/social-centric SMA bifurcation to understand dynamic changes and trajectories of SMA patterns and related outcomes developmentally.

Nagata JM, Lee CM, Yang JH, Kiss O, Ganson KT, Testa A, Jackson DB, Al-Shoaibi AAA, Baker FC. Sexual Orientation Disparities in Early Adolescent Sleep: Findings from the Adolescent Brain Cognitive Development Study. LGBT Health. 2023 Mar 21. doi: 10.1089/lgbt.2022.0268. Epub ahead of print. PMID: 36944127.

Purpose: The purpose of this study was to examine associations between sexual minority status (e.g., gay or bisexual) and sleep problems in a demographically diverse, national sample of U.S. early adolescents. Methods: We analyzed cross-sectional data from the Adolescent Brain Cognitive Development Study (Year 2, 2018-2020) to estimate associations between sexual orientation and sleep problems or disturbance, adjusting for confounders and testing potential mediators (depressive problems, stress problems, family conflict, and parental monitoring). Results: In a sample of 8563 adolescents 10- to 14-years-old, 4.4% identified as sexual minority individuals. Sexual minority status was associated with self-reported trouble falling or staying asleep (risk ratio [RR] = 2.24, 95% confidence interval [CI] = 1.88-2.68) and caregiver-reported sleep disturbance (RR = 1.50, 95% CI = 1.29-1.75). The association between sexual minority status and trouble falling or staying asleep was partially mediated by greater depressive problems, more family conflict, and less parental monitoring, whereas the association between sexual minority status and caregiver-reported sleep disturbance was partially mediated by greater depressive problems, higher stress, and greater family conflict. Conclusions: Our results indicate that sexual minority status may be linked to sleep disturbance in early adolescence. Depressive problems, stress, family conflict, and less parental monitoring partially mediate disparities in sleep health for sexual minority youth. Future research could test interventions to promote family and caregiver acceptance and mental health support for sexual minority youth to improve their sleep and other health outcomes.

Dudley JA, Maloney TC, Simon JO, Atluri G, Karalunas SL, Altaye M, Epstein JN, Tamm L. ABCD_Harmonizer: An Open-source Tool for Mapping and Controlling for Scanner Induced Variance in the Adolescent Brain Cognitive Development Study. Neuroinformatics. 2023 Mar 20. doi: 10.1007/s12021-023-09624-8. Epub ahead of print. PMID: 36940062.

Data from multisite magnetic resonance imaging (MRI) studies contain variance attributable to the scanner that can reduce statistical power and potentially bias results if not appropriately managed. The Adolescent Cognitive Brain Development (ABCD) study is an ongoing, longitudinal neuroimaging study acquiring data from over 11,000 children starting at 9-10 years of age. These scans are acquired on 29 different scanners of 5 different model types manufactured by 3 different vendors. Publicly available data from the ABCD study include structural MRI (sMRI) measures such as cortical thickness and diffusion MRI (dMRI) measures such as fractional anisotropy. In this work, we 1) quantify the variance attributable to scanner effects in the sMRI and dMRI datasets, 2) demonstrate the effectiveness of the data harmonization approach called ComBat to address scanner effects, and 3) present a simple, open-source tool for investigators to harmonize image features from the ABCD study. Scanner-induced variance was present in every image feature and varied in magnitude by feature type and brain location. For almost all features, scanner variance exceeded variability attributable to age and sex. ComBat harmonization was shown to effectively remove scanner induced variance from all image features while preserving the biological variability in the data. Moreover, we show that for studies examining relatively small subsamples of the ABCD dataset, the use of ComBat harmonized data provides more accurate estimates of effect sizes compared to controlling for scanner effects using ordinary least squares regression.

Zhao Y, Paulus MP, Potenza MN. Brain structural co-development is associated with internalizing symptoms two years later in the ABCD cohort. J Behav Addict. 2023 Mar 20. doi: 10.1556/2006.2023.00006. Epub ahead of print. PMID: 36940096.

Background and aims: About 1/3 of youth spend more than four hours/day engaged in screen media activity (SMA). This investigation utilized longitudinal brain imaging and mediation analyses to examine relationships among SMA, brain patterns, and internalizing problems.

Methods: Data from Adolescent Brain Cognitive Development (ABCD) participants with baseline and two-year follow-up structural imaging data that passed quality control (N = 5,166; 2,385 girls) were analyzed. Joint and Individual Variation Explained (JIVE) identified a brain co-development pattern among 221 brain features (i.e., differences in surface area, thickness, or cortical and subcortical gray-matter volume between baseline and two-year-follow-up data). Generalized linear mixed-effect models investigated associations between baseline SMA, structural co-development and internalizing and externalizing psychopathology at two-year follow-up.

Results: SMA at baseline was related to internalizing psychopathology at year 2 (β=0.020,SE=0.008,P=0.014) and a structural co-development pattern (β=0.015,SE=0.007,P=0.029), where the co-development pattern suggested that rates of change in gray-matter volumes of the brainstem, gray-matter volumes and/or cortical thickness measures of bilateral superior frontal, rostral middle frontal, inferior parietal, and inferior temporal regions were more similar than those in other regions. This component partially mediated the relationship between baseline SMA and future internalizing problems (indirect effect = 0.020, P-value = 0.043, proportion mediated: 2.24%).

Discussion and conclusions: Greater youth engagement in SMA at ages 9-10 years statistically predicted higher levels of internalizing two years later. This association was mediated by cortical-brainstem circuitry, albeit with relatively small effect sizes. The findings may help delineate processes contributing to internalizing behaviors and assist in identifying individuals at greater risk for such problems.

Kong R, Tan YR, Wulan N, Ooi LQR, Farahibozorg SR, Harrison S, Bijsterbosch JD, Bernhardt BC, Eickhoff S, Yeo BTT. Comparison Between Gradients and Parcellations for Functional Connectivity Prediction of Behavior. Neuroimage. 2023 Mar 18:120044. doi: 10.1016/j.neuroimage.2023.120044. Epub ahead of print. PMID: 36940760.

Resting-state functional connectivity (RSFC) is widely used to predict behavioral measures. To predict behavioral measures, representing RSFC with parcellations and gradients are the two most popular approaches. Here, we compare parcellation and gradient approaches for RSFC-based prediction of a broad range of behavioral measures in the Human Connectome Project (HCP) and Adolescent Brain Cognitive Development (ABCD) datasets. Among the parcellation approaches, we consider group-average “hard” parcellations (Schaefer et al., 2018), individual-specific “hard” parcellations (Kong et al., 2021a), and an individual-specific “soft” parcellation (spatial independent component analysis with dual regression; Beckmann et al., 2009). For gradient approaches, we consider the well-known principal gradients (Margulies et al., 2016) and the local gradient approach that detects local RSFC changes (Laumann et al., 2015). Across two regression algorithms, individual-specific hard-parcellation performs the best in the HCP dataset, while the principal gradients, spatial independent component analysis and group-average “hard” parcellations exhibit similar performance. On the other hand, principal gradients and all parcellation approaches perform similarly in the ABCD dataset. Across both datasets, local gradients perform the worst. Finally, we find that the principal gradient approach requires at least 40 to 60 gradients to perform as well as parcellation approaches. While most principal gradient studies utilize a single gradient, our results suggest that incorporating higher order gradients can provide significant behaviorally relevant information. Future work will consider the inclusion of additional parcellation and gradient approaches for comparison.

Qiu A, Liu C. Pathways link environmental and genetic factors with structural brain networks and psychopathology in youth. Neuropsychopharmacology. 2023 Mar 17. doi: 10.1038/s41386-023-01559-7. Epub ahead of print. PMID: 36928354.

Adolescence is a period of significant brain development and maturation, and it is a time when many mental health problems first emerge. This study aimed to explore a comprehensive map that describes possible pathways from genetic and environmental risks to structural brain organization and psychopathology in adolescents. We included 32 environmental items on developmental adversity, maternal substance use, parental psychopathology, socioeconomic status (SES), school and family environment; 10 child psychopathological scales; polygenic risk scores (PRS) for 10 psychiatric disorders, total problems, and cognitive ability; and structural brain networks in the Adolescent Brain Cognitive Development study (ABCD, n = 9168). Structural equation modeling found two pathways linking SES, brain, and psychopathology. Lower SES was found to be associated with lower structural connectivity in the posterior default mode network and greater salience structural connectivity, and with more severe psychosis and internalizing in youth (p < 0.001). Prematurity and birth weight were associated with early-developed sensorimotor and subcortical networks (p < 0.001). Increased parental psychopathology, decreased SES and school engagement was related to elevated family conflict, psychosis, and externalizing behaviors in youth (p < 0.001). Increased maternal substance use predicted increased developmental adversity, internalizing, and psychosis (p < 0.001). But, polygenic risks for psychiatric disorders had moderate effects on brain structural connectivity and psychopathology in youth. These findings suggest that a range of genetic and environmental factors can influence brain structural organization and psychopathology during adolescence, and that addressing these risk factors may be important for promoting positive mental health outcomes in young people.

