Scientific Publications

Abstract

Objective
The successful implementation and interpretation of machine learning (ML) models in epidemiological studies can be challenging without an extensive programming background. We provide a didactic example of machine learning for risk prediction in this study by determining whether early life factors could be useful for predicting adolescent psychopathology.

Methods
In total, 9643 adolescents ages 9–10 from the Adolescent Brain and Cognitive Development (ABCD) Study were included in ML analysis to predict high Child Behavior Checklist (CBCL) scores (i.e., t-scores ≥ 60). ML models were constructed using a series of predictor combinations (prenatal, family history, sociodemographic) across 5 different algorithms. We assessed ML performance through sensitivity, specificity, F1-score, and area under the curve (AUC) metrics.

Results
A total of 1267 adolescents (13.1 %) were found to have high CBCL scores. The best performing algorithms were elastic net and gradient boosted trees. The best performing elastic net models included prenatal and family history factors (Sensitivity 0.654, Specificity 0.713; AUC 0.742, F1-score 0.401) and prenatal, family, history, and sociodemographic factors (Sensitivity 0.668, Specificity 0.704; AUC 0.745, F1-score 0.402). Across all 5 ML algorithms, family history factors (e.g., either parent had nervous breakdowns, trouble holding jobs/fights/police encounters, and counseling for mental issues) and sociodemographic covariates (e.g., maternal age, child’s sex, caregiver income and caregiver education) tended to be better predictors of adolescent psychopathology. The most important prenatal predictors were unplanned pregnancy, birth complications, and pregnancy complications.

Conclusion
Our results suggest that inclusion of prenatal, family history, and sociodemographic factors in ML models can generate moderately accurate predictions of adolescent psychopathology. Issues associated with model overfitting, hyperparameter tuning, and system seed setting should be considered throughout model training, testing, and validation. Future early risk predictions models may improve with the inclusion of additional relevant covariates.

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Depression is a common consequence of traumatic brain injury. Separately, spontaneous depression-arising without brain injury-has been linked to abnormal responses in motivational neural circuitry to the anticipation or receipt of rewards. It is unknown if post-injury and spontaneously occurring depression share similar phenotypic profiles. This issue is compounded by the fact that nearly all examinations of these psychiatric sequelae are : there are rarely any prospective assessments of mood and neural functioning before and after a brain injury. In this Stage 2 Registered Report, we used the Adolescent Brain Cognitive Development Consortium dataset to examine if a disruption in functional neural responses to rewards is present in patients with depression after a mild traumatic brain injury. Notably, this study provides an unparalleled opportunity to examine the trajectory of neuropsychiatric symptoms longitudinally within-subjects. This allowed us to isolate mild traumatic brain injury-specific variance independent from pre-existing functioning. Here, we focus on a case-control comparison between 43 youth who experienced a mild traumatic brain injury between MRI visits, and 43 well-matched controls. Contrary to pre-registered predictions (https://osf.io/h5uba/), there was no statistically credible increase in depression in mild traumatic brain injury cases relative to controls. Mild traumatic brain injury was associated with subtle changes in motivational neural circuit recruitment during the anticipation of incentives on the Monetary Incentive Delay paradigm. Specifically, changes in neural recruitment appeared to reflect a failure to deactivate ‘task-negative’ brain regions (ventromedial prefrontal cortex), alongside blunted recruitment of ‘task-positive’ regions (anterior cingulate, anterior insula and caudate), during the anticipation of reward and loss in adolescents following mild brain injuries. Critically, these changes in brain activity were not correlated with depressive symptoms at either visit or depression change scores before and after the brain injury. Increased time since injury was associated with a recovery of cognitive functioning-driven primarily by processing speed differences-but depression did not scale with time since injury. These cognitive changes were also uncorrelated with neural changes after mild traumatic brain injury. This report provides evidence that acquired depression may not be observed as commonly after a mild traumatic brain injury in late childhood and early adolescence, relative to findings in adult cases. Several reasons for these differing findings are considered, including sampling enrichment in retrospective cohort studies, under-reporting of depressive symptoms in parent-report data, and neuroprotective factors in childhood and adolescence.