Byington N, Grimsrud G, Mooney MA, et al. Polyneuro risk scores capture widely distributed connectivity patterns of cognition. Developmental Cognitive Neuroscience. Volume 60, April 2023, 101231, https://doi.org/10.1016/j.dcn.2023.101231

Resting-state functional connectivity (RSFC) is a powerful tool for characterizing brain changes, but it has yet to reliably predict higher-order cognition. This may be attributed to small effect sizes of such brain-behavior relationships, which can lead to underpowered, variable results when utilizing typical sample sizes (N∼25). Inspired by techniques in genomics, we implement the polyneuro risk score (PNRS) framework – the application of multivariate techniques to RSFC data and validation in an independent sample. Utilizing the Adolescent Brain Cognitive Development® cohort split into two datasets, we explore the framework’s ability to reliably capture brain-behavior relationships across 3 cognitive scores – general ability, executive function, learning & memory. The weight and significance of each connection is assessed in the first dataset, and a PNRS is calculated for each participant in the second. Results support the PNRS framework as a suitable methodology to inspect the distribution of connections contributing towards behavior, with explained variance ranging from 1.0 % to 21.4 %. For the outcomes assessed, the framework reveals globally distributed, rather than localized, patterns of predictive connections. Larger samples are likely necessary to systematically identify the specific connections contributing towards complex outcomes. The PNRS framework could be applied translationally to identify neurologically distinct subtypes of neurodevelopmental disorders.

Mooney MA, Ryabinin P, Morton H, Selah K, Gonoud R, Kozlowski M, Nousen E, Tipsord J, Antovich D, Schwartz J, Herting MM, Faraone SV, Nigg JT. Joint polygenic and environmental risks for childhood attention-deficit/hyperactivity disorder (ADHD) and ADHD symptom dimensions. JCPP Adv. 2023 Mar 16;3(2):e12152. doi: 10.1002/jcv2.12152. PMID: 37753156; PMCID: PMC10519744.

Background: attention-deficit/hyperactivity disorder (ADHD) is associated with both polygenic liability and environmental exposures, both intrinsic to the family, such as family conflict, and extrinsic, such as air pollution. However, much less is known about the interplay between environmental and genetic risks relevant to ADHD-a better understanding of which could inform both mechanistic models and clinical prediction algorithms.

Methods: Two independent data sets, the population-based Adolescent Brain Cognitive Development Study (ABCD) (N = 11,876) and the case-control Oregon-ADHD-1000 (N = 1449), were used to examine additive (G + E) and interactive (GxE) effects of selected polygenic risk scores (PRS) and environmental factors in a cross-sectional design. Genetic risk was measured using PRS for nine mental health disorders/traits. Exposures included family income, family conflict/negative sentiment, and geocoded measures of area deprivation, lead exposure risk, and air pollution exposure (nitrogen dioxide and fine particulate matter).

Results: ADHD PRS and family conflict jointly predicted concurrent ADHD symptoms in both cohorts. Additive-effects models, including both genetic and environmental factors, explained significantly more variation in symptoms than any individual factor alone (joint R 2 = .091 for total symptoms in ABCD; joint R 2 = .173 in Oregon-ADHD-1000; all delta-R 2 p-values <2e-7). Significant effect size heterogeneity across ancestry groups was observed for genetic and environmental factors (e.g., Q = 9.01, p = .011 for major depressive disorder PRS; Q = 13.34, p = .001 for area deprivation). GxE interactions observed in the full ABCD cohort suggested stronger environmental effects when genetic risk is low, though they did not replicate.

Conclusions: Reproducible additive effects of PRS and family environment on ADHD symptoms were found, but GxE interaction effects were not replicated and appeared confounded by ancestry. Results highlight the potential value of combining exposures and PRS in clinical prediction algorithms. The observed differences in risks across ancestry groups warrant further study to avoid health care disparities.

Dehestani N, Whittle S, Vijayakumar N, Silk TJ. Developmental brain changes during puberty and associations with mental health problems. Developmental Cognitive Neuroscience, Volume 60, April 2023, 101227. https://doi.org/10.1016/j.dcn.2023.101227

Background
Our understanding of the mechanisms relating pubertal timing to mental health problems via brain development remains rudimentary.

Method
Longitudinal data was sourced from ∼11,500 children from the Adolescent Brain Cognitive Development (ABCD) Study (age 9–13years). We built models of “brain age” and “puberty age” as indices of brain and pubertal development. Residuals from these models were used to index individual differences in brain development and pubertal timing, respectively. Mixed-effects models were used to investigate associations between pubertal timing and regional and global brain development. Mediation models were used to investigate the indirect effect of pubertal timing on mental health problems via brain development.

Results
Earlier pubertal timing was associated with accelerated brain development, particularly of subcortical and frontal regions in females and subcortical regions in males. While earlier pubertal timing was associated with elevated mental health problems in both sexes, brain age did not predict mental health problems, nor did it mediate associations between pubertal timing and mental health problems.

Conclusion
This study highlights the importance of pubertal timing as a marker associated with brain maturation and mental health problems.

Ryan JE, McCabe SE, DiDonato S, Boyd CJ, Voepel-Lewis T, Ploutz-Snyder RJ, Veliz P. Racial/ethnic disparities in mental healthcare in youth with incarcerated parents. Am J Prev Med. 2023 Mar 12:S0749-3797(23)00133-2. doi: 10.1016/j.amepre.2023.03.008. Epub ahead of print. PMID: 36918134.

Introduction: Youth with incarcerated parents (YIP) experience more Adverse Childhood Experiences (ACEs) than other youth, placing them at higher risk for mental health and substance use disorders. Despite their increased risk, these youth may be less likely to access mental health services, particularly given their racial and ethnic makeup. Therefore, this study aimed to assess racial and ethnic disparities in access to mental health services for YIP.

Methods: This secondary data analysis used longitudinal data from 2016 to 2019 from the Adolescent Brain Cognitive Development Study. Logistic regression models assessed the relationships among incarceration, cumulative ACEs, DSM-5 diagnoses and mental health services. Additional analyses stratified these models by race and ethnicity. All analyses were performed in 2022.

Results: YIP were more likely to report 4 or more ACEs (51% vs 14%, aOR 3.92, 95% CI 3.3-4.65, p <0.001) and to have received mental health services (25% vs 15%, 1.89 aOR, 1.6-2.21, p<0.001) compared to unexposed youth. However, Black YIP (19% vs 34%, aOR 0.38, 95% CI .27-.52, p<0.001) and Latinx YIP (10% vs 17%, aOR 0.5, 95% CI .33-.76, p<0.001) were significantly less likely to report receiving mental health services compared to White YIP and non-Latinx YIP, respectively.

Conclusions: YIP were more likely to report utilization of mental health services, but significant racial and ethnic disparities exist between Black and Latinx YIP compared to White and non-Latinx YIP. There is a continued need to expand mental health services to YIP and to address racial and ethnic disparities in access to care.

Ou YN, Wu BS, Ge YJ, Zhang Y, Jiang YC, Kuo K, Yang L, Tan L, Feng JF, Cheng W, Yu JT. The genetic architecture of human amygdala volumes and their overlap with common brain disorders. Transl Psychiatry. 2023 Mar 11;13(1):90. doi: 10.1038/s41398-023-02387-5. PMID: 36906575; PMCID: PMC10008562.

The amygdala is a crucial interconnecting structure in the brain that performs several regulatory functions, yet its genetic architectures and involvement in brain disorders remain largely unknown. We carried out the first multivariate genome-wide association study (GWAS) of amygdala subfield volumes in 27,866 UK Biobank individuals. The whole amygdala was segmented into nine nuclei groups using Bayesian amygdala segmentation. The post-GWAS analysis allowed us to identify causal genetic variants in phenotypes at the SNP, locus, and gene levels, as well as genetic overlap with brain health-related traits. We further generalized our GWAS in Adolescent Brain Cognitive Development (ABCD) cohort. The multivariate GWAS identified 98 independent significant variants within 32 genomic loci associated (P < 5 × 10-8) with amygdala volume and its nine nuclei. The univariate GWAS identified significant hits for eight of the ten volumes, tagging 14 independent genomic loci. Overall, 13 of the 14 loci identified in the univariate GWAS were replicated in the multivariate GWAS. The generalization in ABCD cohort supported the GWAS results with the 12q23.2 (RNA gene RP11-210L7.1) being discovered. All of these imaging phenotypes are heritable, with heritability ranging from 15% to 27%. Gene-based analyses revealed pathways relating to cell differentiation/development and ion transporter/homeostasis, with the astrocytes found to be significantly enriched. Pleiotropy analyses revealed shared variants with neurological and psychiatric disorders under the conjFDR threshold of 0.05. These findings advance our understanding of the complex genetic architectures of amygdala and their relevance in neurological and psychiatric disorders.

Loso H, Chaarani B, Dube SL, Albaugh MD, Cheaito A, Garavan H, Potter A. Gender diversity associated with patterns of brain activation seen in populations that experience childhood stress. Front Integr Neurosci. 2023 Mar 9;17:1084748. doi: 10.3389/fnint.2023.1084748. PMID: 36969492; PMCID: PMC10033574.

Introduction: Stressful childhood experiences are associated with unique brain activity patterns during emotional processing. Specifically, pediatric stress is linked to activation in the insulae, superior temporal and parahippocampal gyri, and the amygdalae, as well as differential activation in the dorsal anterior cingulate cortex when viewing emotional faces. Gender diversity is broadly associated with higher victimization and mental health disparities in children aged 9/10, but whether it is associated with stress-like alterations in brain function (BOLD signal during task-based fMRI) remains unknown. We investigate the functional brain correlates of this relationship to determine if gender-diverse youth show patterns of functional activity during an emotional task consistent with those of other populations that experience heightened stress.

Methods: We used data from the Adolescent Brain Cognitive Development (ABCD)® study. First, we identified a subset of 4,385 participants aged 10/11 years with gender diversity data and quality-controlled fMRI data from the EN-Back (emotional n-back) task. The EN-Back is a working memory task that presents emotion faces as well as pictures of places as control stimuli. We regressed BOLD signal associated with emotion faces (faces minus places contrast) on gender diversity. Next, we tested if parental acceptance or youth perceptions of their school environment moderated the relationship between gender diversity and activation in the insulae or fusiform gyrus. Finally, we used structural equation modeling to investigate gender diversity’s association with parental acceptance, perceptions of school environments, internalizing and externalizing problems.

Results: Gender diversity was associated with widespread increases in BOLD signal during the faces condition of the EN-Back task. Youth’s report of parental acceptance and school environment did not moderate the relationship between gender diversity and BOLD signal in the insula or fusiform gyrus. Gender diversity was related to greater parent and school-related stress, which was associated with elevated mental health problems.

Conclusion: Patterns of functional activity were consistent with those reported in prior literature on childhood stress. Gender diversity was associated with increased emotional and behavioral problems, as well as parent and school-related stress. These findings indicate the importance of the home and school environments for supporting the wellbeing of gender diverse youth.

Tervo-Clemmens, B., Marek, S., Chauvin, R.J. et al. Reply to: Multivariate BWAS can be replicable with moderate sample sizes. Nature 615, E8–E12 (2023). https://doi.org/10.1038/s41586-023-05746-w

REPLYING TO: T. Spisak et al. Nature https://doi.org/10.1038/s41586-023-05745-x (2023)

Spisak, T., Bingel, U. & Wager, T.D. Multivariate BWAS can be replicable with moderate sample sizes. Nature 615, E4–E7 (2023). https://doi.org/10.1038/s41586-023-05745-x

ARISING FROM: S. Marek et al. Reproducible brain-wide association studies require thousands of individuals. Nature https://doi.org/10.1038/s41586-022-04492-9 (2022)

Nagata JM, Smith N, Zamora G, Sajjad OM, Ganson KT, Testa A, Jackson DB. Problematic social media use and alcohol expectancies in early adolescents. BMC Public Health. 2023 Mar 6;23(1):430. doi: 10.1186/s12889-023-15298-3. PMID: 36879232.

Background: Alcohol expectancies are beliefs regarding positive (e.g., tension reduction) or negative (e.g., loss of motor coordination) effects of alcohol. Based on Social Learning Theory, social media can influence alcohol expectancies in adolescents. In particular, problematic social media use – which can reflect elements of addiction, including mood modification, tolerance, withdrawal, conflict, and relapse – could be linked to alcohol expectancies. We aimed to determine the associations between problematic social media use and alcohol expectancies in a national (U.S.) cohort of 10-14-year-old early adolescents.

Methods: We analyzed cross-sectional data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 9,008) at the Year 2 assessment (2018-2020). Unadjusted and adjusted linear regression analyses were conducted to examine the associations between problematic social media use and alcohol expectancies (positive and negative), adjusting for race/ethnicity, sex, household income, parent education, sexual orientation, parental marital status, and study site. Furthermore, we computed marginal predicted probabilities to aid in interpreting findings.

Results: The sample was 48.7% female and racially and ethnically diverse (43.0% non-White), with a mean age of 12.02 ± 0.66 years old. In models adjusted for confounders including both time spent on social media and problematic social media use, time spent on social media was not associated with positive or negative alcohol expectancies, but higher problematic social media use score was associated with higher positive (B = 0.045, 95% confidence interval [CI] 0.020-0.069) and negative (B = 0.072, 95% CI 0.043-0.101) alcohol expectancies scores.

Conclusion: Problematic social media use was associated with both positive and negative alcohol expectancies in a demographically diverse national sample of early adolescents in the U.S. Given the small effect sizes of the current study, future studies should further examine these relationships prospectively, as well as the mechanisms linking problematic social media use to alcohol expectancies and alcohol consumption. Because alcohol expectancies are modifiable and linked with alcohol initiation, they could be a target for future prevention efforts.

Hehr A, Huntley ED, Marusak HA. Getting a Good Night’s Sleep: Associations Between Sleep Duration and Parent-Reported Sleep Quality on Default Mode Network Connectivity in Youth. J Adolesc Health. 2023 Mar 3:S1054-139X(23)00057-5. doi: 10.1016/j.jadohealth.2023.01.010. Epub ahead of print. PMID: 36872118.

Purpose: Sleep plays an important role in healthy neurocognitive development, and poor sleep is linked to cognitive and emotional dysfunction. Studies in adults suggest that shorter sleep duration and poor sleep quality may disrupt core neurocognitive networks, particularly the default mode network (DMN)-a network implicated in internal cognitive processing and rumination. Here, we examine the relationships between sleep and within- and between-network resting-state functional connectivity (rs-FC) of the DMN in youth.

Methods: This study included 3,798 youth (11.9 ± 0.6 years, 47.5% female) from the Adolescent Brain Cognitive Development cohort. Sleep duration and wake after sleep onset (WASO) were quantified using Fitbit watch recordings, and parent-reported sleep disturbances were measured using the Sleep Disturbance Scale for Children. We focused on rs-FC between the DMN and anticorrelated networks (i.e., dorsal attention network [DAN], frontoparietal network, salience network).

Results: Both shorter sleep duration and greater sleep disturbances were associated with weaker within-network DMN rs-FC. Shorter sleep duration was also associated with weaker anticorrelation (i.e., higher rs-FC) between the DMN and two anticorrelated networks: the DAN and frontoparietal network. Greater WASO was also associated with DMN-DAN rs-FC, and the effects of WASO on rs-FC were most pronounced among children who slept fewer hours/night.

Discussion: Together, these data suggest that different aspects of sleep are associated with distinct and interactive alterations in resting-state brain networks. Alterations in core neurocognitive networks may confer increased risk for emotional psychopathology and attention-related vulnerabilities. Our findings contribute to the growing number of studies demonstrating the importance of healthy sleep practices in youth.

Kopal, J., Uddin, L.Q. & Bzdok, D. The end game: respecting major sources of population diversity. Nat Methods (2023). https://doi.org/10.1038/s41592-023-01812-3

Human neuroscience is enjoying burgeoning population data resources: large-scale cohorts with thousands of participant profiles of gene expression, brain scanning and sociodemographic measures. The depth of phenotyping puts us in a better position than ever to fully embrace major sources of population diversity as effects of interest to illuminate mechanisms underlying brain health.

Diversity in population cohorts: the elephant(s) in the room?
The neurosciences have now entered the era of big data, aggregating measurements from ever more sites and countries. Openly shared data repositories of human brain structure, connectivity or task responses, as well as participants’ genetics, environment and lifestyle, pave the way for tackling new research questions and developing new analytical methods1,2. The UK Biobank, the world’s largest biomedical dataset, collates deep genetic, brain and phenomic data from ~500,000 individuals. Its measurements also cover cognitive function, medical history, sociodemographic data, or lifestyle and physical measures3. In addition, there are large-scale initiatives such as the Human Connectome Project, the Adolescent Brain Cognitive Development (ABCD) Study, the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium and the Healthy Brain Network. However, using these emerging large datasets does not provide a free ticket to neuroscience insights or clinical translation of predictive models.

Here we argue that placing a premium on population diversity has the potential to reveal untapped and more reproducible insights into the human brain. Today, we are in a better position than ever to fully attend to major sources of population stratification that are routinely inaccessible in smaller datasets, cohorts or initiatives.

Nagata JM, Smith N, Sajjid OM, Zamora G, Raney JH, Ganson KT, Testa A, Vittinghoff E, Jackson DB. Adverse Childhood Experiences and Sipping Alcohol in U.S. Children: Findings from the Adolescent Brain Cognitive Development Study. Preventive Medicine Reports, Volume 32, April 2023, 102153, https://doi.org/10.1016/j.pmedr.2023.102153

The objective of this study was to explore the relationship between accumulating adverse childhood experiences (ACEs) and sipping alcohol in a large, nationwide sample of 9-to-10-year-old U.S. children. We analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study (2016–2018). Of 10,853 children (49.1 % female), 23.4 % reported ever sipping alcohol. A greater ACE score was associated with a higher risk of sipping alcohol. Having 4 or more ACEs placed children at 1.27 times the risk (95 % CI 1.11–1.45) of sipping alcohol compared to children with no ACEs. Among the nine distinct ACEs examined, household violence (Risk Ratio [RR] = 1.13, 95 % CI 1.04–1.22) and household alcohol abuse (RR = 1.14, 95 % CI 1.05–1.22) were associated with sipping alcohol during childhood. Our findings indicate a need for increased clinical attention to alcohol sipping among ACE-exposed children.

MacSweeney N, Allardyce J, Edmondson-Stait A, Shen X, Casey H, Chan SWY, Cullen B, Reynolds RM, Frangou S, Kwong ASF, Lawrie SM, Romaniuk L, Whalley HC. The role of brain structure in the association between pubertal timing and depression risk in an early adolescent sample (the ABCD Study®): A registered report. Developmental Cognitive Neuroscience, Volume 60, April 2023, 101223, https://doi.org/10.1016/j.dcn.2023.101223

Background
Earlier pubertal timing is associated with higher rates of depressive disorders in adolescence. Neuroimaging studies report brain structural associations with both pubertal timing and depression. However, whether brain structure mediates the relationship between pubertal timing and depression remains unclear.

Methods
The current registered report examined associations between pubertal timing (indexed via perceived pubertal development), brain structure (cortical and subcortical metrics, and white matter microstructure) and depressive symptoms in a large sample (N = ∼5000) of adolescents (aged 9–13 years) from the Adolescent Brain Cognitive Development (ABCD) Study. We used three waves of follow-up data when the youth were aged 10–11 years, 11–12 years, and 12–13 years, respectively. We used generalised linear-mixed models (H1) and structural equation modelling (H2 & H3) to test our hypotheses.