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The transition to adolescence is a critical period for mental health development. Socio-experiential environments play an important role in the emergence of depressive symptoms with some adolescents showing more sensitivity to social contexts than others. Drawing on recent developmental neuroscience advances, we examined whether hippocampal volume amplifies social context effects in the transition to adolescence. We analyzed 2-y longitudinal data from the Adolescent Brain Cognitive Development (ABCD) study in a diverse sample of 11,832 youth (mean age: 9.914 y; range: 8.917 to 11.083 y; 47.8% girls) from 21 sites across the United States. Socio-experiential environments (i.e., family conflict, primary caregiver’s depressive symptoms, parental warmth, peer victimization, and prosocial school environment), hippocampal volume, and a wide range of demographic characteristics were measured at baseline. Youth’s symptoms of major depressive disorder were assessed at both baseline and 2 y later. Multilevel mixed-effects linear regression analyses showed that negative social environments (i.e., family conflict, primary caregiver’s depressive symptoms, and peer victimization) and the absence of positive social environments (i.e., parental warmth and prosocial school environment) predicted greater increases in youth’s depressive symptoms over 2 y. Importantly, left hippocampal volume amplified social context effects such that youth with larger left hippocampal volume experienced greater increases in depressive symptoms in more negative and less positive social environments. Consistent with brain-environment interaction models of mental health, these findings underscore the importance of families, peers, and schools in the development of depression during the transition to adolescence and show how neural structure amplifies social context sensitivity.

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Background
Studies suggest that prosocial behavior, having high empathy and engaging in behaviors intended to benefit others, may predict mental health or vice versa; however, these findings have been mixed. The purpose of the current study was to examine the bidirectional relationships between prosocial behavior and dimensions of psychopathology in children.

Methods
The relationships between prosocial behavior and four dimensions of psychopathology (general psychopathology, internalizing symptoms, conduct problems, and attention-deficit/hyperactivity disorder symptoms) were examined longitudinally in children 9–12 years of age from the Adolescent Brain Cognitive Development Study (N = 9122). We used a random intercept cross-lagged panel model to distinguish between stable, trait-like (between-person) and time-dependent (within-person) fluctuations across a 24-month period.

Results
Between-person results revealed that prosocial behavior was negatively associated with general psychopathology and conduct problems while being positively associated with internalizing symptoms. Within-person results demonstrated that, out of four possible directional paths tested, one was significant. This path showed that greater general psychopathology and conduct problems at the first-year follow-up predicted fewer prosocial behaviors at the second-year follow-up, although the effect size was small. In contrast, prosocial behavior did not predict psychopathology dimensions for any year.

Conclusions
The results of this study suggest that prosocial behaviors have stable associations with psychopathology across preadolescence; however, evidence of a directional association in which psychopathology predicts fewer prosocial behaviors in the future was only modest.

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Background: Social determinants of health (SDOH) significantly influence health behaviors, including tobacco use among youth. Adversities such as perceived discrimination, perceived neighborhood stress, life trauma, and financial strain are stressors that may mediate the relationship between various SDOH and youth tobacco use. This study aims to investigate whether multidimensional adversities mediate the effects of SDOH on tobacco use among youth.

Methods: Data from the Adolescent Brain Cognitive Development (ABCD) study were used to test our hypotheses. The sample included a diverse cohort of youth aged 9-10 years old followed until they were 15-16 years old. We examined the effects of baseline parental education, household income, neighborhood income, and family structure on subsequent youth tobacco use. Structural equation models were used to test if adversities (perceived discrimination, life trauma, financial strain) operate as potential mediators.

Results: All ABCD participants were eligible for our analysis, regardless of race, ethnicity, or SDOHs (n = 11,878). The findings indicated that the effects of parental education, household income, neighborhood income, and family structure on youth tobacco use were partially mediated by adversities. Higher levels of parental education and household income were associated with lower tobacco use, and this relationship was weakened when accounting for adversities. Similarly, stable family structures and higher neighborhood income were linked to reduced tobacco use, with adversities playing a mediating role.

Conclusions: Multidimensional adversities partially mediate the relationship between SDOH at baseline and subsequent youth tobacco use. Interventions aimed at reducing youth tobacco use should address both the social determinants and multiple adversities experienced by adolescents. Policies to improve the educational and economic situations of families, enhance neighborhood environments, and support stable family structures all reduce youth tobacco use, with lower exposure to adversities explaining this effect.

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Mental illnesses are a leading cause of disability globally, and functional disability is often in part caused by cognitive impairments across psychiatric disorders. However, studies have consistently reported seemingly opposite findings regarding the association between cognition and psychiatric symptoms.

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Background: Minorities’ Diminished Returns (MDRs) theory posits that socioeconomic resources have weaker protective effects on health and behavior for racial and ethnic minorities compared to Whites. This study examines whether tobacco susceptibility, defined as curiosity, intention, and openness to future tobacco use, mediates the diminished returns of family income on tobacco initiation among Black adolescents.

Methods: Data from the Adolescent Brain Cognitive Development (ABCD) Study were analyzed. Participants were followed from age 9 to 16. All participants were tobacco naïve at baseline. Tobacco susceptibility was assessed through self-reported measures of curiosity, intention, and openness to future tobacco use. Structural equation modeling (SEM) was used to examine the relationship between family income, tobacco susceptibility, and tobacco initiation.

Results: Overall, 10,653 Black or White youth entered our analysis. The analysis revealed that higher family income was less effective in preventing tobacco initiation among Black adolescents. Tobacco susceptibility significantly predicted tobacco initiation and partially mediated the relationship between family income and tobacco initiation.

Conclusions: Tobacco susceptibility explains some of the diminished returns of family income on tobacco initiation among Black adolescents. Interventions aimed at reducing tobacco susceptibility may enhance the protective effects of family income and help mitigate health disparities.

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Background: Socioeconomic status (SES) is traditionally viewed as a protective factor against impulsivity and subsequent tobacco use in youth. The prevailing model suggests that higher SES is associated with lower impulsivity, which in turn reduces the likelihood of future tobacco use. However, this pathway may not hold uniformly across racial groups due to differences in impulsivity and the phenomenon of Minorities’ Diminished Returns (MDRs), where the protective effects of SES, such as educational attainment, tend to be weaker or even reversed for Black youth compared to their White counterparts.

Objectives: This study aims to examine the racial heterogeneity in the pathway from childhood SES to impulsivity and subsequent tobacco use initiation during adolescence, focusing on differences between Black and White youth.

Methods: Data were drawn from the Adolescent Brain Cognitive Development (ABCD) Study, which includes a diverse sample of youth aged 9 to 16 years. The analysis examined the relationship between baseline family SES (age 9), impulsivity (age 9), and subsequent tobacco use (ages 9 to 16). Impulsivity was measured using the Urgency, Premeditation (lack of), Perseverance (lack of), Sensation Seeking, and Positive Urgency Impulsive Behavior Scale (UPPS-P). Structural equation modeling (SEM) was employed, with analyses stratified by race to explore potential differences in these associations.

Results: Overall, 6,161 non-Latino White and 1,775 non-Latino Black adolescents entered our analysis. In the full sample, higher family SES was linked to lower childhood impulsivity and, consequently, less tobacco uses in adolescence. However, racial differences emerged upon stratification. Among White youth, higher SES was associated with lower impulsivity, leading to reduced tobacco use, consistent with the expected model. In contrast, among Black youth, higher SES was not associated with lower impulsivity, thereby disrupting the protective effect of SES on tobacco use through this pathway. These findings suggest that racial heterogeneity exists in the SES-impulsivity-tobacco use pathway, aligning with the MDRs framework, which highlights how structural factors may weaken the protective effects of high SES among Black youth.

Conclusions: These findings underscore the importance of considering racial heterogeneity in the relationships between SES, impulsivity, and tobacco use. The observed disparities suggest a need for targeted interventions that address the unique challenges faced by Black youth, who may not experience the same protective benefits of high SES as their White peers. These results carry significant implications for public health strategies aimed at reducing tobacco use in racially diverse populations.

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Objective
To determine whether anxiety and depression symptoms are mechanisms through which adverse childhood experiences (ACEs) contribute toward persistent/recurrent pain (PRP) across early adolescence.

Methods
This study described the direct and indirect (i.e. mediated) effects of ACEs on PRP across early adolescence, using four years of Adolescent Brain Cognitive Development Study® data. Annual pain frequency, anxiety, and depression symptoms were measured using the Child Behavior Checklist, and youth with pain for ≥3 of the 4-year study period were classified with PRP. Early (up to age 9-10 years; reported at baseline) and recent (at age 10-11 years; reported at year 1) ACE exposures were derived from parent and youth completed surveys. Structural equation modeling estimated the direct and indirect associations among early and recent ACEs, pain outcomes, and anxiety/depression symptoms reported in the year(s) in between.

Results
Among 7,951 youth, 2,540 (31.9%) were classified with PRP. Higher levels of early ACE exposure were associated with an increased probability of having PRP (adj.β 0.65 (95% Confidence Interval [CI] 0.07, 1.22). Early ACEs also had indirect effects on PRP via higher interim anxiety (adj. β 5.36 [95% CI 3.45, 7.26]) and depression symptoms (adj. β 4.57 [95% CI 3.01, 6.13]). Early and recent ACE exposures predicted higher pain frequency scores in subsequent years, with mixed results regarding the role of anxiety and depression in the relationships between ACEs and pain frequency scores.

Conclusion
Anxiety and depression symptoms are potentially important interventional targets to lower the risk for PRP among youth exposed to ACEs.

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Background: The initiation of substance use during adolescence is a significant public health concern with long-term implications. Structural and environmental factors, such as community-level crime statistics related to drug offenses, are often assumed to influence the likelihood of substance use among youth. However, the relationship between these environmental crime indicators and early substance use initiation in adolescents is not well understood.