Hypotheses
We hypothesised that earlier pubertal timing at Year 1 would be associated with increased depressive symptoms at Year 3 (H1), and that this relationship would be mediated by global (H2a-b) and regional (H3a-g) brain structural measures at Year 2. Global measures included reduced cortical volume, thickness, surface area and sulcal depth. Regional measures included reduced cortical thickness and volume in temporal and fronto-parietal areas, increased cortical volume in the ventral diencephalon, increased sulcal depth in the pars orbitalis, and reduced fractional anisotropy in the cortico-striatal tract and corpus callosum. These regions of interest were informed by our pilot analyses using baseline ABCD data when the youth were aged 9–10 years.

Results
Earlier pubertal timing was associated with increased depressive symptoms two years later. The magnitude of effect was stronger in female youth and the association remained significant when controlling for parental depression, family income, and BMI in females but not in male youth. Our hypothesised brain structural measures did not however mediate the association between earlier pubertal timing and later depressive symptoms.

Conclusion
The present results demonstrate that youth, particularly females, who begin puberty ahead of their peers are at an increased risk for adolescent-onset depression. Future work should explore additional biological and socio-environmental factors that may affect this association so that we can identify targets for intervention to help these at-risk youth.

Kim WP, Kim HJ, Pack SP, Lim JH, Cho CH, Lee HJ. Machine Learning-Based Prediction of Attention-Deficit/Hyperactivity Disorder and Sleep Problems With Wearable Data in Children. JAMA Netw Open. 2023 Mar 1;6(3):e233502. doi: 10.1001/jamanetworkopen.2023.3502. PMID: 36930149; PMCID: PMC10024208.

Importance: Early detection of attention-deficit/hyperactivity disorder (ADHD) and sleep problems is paramount for children’s mental health. Interview-based diagnostic approaches have drawbacks, necessitating the development of an evaluation method that uses digital phenotypes in daily life.

Objective: To evaluate the predictive performance of machine learning (ML) models by setting the data obtained from personal digital devices comprising training features (ie, wearable data) and diagnostic results of ADHD and sleep problems by the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version for Diagnostic and Statistical Manual of Mental Disorders, 5th edition (K-SADS) as a prediction class from the Adolescent Brain Cognitive Development (ABCD) study.

Design, setting, and participants: In this diagnostic study, wearable data and K-SADS data were collected at 21 sites in the US in the ABCD study (release 3.0, November 2, 2020, analyzed October 11, 2021). Screening data from 6571 patients and 21 days of wearable data from 5725 patients collected at the 2-year follow-up were used, and circadian rhythm-based features were generated for each participant. A total of 12 348 wearable data for ADHD and 39 160 for sleep problems were merged for developing ML models.

Main outcomes and measures: The average performance of the ML models was measured using an area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In addition, the Shapley Additive Explanations value was used to calculate the importance of features.

Results: The final population consisted of 79 children with ADHD problems (mean [SD] age, 144.5 [8.1] months; 55 [69.6%] males) vs 1011 controls and 68 with sleep problems (mean [SD] age, 143.5 [7.5] months; 38 [55.9%] males) vs 3346 controls. The ML models showed reasonable predictive performance for ADHD (AUC, 0.798; sensitivity, 0.756; specificity, 0.716; PPV, 0.159; and NPV, 0.976) and sleep problems (AUC, 0.737; sensitivity, 0.743; specificity, 0.632; PPV, 0.036; and NPV, 0.992).

Conclusions and relevance: In this diagnostic study, an ML method for early detection or screening using digital phenotypes in children’s daily lives was developed. The results support facilitating early detection in children; however, additional follow-up studies can improve its performance.

Xiao Y, Brown TT, Snowden LR, Chow JC, Mann JJ. COVID-19 Policies, Pandemic Disruptions, and Changes in Child Mental Health and Sleep in the United States. JAMA Netw Open. 2023 Mar 1;6(3):e232716. doi: 10.1001/jamanetworkopen.2023.2716. PMID: 36912834.

Importance: The adverse effects of COVID-19 containment policies disrupting child mental health and sleep have been debated. However, few current estimates correct biases of these potential effects.

Objectives: To determine whether financial and school disruptions related to COVID-19 containment policies and unemployment rates were separately associated with perceived stress, sadness, positive affect, COVID-19-related worry, and sleep.

Design, setting, and participants: This cohort study was based on the Adolescent Brain Cognitive Development Study COVID-19 Rapid Response Release and used data collected 5 times between May and December 2020. Indexes of state-level COVID-19 policies (restrictive, supportive) and county-level unemployment rates were used to plausibly address confounding biases through 2-stage limited information maximum likelihood instrumental variables analyses. Data from 6030 US children aged 10 to 13 years were included. Data analysis was conducted from May 2021 to January 2023.

Exposures: Policy-induced financial disruptions (lost wages or work due to COVID-19 economic impact); policy-induced school disruptions (switches to online or partial in-person schooling).

Main outcomes and measures: Perceived stress scale, National Institutes of Health (NIH)-Toolbox sadness, NIH-Toolbox positive affect, COVID-19-related worry, and sleep (latency, inertia, duration).

Results: In this study, 6030 children were included in the mental health sample (weighted median [IQR] age, 13 [12-13] years; 2947 [48.9%] females, 273 [4.5%] Asian children, 461 [7.6%] Black children, 1167 [19.4%] Hispanic children, 3783 [62.7%] White children, 347 [5.7%] children of other or multiracial ethnicity). After imputing missing data, experiencing financial disruption was associated with a 205.2% [95% CI, 52.9%-509.0%] increase in stress, a 112.1% [95% CI, 22.2%-268.1%] increase in sadness, 32.9% [95% CI, 3.5%-53.4%] decrease in positive affect, and a 73.9 [95% CI, 13.2-134.7] percentage-point increase in moderate-to-extreme COVID-19-related worry. There was no association between school disruption and mental health. Neither school disruption nor financial disruption were associated with sleep.

Conclusions and relevance: To our knowledge, this study presents the first bias-corrected estimates linking COVID-19 policy-related financial disruptions with child mental health outcomes. School disruptions did not affect indices of children’s mental health. These findings suggest public policy should consider the economic impact on families due to pandemic containment measures, in part to protect child mental health until vaccines and antiviral drugs become available.

Kim EH, Jenness JL, Miller AB, Halabi R, de Zambotti M, Bagot KS, Baker FC, Pratap A. Association of Demographic and Socioeconomic Indicators With the Use of Wearable Devices Among Children. JAMA Netw Open. 2023 Mar 1;6(3):e235681. doi: 10.1001/jamanetworkopen.2023.5681. PMID: 36995714.

Importance: The use of consumer-grade wearable devices for collecting data for biomedical research may be associated with social determinants of health (SDoHs) linked to people’s understanding of and willingness to join and remain engaged in remote health studies.

Objective: To examine whether demographic and socioeconomic indicators are associated with willingness to join a wearable device study and adherence to wearable data collection in children.

Design, setting, and participants: This cohort study used wearable device usage data collected from 10 414 participants (aged 11-13 years) at the year-2 follow-up (2018-2020) of the ongoing Adolescent Brain and Cognitive Development (ABCD) Study, performed at 21 sites across the United States. Data were analyzed from November 2021 to July 2022.

Main outcomes and measures: The 2 primary outcomes were (1) participant retention in the wearable device substudy and (2) total device wear time during the 21-day observation period. Associations between the primary end points and sociodemographic and economic indicators were examined.

Results: The mean (SD) age of the 10 414 participants was 12.00 (0.72) years, with 5444 (52.3%) male participants. Overall, 1424 participants (13.7%) were Black; 2048 (19.7%), Hispanic; and 5615 (53.9%) White. Substantial differences were observed between the cohort that participated and shared wearable device data (wearable device cohort [WDC]; 7424 participants [71.3%]) compared with those who did not participate or share data (no wearable device cohort [NWDC]; 2900 participants [28.7%]). Black children were significantly underrepresented (-59%) in the WDC (847 [11.4%]) compared with the NWDC (577 [19.3%]; P < .001). In contrast, White children were overrepresented (+132%) in the WDC (4301 [57.9%]) vs the NWDC (1314 [43.9%]; P < .001). Children from low-income households (<$24 999) were significantly underrepresented in WDC (638 [8.6%]) compared with NWDC (492 [16.5%]; P < .001). Overall, Black children were retained for a substantially shorter duration (16 days; 95% CI, 14-17 days) compared with White children (21 days; 95% CI, 21-21 days; P < .001) in the wearable device substudy. In addition, total device wear time during the observation was notably different between Black vs White children (β = -43.00 hours; 95% CI, -55.11 to -30.88 hours; P < .001).

Conclusions and relevance: In this cohort study, large-scale wearable device data collected from children showed considerable differences between White and Black children in terms of enrollment and daily wear time. While wearable devices provide an opportunity for real-time, high-frequency contextual monitoring of individuals’ health, future studies should account for and address considerable representational bias in wearable data collection associated with demographic and SDoH factors.

Ford SH, Bruckner L, Thoyre S, Baker MJ, Bartlett TR, Hodges EA. Gut-Brain Axis Perspective on Negative Symptoms and Their Neighbors in Early Adolescence: Can We Move Care Upstream? J Psychosoc Nurs Ment Health Serv. 2023 Mar 5:1-10. doi: 10.3928/02793695-20230221-03. Epub ahead of print. PMID: 36853039.

The current study investigated symptom network patterns in adolescents from a gut-brain-axis (GBA) biopsychosocial perspective. Our secondary analysis of data from the Adolescent Brain Cognitive Development Study assessed symptom relationships using network analysis to provide information about multivariate structural dependencies among 41 signs and symptoms. Cross-sectional EBICglasso symptom networks were evaluated to assess patterns associated with anhedonia and depressed mood. Significant differences were identified between symptom neighbors of anhedonia compared with depressed mood based on stratification by age. The GBA perspective revealed several symptom neighbors that could expand clinical assessment, diagnosing criteria, education, and interventions for adolescents at risk for, or with, anhedonia or depressed mood. Results speak to the unique impact of symptoms on health that are not interchangeable with other symptoms and do not have equal effects. Mental health nurses should consider a holistic and proactive precision health approach to improving health and well-being through evidence-based assessment of symptom associations.

Fung H, Yeo BTT, Chen C, Lo JC, Chee MWL, Ong JL. Adherence to 24-Hour Movement Recommendations and Health Indicators in Early Adolescence: Cross-Sectional and Longitudinal Associations in the Adolescent Brain Cognitive Development Study. J Adolesc Health. 2023 Mar;72(3):460-470. doi: 10.1016/j.jadohealth.2022.10.019. Epub 2022 Dec 15. PMID: 36528521.

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

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

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

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

Dégeilh F, von Soest T, Ferschmann L, Beer JC, Gaubert M, Koerte IK, Tamnes CK. Social problems and brain structure development following childhood mild traumatic brain injury. Cortex. 2023 Feb 27;162:26-37. doi: 10.1016/j.cortex.2023.02.003. Epub ahead of print. PMID: 36965337.

Childhood mild traumatic brain injury (mTBI) is associated with elevated risk of developing social problems, which may be underpinned by changes in the structural developmental trajectory of the social brain, a network of cortical regions supporting social cognition and behavior. However, limited sample sizes and cross-sectional designs generally used in neuroimaging studies of pediatric TBI have prevented explorations of this hypothesis. This longitudinal retrospective study examined the development of parent-reported social problems and cortical thickness in social brain regions following childhood mTBI using data from the large population-based Adolescent Brain Cognitive Development (ABCD) Study. Two-group latent change score models revealed different developmental trajectories from ages 10-12 years in the level of social problems between children with (n = 345) and without (n = 7,089) mTBI. Children with mTBI showed higher, but non-clinical, levels of social problems than controls at age 10. Then, social problems decreased over 2 years, but still remained higher, but non-clinical, than in controls in which they stayed stable. Both groups showed similar decreases in social brain cortical thickness between ages 10 and 12 years. Further studies providing detailed information on the injury mechanism and acute symptoms are needed to better understand individual differences in social functioning and brain development in pediatric TBI.

Spechler PA, Gutierrez RM, Tapert SF, Thompson WK, Paulus MP. The beneficial effect of sleep on behavioral health problems in youth is disrupted by prenatal cannabis exposure: A causal random forest analysis of Adolescent Brain Cognitive Development data. Child Dev. 2023 Feb 24. doi: 10.1111/cdev.13899. Epub ahead of print. PMID: 36840387.

Studies suggest prenatal cannabis exposure is associated with mood/behavioral problems in children. However, it is unclear if targeting modifiable domains like sleep behaviors would improve outcomes in exposed youth. Using a causal inference framework, the effect of changing sleep-hours on changing internalizing/externalizing problems in children was examined using the Adolescent Brain Cognitive Development™ study baseline (ages 9-10; collected during 2016-2018) and year-1 follow-up data (N = 9825; 4663 female; 5196 white). Average treatment effects (ATE) indicated that more sleep predicted less internalizing (ATE = -.34, SE = .08, p < .001) and externalizing (ATE = -.29, SE = .07, p < .001) problems over time. However, prenatal cannabis exposure moderated the ATE on internalizing (conditional-ATE = .91, SE = .39, p = .019), whereby participants with exposure (n = 605) did not show any effect of changing sleep-hours on mood (B = .09, SE = .24).

Hiraoka D, Makita K, Hamatani S, Tomoda A, Mizuno Y. Effects of prenatal cannabis exposure on developmental trajectory of cognitive ability and brain volumes in the adolescent brain cognitive development (ABCD) study. Dev Cogn Neurosci. 2023 Feb 6;60:101209. doi: 10.1016/j.dcn.2023.101209. Epub ahead of print. PMID: 36791556.

Although cannabis use during pregnancy is increasing widely, the effects of cannabis on developmental trajectories, such as whether its effects during pregnancy remain the same between time points or gradually increase, are unclear. This study aimed to examine whether cannabis use during pregnancy affects the process of change in cognition and brain volume. Data from two-time points measured longitudinally were analyzed. We used data from the Adolescent Brain and Cognitive Development Study. Participants included 11,876 children aged 9–11 years participated at baseline, and 10,414 participated at 2-year follow-up from 22 sites across the United States. We explored the associations between prenatal cannabis exposure and cognitive abilities and brain volumes developmental trajectories. Among 11,530 children with valid data for prenatal cannabis exposure, 10,833 had no prenatal cannabis use, and 697 had cannabis use during their pregnancy. There was a significant interaction between time points and cannabis use during pregnancy on visuo-perceptual processing ability (b = −0.019, p = .009) and intracranial volumes (b = −6338.309, p = .009). We found that the effects of exposure to cannabis during pregnancy are not uniform at all times and may gradually become more apparent and magnified as development progresses.

Holm MC, Leonardsen EH, Beck D, Dahl A, Kjelkenes R, de Lange AG, Westlye LT. Linking brain maturation and puberty during early adolescence using longitudinal brain age prediction in the ABCD cohort. Dev Cogn Neurosci. 2023 Feb 22;60:101220. doi: 10.1016/j.dcn.2023.101220. Epub ahead of print. PMID: 36841180.

The temporal characteristics of adolescent neurodevelopment are shaped by a complex interplay of genetic, biological, and environmental factors. Using a large longitudinal dataset of children aged 9-13 from the Adolescent Brain Cognitive Development (ABCD) study we tested the associations between pubertal status and brain maturation. Brain maturation was assessed using brain age prediction based on convolutional neural networks and minimally processed T1-weighted structural MRI data. Brain age prediction provided highly accurate and reliable estimates of individual age, with an overall mean absolute error of 0.7 and 1.4 years at the two timepoints respectively, and an intraclass correlation of 0.65. Linear mixed effects (LME) models accounting for age and sex showed that on average, a one unit increase in pubertal maturational level was associated with a 2.22 months higher brain age across time points (β = 0.10, p < .001). Moreover, annualized change in pubertal development was weakly related to the rate of change in brain age (β = .047, p = 0.04). These results demonstrate a link between sexual development and brain maturation in early adolescence, and provides a basis for further investigations of the complex sociobiological impacts of puberty on life outcomes.

Jessel CD, Narang A, Zuberi R, Bousman CA. Sleep Quality and Duration in Children That Consume Caffeine: Impact of Dose and Genetic Variation in ADORA2A and CYP1A. Genes (Basel). 2023 Jan 22;14(2):289. doi: 10.3390/genes14020289. PMID: 36833216; PMCID: PMC9956387.

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

Tomasi D, Volkow ND. Measures of Brain Connectivity and Cognition by Sex in US Children. JAMA Netw Open. 2023;6(2):e230157. doi:10.1001/jamanetworkopen.2023.0157

Importance
The neurobiological underpinnings underlying sex differences in cognition during adolescence are largely unknown.

Objective
To examine sex differences in brain circuitry and their association with cognitive performance in US children.

Design, Setting, and Participants
This cross-sectional study analyzed behavioral and imaging data from 9- to 11-year-old children from the Adolescent Brain Cognitive Development (ABCD) study between August 2017 and November 2018. The ABCD study is an open-science, multisite study following up more than 11 800 youths into early adulthood for 10 years with annual laboratory-based assessments and biennial magnetic resonance imaging (MRI). The selection of ABCD study children for the current analysis was based on the availability of functional and structural MRI data sets in ABCD Brain Imaging Data Structure Community Collection format. Five hundred and sixty participants who had excessive level of head motion (>50% of time points with framewise displacement >0.5 mm) during resting-state functional MRI were excluded from the analyses. Data were analyzed between January and August 2022.

Main Outcomes and Measures
The main outcomes were the sex differences in (A) global functional connectivity density at rest and (B) mean water diffusivity (MD) and (C) the correlation of these metrics with total cognitive scores.

Results
A total of 8961 children (4604 boys and 4357 girls; mean [SD] age, 9.92 [0.62] years) were included in this analysis. Girls had higher functional connectivity density in default mode network hubs than boys, predominantly in the posterior cingulate cortex (Cohen d = −0.36), and lower MD and transverse diffusivity, predominantly in the superior corticostriatal white matter bundle (Cohen d = 0.3). Age-corrected fluid and total composite scores were higher for girls than for boys (Cohen d = −0.08 [fluid] and −0.04 [total]; P = 2.7 × 10−5). Although total mean (SD) brain volume (1260 [104] mL in boys and 1160 [95] mL in girls; t = 50; Cohen d = 1.0; df = 8738) and the proportion of white matter (d = 0.4) were larger for boys than for girls, the proportion of gray matter was larger for girls than for boys (d = −0.3; P = 2.2 × 10−16).

Conclusions and Relevance
The findings of this cross-sectional study on sex differences in brain connectivity and cognition are relevant to the future creation of brain developmental trajectory charts to monitor for deviations associated with impairments in cognition or behavior, including those due to psychiatric or neurological disorders. They could also serve as a framework for studies investigating the differential contribution of biological vs social or cultural factors in the neurodevelopmental trajectories of girls and boys.