Objective: This study aims to examine the association between environmental drug-related crime statistics—derived from Uniform Crime Reports, including drug abuse violations, drug sales, marijuana sales, drug possession, and driving under the influence (DUI)—and the use of tobacco, marijuana, and alcohol among adolescents aged 9-16 in the United States. Methods: Data from the Adolescent Brain Cognitive Development (ABCD) study, which follows a cohort of adolescents from ages 9-10 to 16, were analyzed. 11,878 participants entered our analysis. The primary environmental measures included total drug abuse violations, drug sale offenses, marijuana sale offenses, drug possession offenses, and DUI reports. Substance use outcomes of interest were the frequency and prevalence of tobacco, marijuana, and alcohol use across the observed age range.

Results: Contrary to expectations, higher levels of drug-related crime in a community were not associated with increased use of tobacco, marijuana, or alcohol among adolescents. In fact, the study found a significant inverse relationship between the total number of drug-related crimes and tobacco use, suggesting lower tobacco use in areas with higher reported drug abuse violations, drug sales, marijuana sales, drug possession, and DUI incidents. No significant associations were observed between these crime indicators and the use of marijuana or alcohol.

Conclusions: These findings challenge the prevailing assumption that higher environmental drug-related crime statistics necessarily predict greater substance use among adolescents. The observed inverse relationship between drug-related crime and tobacco use warrants further investigation to understand the underlying mechanisms and to inform targeted intervention strategies. Future research should explore the complex interplay between structural environmental factors and youth substance use to better inform public health policies.

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The neurobiological basis of working memory and delay discounting are theorized to overlap, but few studies have empirically examined these relations in large samples. To address this, we investigated the association of neural activation during an fMRI N-Back working memory task with delay discounting area, as well as in- and out-of-scanner working memory measures. These analyses were conducted in two large task fMRI datasets, the Human Connectome Project and the Adolescent Brain Cognitive Development Study. Although in- and out-of-scanner working memory performance were significantly associated with N-back task brain activation regions, contrary to our hypotheses, there were no significant associations between working memory task activation and delay discounting scores. These findings call into question the extent of the neural overlap in delay discounting and working memory and highlight the need for more investigations directly interrogating overlapping and distinct brain regions across cognitive neuroscience tasks.

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Persistent distressing psychotic-like experiences (PLE) are associated with impaired functioning and future psychopathology. Prior research suggests that physical activities may be protective against psychopathology. However, it is unclear whether physical activities may interact with genetics in the development of psychosis.

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Importance
Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.

Objective
To identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.

Design, Setting, and Participants
Multicenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.

Exposure
SARS-CoV-2 infection.

Main
Outcomes and Measures PASC and 89 prolonged symptoms across 9 symptom domains.

Results
A total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise–related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.

Conclusions and Relevance
This study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

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It is unclear how family factors affect health care utilization among youth with persistent or recurrent pain, despite potential relevance to interventions targeting treatment barriers.

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Background: Climate change has led to an increase in the frequency and intensity of extreme heat events, a trend expected to continue. This poses significant health risks, particularly for vulnerable populations like children. While previous research has largely concentrated on the physical health impacts of extreme heat, less attention has been given to behavioral outcomes, such as delinquency.

Objectives: This study investigates the association between extreme heat exposure and delinquency among children, utilizing data from the Adolescent Brain Cognitive Development (ABCD) study. It also explores the potential mediating roles of neighborhood socioeconomic status (SES; measured by median home value), puberty, peer deviance, and financial difficulties. Methods: Data from the national ABCD study were analyzed to assess the relationship between extreme heat exposure (exposure) and delinquency (outcome). Covariates included race/ethnicity, sex, and age. Mediators examined were neighborhood SES, puberty, peer deviance, and financial difficulties. Structural equation modeling (SEM) was employed for data analysis.

Results: Overall, 11,878 children entered our analysis. The analysis revealed a significant association between extreme heat exposure and higher levels of delinquency among children. Children more exposed to extreme heat were more likely to be Black, reside in lower SES neighborhoods, experience greater financial difficulties, and have more advanced puberty status. The group facing the highest heat exposure was also economically disadvantaged.

Conclusions: The findings suggest that children already disadvantaged by socio-economic factors are disproportionately affected by extreme heat, leading to increased delinquency. This highlights the need for targeted interventions to protect these vulnerable populations and address the mediators of extreme heat exposure. Future research should focus on longitudinal studies and evaluate the effectiveness of various mitigation strategies to address these disparities.