Bakoyiannis, I. Genetic risk for obesity impacts the brain and behavior in youth. Nat. Mental Health 1, 82 (2023). https://doi.org/10.1038/s44220-023-00020-4

Obesity pandemic is reaching an alarming level globally, including in childhood, with a strong tendency to carry it over in adulthood. Obesity induces deleterious neurobiological outcomes; however, Morys et al. investigated how genetic predisposition to obesity — not obesity itself — impacts the brain and behavior. “We focused on children, as the effects of chronic obesity on the brain are possibly low, so any brain changes associated with genetic risk for obesity would likely constitute vulnerability factors rather than secondary effects of obesity,” explains Filip Morys, the first author of the study.

Zhao W, Makowski C, Hagler DJ, Garavan HP, Thompson WK, Greene DJ, Jernigan TL, Dale AM. Task fMRI paradigms may capture more behaviorally relevant information than resting-state functional connectivity. Neuroimage. 2023 Feb 17;270:119946. doi: 10.1016/j.neuroimage.2023.119946. Epub ahead of print. PMID: 36801369.

Characterizing the optimal fMRI paradigms for detecting behaviorally relevant functional connectivity (FC) patterns is a critical step to furthering our knowledge of the neural basis of behavior. Previous studies suggested that FC patterns derived from task fMRI paradigms, which we refer to as task-based FC, are better correlated with individual differences in behavior than resting-state FC, but the consistency and generalizability of this advantage across task conditions was not fully explored. Using data from resting-state fMRI and three fMRI tasks from the Adolescent Brain Cognitive Development Study ® (ABCD), we tested whether the observed improvement in behavioral prediction power of task-based FC can be attributed to changes in brain activity induced by the task design. We decomposed the task fMRI time course of each task into the task model fit (the fitted time course of the task condition regressors from the single-subject general linear model) and the task model residuals, calculated their respective FC, and compared the behavioral prediction performance of these FC estimates to resting-state FC and the original task-based FC. The FC of the task model fit was better than the FC of the task model residual and resting-state FC at predicting a measure of general cognitive ability or two measures of performance on the fMRI tasks. The superior behavioral prediction performance of the FC of the task model fit was content-specific insofar as it was only observed for fMRI tasks that probed similar cognitive constructs to the predicted behavior of interest. To our surprise, the task model parameters, the beta estimates of the task condition regressors, were equally if not more predictive of behavioral differences than all FC measures. These results showed that the observed improvement of behavioral prediction afforded by task-based FC was largely driven by the FC patterns associated with the task design. Together with previous studies, our findings highlighted the importance of task design in eliciting behaviorally meaningful brain activation and FC patterns.

Chu J, Ganson KT, Baker FC, Testa A, Jackson DB, Murray SB, Nagata JM. Screen time and suicidal behaviors among U.S. children 9-11 years old: A prospective cohort study. Prev Med. 2023 Feb 17;169:107452. doi: 10.1016/j.ypmed.2023.107452. Epub ahead of print. PMID: 36805495.

Suicide is a leading cause of death among adolescents. Emerging literature has described relationships between excessive screen time and suicidal behaviors, though findings have been mixed. The objective of this study is to determine the prospective associations between screen time and suicidal behaviors two-years later in a national (U.S.) cohort of 9-11-year-old-children. We analyzed prospective cohort data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11,633). Logistic regression analyses were estimated to determine the associations between baseline self-reported screen time (exposure) and suicidal behaviors (outcome) based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5) at two-year-follow-up. Participants reported an average of 4.0 h of total screen time per day at baseline. At two-year-follow-up, 1.38% of the sample reported at least one suicidal behavior. Each additional hour of total screen time was prospectively associated with 1.09 higher odds of suicidal behaviors at 2-year-follow-up (95% CI 1.03-1.14), after adjusting for covariates. For specific screen time modalities, each additional hour of texting (aOR 1.36, 95% CI 1.06-1.74), video chatting (aOR 1.30, 95% CI 1.03-1.65), watching videos (aOR 1.21, 95% CI 1.04-1.39), and playing video games (aOR 1.18, 95% CI 1.01-1.38) was associated with higher odds of subsequent suicidal behaviors. Higher screen time is associated with higher odds of reporting suicidal behaviors at two-year-follow-up. Future research should seek to identify how specific screen time experiences may influence suicidal behaviors.

Meca A, Peraza JA, Riedel MC, Hale W, Pettit JW, Musser ED, Salo T, Flannery JS, Bottenhorn KL, Dick AS, Pintos Lobo R, Ucros LM, Greaves CA, Hawes SW, Sanchez M, Gonzalez MR, Sutherland MT, Gonzalez R, Laird AR. Acculturative Orientations Among Hispanic/Latinx Caregivers in the ABCD Study: Associations With Caregiver and Youth Mental Health and Youth Brain Function. Biol Psychiatry Glob Open Sci. 2023 Feb 17;3(4):785-796. doi: 10.1016/j.bpsgos.2023.02.005. PMID: 37881576; PMCID: PMC10593892.

Background: Population-based neuroscience offers opportunities to examine important but understudied sociocultural factors such as acculturation. Acculturation refers to the extent to which an individual retains their cultural heritage and/or adopts the receiving society’s culture and is particularly salient among Hispanic/Latinx immigrants. Specific acculturative orientations have been linked to vulnerability to substance use, depression, and suicide and are known to influence family dynamics between caregivers and their children.

Methods: Using data from first- and second-generation Hispanic/Latinx caregivers in the Adolescent Brain Cognitive Development (ABCD) Study (N = 1057), we examined how caregivers’ acculturative orientation affects their mental health, as well as the mental health and brain function of their children. Neuroimaging analyses focused on regions associated with self- and affiliation-based social processing (ventromedial prefrontal cortex, insula, and temporoparietal junction).

Results: We identified 2 profiles of caregiver acculturation: bicultural (retains heritage culture while adopting U.S. culture) and detached (discards heritage culture and rejects U.S. culture). Bicultural caregivers exhibited fewer internalizing and externalizing problems than detached caregivers; furthermore, youth exhibited similar internalizing effects across caregiver profiles. In addition, youth with bicultural caregivers displayed increased resting-state brain activity (i.e., fractional amplitude of low-frequency fluctuations and regional homogeneity) in the left insula, which has been linked to psychopathology; however, differences in long-range functional connectivity were not significant.

Conclusions: Caregiver acculturation is an important familial factor that has been linked to significant differences in youth mental health and insula activity. Future work should examine sociocultural and neurodevelopmental changes across adolescence to assess health outcomes and determine whether localized, corticolimbic brain effects are ultimately translated into long-range connectivity differences.

Dash GF, Karalunas SL, Kenyon EA, Carter EK, Mooney MA, Nigg JT, Feldstein Ewing SW. Gene-by-Environment Interaction Effects of Social Adversity on Externalizing Behavior in ABCD Youth. Behav Genet. 2023 Feb 16. doi: 10.1007/s10519-023-10136-z. Epub ahead of print. PMID: 36795263.

This study tested whether multiple domains of social adversity, including neighborhood opportunity/deprivation and life stress, moderate genetic (A), common environmental (C), and unique environmental (E) influences on externalizing behaviors in 760 same-sex twin pairs (332 monozygotic; 428 dizygotic) ages 10-11 from the ABCD Study. Proportion of C influences on externalizing behavior increased at higher neighborhood adversity (lower overall opportunity). A decreased and C and E increased at lower levels of educational opportunity. A increased at lower health-environment and social-economic opportunity levels. For life stress, A decreased and E increased with number of experienced events. Results for educational opportunity and stressful life experiences suggest a bioecological gene-environment interaction pattern such that environmental influences predominate at higher levels of adversity, whereas limited access to healthcare, housing, and employment stability may potentiate genetic liability for externalizing behavior via a diathesis-stress mechanism. More detailed operationalization of social adversity in gene-environment interaction studies is needed.

Chen YY, Yim H, Lee TH. Negative impact of daily screen use on inhibitory control network in preadolescence: A two-year follow-up study. Dev Cogn Neurosci. 2023 Feb 16;60:101218. doi: 10.1016/j.dcn.2023.101218. Epub ahead of print. PMID: 36821878.

The COVID-19 pandemic has made an unprecedented shift in children’s daily lives. Children are increasingly spending time with screens to learn and connect with others. As the online environment rapidly substitutes in-person experience, understanding children’s neuropsychological trajectories associated with screen experiences is important. Previous findings suggest that excessive screen use can lead children to prefer more immediate rewards over delayed outcomes. We hypothesized that increased screen time delays a child’s development of inhibitory control system in the brain (i.e., fronto-striatal circuitry). By analyzing neuropsychological data from 8324 children (9-11ys) from the ABCD Study, we found that children who had more screen time showed a higher reward orientation and weaker fronto-striatal connectivity. Importantly, we found that the daily screen exposure mediated the effect of reward sensitivity on the development of the inhibitory control system in the brain over a two year period. These findings suggest possible negative long-term impacts of increased daily screen time on children’s neuropsychological development. The results further demonstrated that screen time influences dorsal striatum connectivity, which suggests that the effect of daily screen use is a habitual seeking behavior. The study provides neural and behavioral evidence for the negative impact of daily screen use on developing children.

Sharp TH, Elsabbagh M, Pickles A, Bedford R. The subcortical correlates of autistic traits in school-age children: a population-based neuroimaging study. Mol Autism. 2023 Feb 11;14(1):6. doi: 10.1186/s13229-023-00538-5. PMID: 36765403.

Background: There is emerging evidence that the neuroanatomy of autism forms a spectrum which extends into the general population. However, whilst several studies have identified cortical morphology correlates of autistic traits, it is not established whether morphological differences are present in the subcortical structures of the brain. Additionally, it is not clear to what extent previously reported structural associations may be confounded by co-occurring psychopathology. To address these questions, we utilised neuroimaging data from the Adolescent Brain Cognitive Development Study to assess whether a measure of autistic traits was associated with differences in child subcortical morphology, and if any observed differences persisted after adjustment for child internalising and externalising symptoms.

Methods: Our analyses included data from 7005 children aged 9-10 years (female: 47.19%) participating in the Adolescent Brain Cognitive Development Study. Autistic traits were assessed using scores from the Social Responsiveness Scale (SRS). Volumes of subcortical regions of interest were derived from structural magnetic resonance imaging data.

Results: Overall, we did not find strong evidence for an association of autistic traits with differences in subcortical morphology in this sample of school-aged children. Whilst lower absolute volumes of the nucleus accumbens and putamen were associated with higher scores of autistic traits, these differences did not persist once a global measure of brain size was accounted for.

Limitations: It is important to note that autistic traits were assessed using the SRS, of which higher scores are associated with general behavioural problems, and therefore may not be wholly indicative of autism-specific symptoms. In addition, individuals with a moderate or severe autism diagnosis were excluded from the ABCD study, and thus, the average level of autistic traits will be lower than in the general population which may bias findings towards the null.

Conclusions: These findings from our well-powered study suggest that other metrics of brain morphology, such as cortical morphology or shape-based phenotypes, may be stronger candidates to prioritise when attempting to identify robust neuromarkers of autistic traits.

Kunitoki K, Hughes D, Elyounssi S, Hopkinson CE, Bazer OM, Eryilmaz H, Dunn EC, Lee PH, Doyle AE, Roffman JL. Youth Team Sports Participation Associates With Reduced Dimensional Psychopathology Through Interaction With Biological Risk Factors. Biol Psychiatry Glob Open Sci. 2023 Feb 10;3(4):875-883. doi: 10.1016/j.bpsgos.2023.02.001. PMID: 37881582; PMCID: PMC10593891.

Background: Physical activity is associated with mental health benefits in youth. Here, we used causal inference and triangulation with 2 levels of biology to substantiate relationships between sports participation and dimensional psychopathology in youths.

Methods: Baseline data from the Adolescent Brain Cognitive Development (ABCD) Study, which recruited children from 9 to 10 years of age across the United States, were included in multilevel regression models to assess relationships between lifetime participation in team sports (TS), individual sports, and nonsports activities and Child Behavior Checklist (CBCL) scores. We calculated polygenic risk scores for 8 psychiatric disorders to assess interactions with sports exposure on CBCL scores among European descendants. Following rigorous quality control, FreeSurfer-extracted brain magnetic resonance imaging structural data were examined for mediation of CBCL-activities relationships.

Results: Among those with complete data (N = 10,411), causal estimates using inverse probability weighting associated lifetime TS exposure with a 1.05-point reduction in CBCL total (95% CI, -1.54 to -0.56, p < .0001) a relationship that was specific to TS and strengthened with more years of exposure. Associations of attention-deficit/hyperactivity disorder polygenic loading with CBCL total weakened in European children with TS exposure (n = 4041; beta = -0.93, SE = 0.38, p = .013). Furthermore, TS participation and lower CBCL each associated with increased subcortical volumes (n = 8197). Subcortical volume mediated 5.5% of TS effects on CBCL total.

Conclusions: Our findings support prior associations of TS participation with lower psychopathology in youths through additional studies that demonstrate specificity, dose response, and coherence across 2 levels of biology. Longitudinal studies that further clarify causal relationships may justify interventional studies of TS for high-risk youth.

Romer AL, Ren B, Pizzagalli DA (In Press, 2023). Brain Structure Relations With Psychopathology Trajectories in the Adolescent Brain Cognitive Development Study. Journal of the American Academy of Child & Adolescent Psychiatry, Available online 9 February 2023, https://doi.org/10.1016/j.jaac.2023.02.002

Objective: A general psychopathology (‘p’) factor captures shared variation across mental disorders. Structural neural alterations have been associated with p concurrently, but less is known about whether these alterations relate to within-person change in p over time, especially during preadolescence, a period of neurodevelopmental changes.

Method: We examined whether baseline brain structure was prospectively related to the trajectory of p and specific forms of psychopathology over two years in 9,220 preadolescents (aged 9-10 at baseline) from the Adolescent Brain Cognitive Development Study®. We conducted longitudinal multilevel models to determine whether baseline brain structure (volume, surface area, thickness) was associated with between-person differences and within-person change in p (from a higher-order confirmatory factor model) and internalizing, externalizing, neurodevelopmental, somatization, and detachment factor scores (from a correlated factors model) over three study waves.

Results: Smaller global volume and surface area, but not thickness, were associated with higher between-person levels of p, which persisted over time. None of the brain structure measures related to within-person change in p. Lower baseline cortical thickness was associated with steeper decreases in internalizing psychopathology, which was driven by lower thickness within sensorimotor and temporal regions.

Conclusion: These novel results identify specific brain structure features that might contribute to transdiagnostic psychopathology development in preadolescence. Children with smaller total brain volume and surface area may be vulnerable to persistent general psychopathology during preadolescence. Cortical thinning reflective of pruning and myelination in sensorimotor and temporal brain regions specifically may protect against increases in internalizing, but not general psychopathology during preadolescence.

Gustavson DE, Nayak S, Coleman PL, Iversen JR, Lense MD, Gordon RL, Maes HH. Heritability of Childhood Music Engagement and Associations with Language and Executive Function: Insights from the Adolescent Brain Cognitive Development (ABCD) Study. Behav Genet. 2023 Feb 9. doi: 10.1007/s10519-023-10135-0. Epub ahead of print. PMID: 36757558.

Music engagement is a powerful, influential experience that often begins early in life. Music engagement is moderately heritable in adults (~ 41-69%), but fewer studies have examined genetic influences on childhood music engagement, including their association with language and executive functions. Here we explored genetic and environmental influences on music listening and instrument playing (including singing) in the baseline assessment of the Adolescent Brain Cognitive Development study. Parents reported on their 9-10-year-old children’s music experiences (N = 11,876 children; N = 1543 from twin pairs). Both music measures were explained primarily by shared environmental influences. Instrument exposure (but not frequency of instrument engagement) was associated with language skills (r = .27) and executive functions (r = .15-0.17), and these associations with instrument engagement were stronger than those for music listening, visual art, or soccer engagement. These findings highlight the role of shared environmental influences between early music experiences, language, and executive function, during a formative time in development.

Wang Z, Zhou X, Gui Y, Liu M, Lu H. Multiple measurement analysis of resting-state fMRI for ADHD classification in adolescent brain from the ABCD study. Transl Psychiatry. 2023 Feb 6;13(1):45. doi: 10.1038/s41398-023-02309-5. PMID: 36746929.

Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in school-aged children. Its accurate diagnosis looks after patients’ interests well with effective treatment, which is important to them and their family. Resting-state functional magnetic resonance imaging (rsfMRI) has been widely used to characterize the abnormal brain function by computing the voxel-wise measures and Pearson’s correlation (PC)-based functional connectivity (FC) for ADHD diagnosis. However, exploring the powerful measures of rsfMRI to improve ADHD diagnosis remains a particular challenge. To this end, this paper proposes an automated ADHD classification framework by fusion of multiple measures of rsfMRI in adolescent brain. First, we extract the voxel-wise measures and ROI-wise time series from the brain regions of rsfMRI after preprocessing. Then, to extract the multiple functional connectivities, we compute the PC-derived FCs including the topographical information-based high-order FC (tHOFC) and dynamics-based high-order FC (dHOFC), the sparse representation (SR)-derived FCs including the group SR (GSR), the strength and similarity guided GSR (SSGSR), and sparse low-rank (SLR). Finally, these measures are combined with multiple kernel learning (MKL) model for ADHD classification. The proposed method is applied to the Adolescent Brain and Cognitive Development (ABCD) dataset. The results show that the FCs of dHOFC and SLR perform better than the others. Fusing multiple measures achieves the best classification performance (AUC = 0.740, accuracy = 0.6916), superior to those from the single measure and the previous studies. We have identified the most discriminative FCs and brain regions for ADHD diagnosis, which are consistent with those of published literature.

Dai HD, Pierce J, Beseler C, Abadi A, Zoucha K, Johnson R, Buckley J, Ramos AK. Hierarchical Modeling of Psychosocial, Parental, and Environmental Factors for Susceptibility to Tobacco Product Use in 9-10-Year-Old Children. J Adolesc Health. 2023 Feb;72(2):267-276. doi: 10.1016/j.jadohealth.2022.09.021. Epub 2022 Nov 21. PMID: 36424333.

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

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

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

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

Nagata JM, Smith N, Alsamman S, Lee CM, Dooley EE, Kiss O, Ganson KT, Wing D, Baker FC, Gabriel KP. Association of Physical Activity and Screen Time With Body Mass Index Among US Adolescents. JAMA Netw Open. 2023 Feb 1;6(2):e2255466. doi: 10.1001/jamanetworkopen.2022.55466. PMID: 36757695.

Importance: The Physical Activity Guidelines Advisory Committee Scientific Report identified important research gaps to inform future guidance for adolescents, including limited evidence on the importance of sedentary behaviors (screen time) and their interactions with physical activity for adolescent health outcomes, including overweight and obesity.

Objective: To identify the independent associations of physical activity and screen time categories, and the interactions between physical activity and screen time categories, with body mass index (BMI) and overweight and obesity in adolescents.

Design, setting, and participants: This cross-sectional study used data from the Adolescent Brain Cognitive Development (ABCD) Study collected from September 10, 2018, to September 29, 2020. Data were analyzed from July 8 to December 20, 2022. A total of 5797 adolescents aged 10 to 14 years from 21 racially and ethnically diverse study sites across the US were included in the analysis.