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Irritability, or an increased proneness to frustration and anger, is common in youth; however, few studies have examined neurostructural correlates of irritability in children. The purpose of the current study was to examine concurrent and longitudinal associations between brain structure and irritability in a large sample of 9-10-year-old children. Participants included 10,647 children from the Adolescent Brain Cognitive Development Study (ABCD Study). We related a latent irritability factor to gray matter volume, cortical thickness, and surface area in 68 cortical regions and to gray matter volume in 19 subcortical regions using structural equation modeling. Multiple comparisons were adjusted for using the false discovery rate (FDR). After controlling for age, sex, race/ethnicity, scanner model, parent’s highest level of education, medication use, and total intracranial volume, irritability was associated with smaller volumes in primarily temporal and parietal regions at baseline. Longitudinal analyses showed that baseline gray matter volume did not predict irritability symptoms at the 3rd-year follow-up. No significant associations were found for cortical thickness or surface area. The current study demonstrates inverse associations between irritability and volume in regions implicated in emotional processing/social cognition, attention allocation, and movement/perception. We advance prior research by demonstrating that neurostructural differences associated with irritability are already apparent by age 9-10 years, extending this work to children and supporting theories positing socioemotional deficits as a key feature of irritability.

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Background: Recent research has identified structural racism—systemic policies and practices that perpetuate racial inequalities—as a significant social determinant of population health. Studies utilizing data from the Adolescent Brain Cognitive Development (ABCD) study have shown an association between higher levels of state-level structural racism and increased tobacco use among youth in the United States. However, there has been limited exploration of the psychosocial mediators of this relationship, particularly in the context of youth aged 10-16 years.

Objective: This study aimed to assess the roles of socioeconomic status (SES), tobacco susceptibility, and perceived discrimination as potential mediators in the relationship between state-level structural racism and youth tobacco initiation rates.

Methods: We analyzed data from the ABCD study, a nationally representative longitudinal survey of 11,698 youth followed from ages 9/10 to 15/16. These data were combined with state-level indicators of structural racism. We employed structural equation modeling (SEM) to investigate the mediators of the association between structural racism and self-reported initiation of tobacco use, while controlling for individual and state-level covariates.

Results: Our findings indicate that higher levels of structural racism were associated with increased rates of tobacco initiation among youth. This relationship was partially mediated by lower SES, but not by perceived discrimination or tobacco susceptibility.

Conclusion: The association between structural racism and youth tobacco initiation appears to be influenced in part by the lower SES prevalent in states with higher levels of racism. These results highlight the need for addressing both racism and SES inequalities as key strategies for reducing tobacco disparities among youth.

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Elevated pediatric irritability is a transdiagnostic symptom that predicts multiple mental health problems in adolescence and adulthood. Altered top-down regulatory networks, such as inhibitory control networks that suppress an impulse in favor of goal-directed behavior, are thought to contribute to high levels of youth irritability. Nevertheless, little work has examined links between youth irritability and neural processes supporting inhibitory control in large diverse samples, nor have they focused on the key period ramping up to adolescence (i.e., preadolescence).

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Adolescents encounter a complex digital environment, yet existing data on youth technology use rarely differentiates technology subtypes. This study maps the evolution and intricacies of youth engagement with technology subtypes.

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Cannabis legalization has triggered an increase in prenatal cannabis use. Given that tobacco is commonly co-used with cannabis, determining outcomes associated with prenatal cannabis and tobacco co-exposure is crucial. While literature exists regarding the individual effects of prenatal cannabis and tobacco exposure on childhood behaviour, there is a gap regarding their combined use, which may have interactive effects. Therefore, we investigated whether prenatal cannabis and tobacco co-exposure was associated with greater externalizing and internalizing problems in middle childhood compared to prenatal exposure to either substance alone or no exposure.

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Few studies have explored the interplay of how individual identity, parental, familial, and contextual factors impact associations between Latinx adolescent adversities and psychopathology. This study aimed to examine if these factors mediate the relationship between adversities and psychopathology in Latinx youth.

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Prospective associations between preadolescent neurocognitive structure and onset of substance use in adolescence have not been examined. This study investigated associations between cognitive structure among youth aged 9 – 10 years and the likelihood of experimentation with tobacco and alcohol by ages 13-14 years.

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Preterm birth poses a major public health challenge, with significant and heterogeneous developmental impacts. Latent profile analysis was applied to the National Institutes of Health Toolbox performance of 1891 healthy prematurely born children from the Adolescent Brain and Cognitive Development study (970 boys, 921 girls; 10.00 ± 0.61 years; 1.3% Asian, 13.7% Black, 17.5% Hispanic, 57.0% White, 10.4% Other). Three distinct neurocognitive profiles emerged: consistently performing above the norm (19.7%), mixed scores (41.0%), and consistently performing below the norm (39.3%). These profiles were associated with lasting cognitive, neural, behavioral, and academic differences. These findings underscore the importance of recognizing diverse developmental trajectories in prematurely born children, advocating for personalized diagnosis and intervention to enhance care strategies and long-term outcomes for this heterogeneous population.

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To determine disparities in adverse childhood experiences (ACEs) by sexual identity in a national cohort of early adolescents.

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Background
Positive and negative alcohol expectancies (PAEs and NAEs, respectively) and impulsivity are key risk factors for the onset of alcohol use. While both factors independently contribute to alcohol initiation, the developmental aspects of AEs and their nuanced relationship with impulsivity are not adequately understood. Understanding these relationships is imperative for developing targeted interventions to prevent or delay alcohol use onset in youth.