Exposures: Categories of total step count per day (with 1000 to 6000 steps per day indicating low, >6000 to 12 000 steps per day indicating medium, and >12 000 steps per day indicating high), as measured by a wearable digital device (Fitbit), and categories of self-reported screen time hours per day (with 0 to 4 hours per day indicating low, >4 to 8 hours per day indicating medium, and >8 hours per day indicating high).

Main outcomes and measures: Participant BMI was calculated as weight in kilograms divided by height in meters squared and converted into sex- and age-specific percentiles in accordance with the Centers for Disease Control and Prevention growth curves and definitions. Individuals were classified as having overweight or obesity if their BMI was in the 85th percentile or higher for sex and age.

Results: Among 5797 adolescents included in the analytic sample, 50.4% were male, 61.0% were White, 35.0% had overweight or obesity, and the mean (SD) age was 12.0 (0.6) years. Mean (SD) reported screen time use was 6.5 (5.4) hours per day, and mean (SD) overall step count was 9246.6 (3111.3) steps per day. In models including both screen time and step count, medium (risk ratio [RR], 1.24; 95% CI, 1.12-1.37) and high (RR, 1.29; 95% CI, 1.16-1.44) screen time categories were associated with higher overweight or obesity risk compared with the low screen time category. Medium (RR, 1.19; 95% CI, 1.06-1.35) and low (RR, 1.30; 95% CI, 1.11-1.51) step count categories were associated with higher overweight or obesity risk compared with the high step count category. Evidence of effect modification between screen time and step count was observed for BMI percentile. For instance, among adolescents with low screen use, medium step count was associated with a 1.55 higher BMI percentile, and low step count was associated with a 7.48 higher BMI percentile. However, among those with high screen use, step count categories did not significantly change the association with higher BMI percentile (low step count: 8.79 higher BMI percentile; medium step count: 8.76 higher BMI percentile; high step count: 8.26 higher BMI percentile).

Conclusions and relevance: In this cross-sectional study, a combination of low screen time and high step count was associated with lower BMI percentile in adolescents. These results suggest that high step count may not offset higher overweight or obesity risk for adolescents with high screen time, and low screen time may not offset higher overweight or obesity risk for adolescents with low step count. These findings addressed several research gaps identified by the Physical Activity Guidelines Advisory Committee Scientific Report and may be used to inform future screen time and physical activity guidance for adolescents.

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

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

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

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

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

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

Sakib MN, Best JR, Hall PA. Bidirectional Associations Between Adiposity and Cognitive Function and Mediation by Brain Morphology in the ABCD Study. JAMA Netw Open. 2023 Feb 1;6(2):e2255631. doi: 10.1001/jamanetworkopen.2022.55631. PMID: 36795417.

Importance: Most epidemiologic studies examine the brain as an outcome in relation to adiposity (ie, the brain-as-outcome perspective), but it is also a potential risk factor associated with adiposity accumulation over time (ie, the brain-as-risk factor perspective). The bidirectionality hypothesis has not been fully explored in adolescent samples previously.

Objective: To assess bidirectional associations between adiposity and cognitive function in youth and test mediational pathways through brain morphology (specifically the lateral prefrontal cortex [LPFC]), lifestyle behaviors, and blood pressure.

Design, setting, and participants: This cohort study uses data (wave 1-3; 2 years of follow-up) from the Adolescent Brain Cognitive Development (ABCD) Study, a long-term longitudinal investigation of brain development in the United States launched in 2015, which recruited 11 878 children aged 9 to 10 years at inception. Data analysis was performed from August 2021 to June 2022.

Main outcomes and measures: Multivariate multivariable regression analyses were used to assess bidirectional associations of indicators of cognitive function (eg, executive function, processing speed, episodic memory, receptive vocabulary and reading skills) and adiposity (eg, body mass index z scores [zBMI] and waist circumference [WC]). Mediators considered for this investigation were lifestyle variables (eg, diet and physical activity), blood pressure, and the morphology of the LPFC and its subregions.

Results: A total of 11 103 individuals (mean [SD] age, 9.91 [0.6] years; 5307 females [48%]; 8293 White individuals [75%] and 2264 Hispanic individuals [21%]) were included in the current study. Multivariate multivariable regression analyses revealed that higher baseline zBMI and WC were associated with worse follow-up episodic memory (β, -0.04; 95% CI, -0.07 to -0.01) and better vocabulary (β, 0.03; 95% CI, 0.002 to 0.06) task performance, in covariate adjusted models. Similarly, superior baseline executive function (zBMI: β, -0.03; 95% CI, -0.06 to -0.01; WC: β, -0.04; 95% CI, -0.07 to -0.01) and episodic memory (zBMI: β, -0.04; 95% CI, -0.07 to -0.02; WC: β, -0.03; 95% CI, -0.06 to -0.002) task performance were associated with better follow-up adiposity status in covariate adjusted models. Cross-lagged panel models with latent variable modeling had a bidirectional association with executive function task performance (brain-as-outcome: β, -0.02; 95% CI, -0.05 to -0.001; brain-as-risk factor: β, -0.01; 95% CI, -0.02 to -0.003). The hypothesized associations were statistically mediated by LPFC volume and thickness, physical activity, and blood pressure.

Conclusions and relevance: In this cohort study, executive function and episodic memory were bidirectionally associated with adiposity indices over time in this adolescent sample. These findings suggest that the brain can be both a risk factor and an outcome of adiposity; this complex bidirectional association should be taken into account in future research and clinical practice.

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

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

Sukumaran K, Cardenas-Iniguez C, Burnor E, Bottenhorn KL, Hackman DA, McConnell R, Berhane K, Schwartz J, Chen JC, Herting MM. Ambient fine particulate exposure and subcortical gray matter microarchitecture in 9- and 10-year-old children across the United States. iScience. 2023 Jan 31;26(3):106087. doi: 10.1016/j.isci.2023.106087. PMID: 36915692; PMCID: PMC10006642.

Neuroimaging studies showing the adverse effects of air pollution on neurodevelopment have largely focused on smaller samples from limited geographical locations and have implemented univariant approaches to assess exposure and brain macrostructure. Herein, we implement restriction spectrum imaging and a multivariate approach to examine how one year of annual exposure to daily fine particulate matter (PM2.5), daily nitrogen dioxide (NO2), and 8-h maximum ozone (O3) at ages 9-10 years relates to subcortical gray matter microarchitecture in a geographically diverse subsample of children from the Adolescent Brain Cognitive Development (ABCD) Study℠. Adjusting for confounders, we identified a latent variable representing 66% of the variance between one year of air pollution and subcortical gray matter microarchitecture. PM2.5 was related to greater isotropic intracellular diffusion in the thalamus, brainstem, and accumbens, which related to cognition and internalizing symptoms. These findings may be indicative of previously identified air pollution-related risk for neuroinflammation and early neurodegenerative pathologies.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Petrican R, Paine AL, Escott-Price V, Shelton KH. Overlapping brain correlates of superior cognition among children at genetic risk for Alzheimer’s disease and/or major depressive disorder. Sci Rep. 2023 Jan 18;13(1):984. doi: 10.1038/s41598-023-28057-6. PMID: 36653486; PMCID: PMC9849214.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Wade NE, Sullivan RM, Tapert SF, Pelham WE 3rd, Huestis MA, Lisdahl KM, Haist F. Concordance between substance use self-report and hair analysis in community-based adolescents. Am J Drug Alcohol Abuse. 2023 Jan 2;49(1):76-84. doi: 10.1080/00952990.2023.2164931. PMID: 36812240.

Background: Accurate drug use identification through subjective self-report and toxicological biosample (hair) analysis are necessary to determine substance use sequelae in youth. Yet consistency between self-reported substance use and robust, toxicological analysis in a large sample of youth is understudied. Objectives: We aim to assess concordance between self-reported substance use and hair toxicological analysis in community-based adolescents. Methods: Hair results by LC-MS/MS and GC-MS/MS and self-reported past-year substance use from an Adolescent Brain Cognitive Development (ABCD) Study subsample (N = 1,390; ages 9-13; 48% female) were compared. The participants were selected for hair selection through two methods: high scores on a substance risk algorithm selected 93%; 7% were low-risk, randomly selected participants. Kappa coefficients the examined concordance between self-report and hair results. Results: 10% of youth self-reported any past-year substance use (e.g. alcohol, cannabis, nicotine, and opiates), while a mostly non-overlapping 10% had hair results indicating recent substance use (cannabis, alcohol, non-prescription amphetamines, cocaine, nicotine, opiates, and fentanyl). In randomly selected low-risk cases, 7% were confirmed positive in hair. Combining methods, 19% of the sample self-reported substance use and/or had a positive hair sample. Kappa coefficient of concordance between self-report and hair results was low (kappa = 0.07; p = .007). Conclusions: Hair toxicology identified substance use in high-risk and low-risk ABCD cohort subsamples. Given low concordance between hair results and self-report, reliance on either method alone would incorrectly categorize 9% as non-users. Multiple methods for characterizing substance use history in youth improves accuracy. Larger representative samples are needed to assess the prevalence of substance use in youth.

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

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

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

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

Price JC, Lee JJ, Saraiya N, Lei S, Mintz CD. An Update on NIH Programs Relevant to Child Brain Health Research: ECHO, ABCD, HBCD, and MIRA. J Neurosurg Anesthesiol. 2023 Jan 1;35(1):119-123. doi: 10.1097/ANA.0000000000000875. Epub 2022 Dec 6. PMID: 36745173.