Methods
This study utilized the Adolescent Brain Cognitive Development cohort to examine how PAEs and NAEs develop over time and relate to each other. We also explored how self-reported and behavioral impulsivity at baseline (~10 years old) are associated with the longitudinal development of PAEs and NAEs in youth Ages 11, 12, and 13 (n = 7,493; 7,500; and 6,981, respectively), as well as their time-specific relationships.

Results
Findings revealed while PAEs increased steadily over all three years, NAEs increased from ages 11 to 12 and then remained unchanged between 12 and 13. Overall, PAEs and NAEs were inversely related. Moreover, PAEs positively correlated with sensation seeking and lack of premeditation, while NAEs negatively correlated with positive urgency. Interestingly, a time-specific association was observed with PAEs and lack of perseverance, with a stronger correlation to PAEs at Age 11 compared to Age 12.

Conclusions
Overall, this study provides valuable insights into the divergent developmental trajectory of PAEs and NAEs, and their overall and time-specific associations with impulsivity. These findings may guide focused and time-sensitive prevention and intervention initiatives, aiming to modify AEs and reduce underage drinking.

Abbreviations
PAEs positive alcohol expectancies NAEsnegative alcohol expectancies ABCDAdolescent Brain Cognitive Development NU Negative Urgency PU Positive Urgency PRE Lack of Premeditation PERS Lack of Perseverance SS Sensation Seeking

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The prevalence of internalizing psychopathology rises precipitously from early to mid-adolescence, yet the underlying neural phenotypes that give rise to depression and anxiety during this developmental period remain unclear.

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This study used latent transition analysis to examine the stability and change in perceived threats in youth’s primary social contexts-neighborhoods, schools, and families-and associations with emotional and behavioral problems when youth transitioned from childhood to adolescence. The sample included 8208 racially and ethnically diverse youth enrolled in the Adolescent Brain Cognitive Development Study (47.4% female, M = 9.83, M = 11.99). Results revealed that while perceived threats in youth’s neighborhoods were considerably stable, perceived threats in youth’s families fluctuated in relation to stressful life events. Further, subgroups of youth characterized by elevated perceived threat experiences in different contexts showed differential associations with emotional and behavioral problems. Overall, findings highlight the importance of considering the stability of perceived threats to direct appropriate interventions.

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Chronotype refers to individual preference in circadian cycles and is associated with psychiatric problems. It is mainly classified into early (those who prefer to be active in the morning and sleep and wake up early) and late (those who prefer to be active in the evening and sleep and wake up late) chronotypes. Although previous research has demonstrated associations between chronotype and cognitive function and brain structure in adults, little is known regarding these associations in children. Here, we aimed to investigate the relationship between chronotype and cognitive function in children. Moreover, based on the significant association between chronotype and specific cognitive functions, we extracted regions-of-interest (ROI) and examined the association between chronotype and ROI volumes.

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Exposure to high levels of fine particulate matter (PM) with aerodynamic diameter () via air pollution may be a risk factor for psychiatric disorders during adulthood. Yet few studies have examined associations between exposure and the trajectory of symptoms across late childhood and early adolescence.

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Youth screen media activity is a growing concern, though few studies include objective usage data. Through the longitudinal, U.S.-based Adolescent Brain Cognitive Development (ABCD) Study, youth (m = 14; n = 1415) self-reported their typical smartphone use and passively recorded three weeks of smartphone use via the ABCD-specific Effortless Assessment Research System (EARS) application. Here we describe and validate passively-sensed smartphone keyboard and app use measures, provide code to harmonize measures across operating systems, and describe trends in adolescent smartphone use. Keyboard and app-use measures were reliable and positively correlated with one another (r = 0.33) and with self-reported use (rs = 0.21-0.35). Participants recorded a mean of 5 h of daily smartphone use, which is two more hours than they self-reported. Further, females logged more smartphone use than males. Smartphone use was recorded at all hours, peaking on average from 8 to 10 PM and lowest from 3 to 5 AM. Social media and texting apps comprised nearly half of all use. Data are openly available to approved investigators ( https://nda.nih.gov/abcd/ ). Information herein can inform use of the ABCD dataset to longitudinally study health and neurodevelopmental correlates of adolescent smartphone use.

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Conduct disorder is associated with the highest burden of any mental disorder in childhood, yet its neurobiology remains unclear. Inconsistent findings limit our understanding of the role of brain structure alterations in conduct disorder. This study aims to identify the most robust and replicable brain structural correlates of conduct disorder.

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Air pollution is ubiquitous, yet questions remain regarding its impact on the developing brain. Large changes occur in white matter microstructure across adolescence, with notable differences by sex.

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Introduction: Although psychotic behaviors can be difficult to assess in children, early identification of children at high risk for the emergence of psychotic symptoms may facilitate the prevention of related disorders. Psychotic-like experiences (PLEs), or subthreshold thought and perceptual disturbances, could be early manifestations of psychosis that may predict a future diagnosis of a psychosis-related disorder or nonspecific correlates of a wide range of psychological problems. Additional research is needed regarding how PLEs map onto dimensions of psychopathology in children.

Methods: In the present study, we examined the association between PLEs and general and specific dimensions of psychological problems in a sample of 10,692 children from the Adolescent Brain Cognitive Development Study (ABCD Study).

Results: The results of this study showed that self-reported PLEs were associated with a general psychopathology factor and an ADHD factor, which were defined in hierarchical models of parent-rated psychological problems.

Discussion: These findings suggest that PLEs are broadly associated with a wide range of psychological problems through the general psychopathology factor even before psychotic disorders typically manifest. This study supports the need for longitudinal analyses of future waves of the ABCD Study to determine if PLEs can detect children at high risk for serious psychological problems in adulthood.

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Children’s brains dynamically adapt to the stimuli from the internal state and the external environment, allowing for changes in cognitive and mental behavior. In this work, we performed a large-scale analysis of dynamic functional connectivity (DFC) in children aged 9~11 years, investigating how brain dynamics relate to cognitive performance and mental health at an early age. A hybrid independent component analysis framework was applied to the Adolescent Brain Cognitive Development (ABCD) data containing 10,988 children. We combined a sliding-window approach with k-means clustering to identify five brain states with distinct DFC patterns. Interestingly, the occurrence of a strongly connected state with the most within-network synchrony and the anticorrelations between networks, especially between the sensory networks and between the cerebellum and other networks, was negatively correlated with cognitive performance and positively correlated with dimensional psychopathology in children. Meanwhile, opposite relationships were observed for a DFC state showing integration of sensory networks and antagonism between default-mode and sensorimotor networks but weak segregation of the cerebellum. The mediation analysis further showed that attention problems mediated the effect of DFC states on cognitive performance. This investigation unveils the neurological underpinnings of DFC states, which suggests that tracking the transient dynamic connectivity may help to characterize cognitive and mental problems in children and guide people to provide early intervention to buffer adverse influences.

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Brain-phenotype predictive models seek to identify reproducible and generalizable brain-phenotype associations. External validation, or the evaluation of a model in external datasets, is the gold standard in evaluating the generalizability of models in neuroimaging. Unlike typical studies, external validation involves two sample sizes: the training and the external sample sizes. Thus, traditional power calculations may not be appropriate. Here we ran over 900 million resampling-based simulations in functional and structural connectivity data to investigate the relationship between training sample size, external sample size, phenotype effect size, theoretical power and simulated power. Our analysis included a wide range of datasets: the Healthy Brain Network, the Adolescent Brain Cognitive Development Study, the Human Connectome Project (Development and Young Adult), the Philadelphia Neurodevelopmental Cohort, the Queensland Twin Adolescent Brain Project, and the Chinese Human Connectome Project; and phenotypes: age, body mass index, matrix reasoning, working memory, attention problems, anxiety/depression symptoms and relational processing. High effect size predictions achieved adequate power with training and external sample sizes of a few hundred individuals, whereas low and medium effect size predictions required hundreds to thousands of training and external samples. In addition, most previous external validation studies used sample sizes prone to low power, and theoretical power curves should be adjusted for the training sample size. Furthermore, model performance in internal validation often informed subsequent external validation performance (Pearson’s r difference <0.2), particularly for well-harmonized datasets. These results could help decide how to power future external validation studies.

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Trauma exposure (TE) and cognitive flexibility (CF) are risk factors for self-injurious thoughts and behaviors (SITBs). However, it is unknown whether these risk factors contribute to mechanisms associated with distinct categories of SITBs. The current study examined the potential moderating role of TE in the relationships between CF and multiple SITBs, including active suicidal ideation (SI), passive SI, non-suicidal self-injury (NSSI), and history of suicide attempt (SA), among pre-adolescent children.

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Different types of early-life adversity have been associated with children’s brain structure and function. However, understanding the disparate influence of distinct adversity exposures on the developing brain remains a major challenge.

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Twin births are related with maternal and fetal adverse outcomes. Little was known about the comparability of the cognitive, behavioral development and brain structure between twins and singletons in early adolescence. This retrospective cohort study was based on data from the United States population-based, prospective, longitudinal observational Adolescent Brain Cognitive Development study. Children with complete twin status information were enrolled, and the exposure variable was twin status. Primary outcomes were cognitive, behavioral development and brain structure in early adolescence. Cognitive and behavioral outcomes were assessed by using the NIH Toolbox and Child Behavioral Checklist, respectively. Brain structure was evaluated by the cortical thickness, area, and volume extracted from the magnetic resonance imaging (MRI) data. Subgroup analyses were conducted by prematurity, birth weight, with sibling, genetic profiles, and twin types (zygosity). From 1st September 2016 to 15th November 2018, 11545 children (9477 singletons and 2068 twins) aged 9-10 years were enrolled. Twins showed mildly lower cognitive performance (|t|> 5.104, P-values < 0.001, False Discovery Rate [FDR] < 0.001), better behavioral outcome (|t|> 2.441, P-values < 0.015, FDR < 0.042), such as lower scores for multiple psychiatric disorders and behavioral issues, and smaller cortical volume (t = - 3.854, P-values < 0.001, FDR < 0.001) and cortical area (t = - 3.872, P-values < 0.001, FDR < 0.001). The observed differences still held when stratified for prematurity, birth weight, presence of siblings, genetic profiles, and twin types (zygosity). Furthermore, analyses on the two-year follow-up data showed consistent results with baseline data. Twin status is associated with lower cognitive and better behavioral development in early adolescence accompanied by altered brain structure. Clinicians should be aware of the possible difference when generalizing results from adolescent twin samples to singletons.

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Decades of research document an association between neurocognitive dysfunction and externalizing behaviors, including rule-breaking, aggression, and impulsivity. However, there has been very little work that examines how multiple neurocognitive functions co-occur within individuals and which combinations of neurocognitive functions are most relevant for externalizing behaviors. Moreover, Latent Profile Analysis (LPA), a widely used method for grouping individuals in person-centered analysis, often struggles to balance the tradeoff between good model fit (splitting participants into many latent profiles) and model interpretability (using only a few, highly distinct latent profiles). To address these problems, we implemented a non-parametric Bayesian form of LPA based on the Dirichlet process mixture model (DPM-LPA) and used it to study the relationship between neurocognitive functioning and externalizing behaviors in adolescents participating in the Adolescent Brain Cognitive Development Study. First, we found that DPM-LPA outperformed conventional LPA, revealing more distinct profiles and classifying participants with higher certainty. Second, latent profiles extracted from DPM-LPA were differentially related to externalizing behaviors: profiles with deficits in working memory, inhibition, and/or language abilities were robustly related to different expressions of externalizing. Together, these findings represent a step towards addressing the challenge of finding novel ways to use neurocognitive data to better describe the individual. By precisely identifying and specifying the variation in neurocognitive and behavioral patterns this work offers an innovative empirical foundation for the development of assessments and interventions that address these costly behaviors.

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Stress is associated with increased vulnerability to psychosis, yet the mechanisms that contribute to these effects are poorly understood. Substantial literature has linked reduced hippocampal volume to both psychosis risk and early life stress. However, less work has explored the direct and indirect effects of stress on psychosis through the hippocampus in preclinical samples- when vulnerability for psychosis is accumulating. The current paper leverages the Adolescent Brain Cognitive Development (ABCD) Study sample to examine whether objective psychosocial stressors, specifically adverse childhood experiences (ACE), are linked to vulnerability for psychosis, measured by psychotic-like experiences (PLE) severity, in late childhood and early adolescence, both directly and indirectly through the deleterious effects of stress on the hippocampus. Baseline data from 11,728 individuals included previously examined and validated items to assess ACE exposure, hippocampal volume, and PLE severity – a developmentally appropriate metric of risk for psychosis. Objective psychosocial stress exposure in childhood was associated with elevated PLE severity during the transition from childhood to adolescence. Hippocampal volume was significantly reduced in individuals with greater PLE severity and greater childhood stress exposure compared to peers with low symptoms or low stress exposure. These findings are consistent with a hippocampal vulnerability model of psychosis risk. Stress exposure may cumulatively impact hippocampal volume and may also reflect a direct pathway of psychosis risk. Objective psychosocial stress should be considered as a treatment target that may impact neurodevelopment and psychosis risk.

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Attention-deficit/hyperactivity disorder (ADHD) is among the most prevalent, inheritable, and heterogeneous childhood-onset neurodevelopmental disorders. Children with a hereditary background of ADHD have heightened risk of having ADHD and persistent impairment symptoms into adulthood. These facts suggest distinct familial-specific neuropathological substrates in ADHD that may exist in anatomical components subserving attention and cognitive control processing pathways during development. The objective of this study is to investigate the topological properties of the gray matter (GM) structural brain networks in children with familial ADHD (ADHD-F), non-familial ADHD (ADHD-NF), as well as matched controls. A total of 452 participants were involved, including 132, 165 and 155 in groups of ADHD-F, ADHD-NF and typically developed children, respectively. The GM structural brain network was constructed for each group using graph theoretical techniques with cortical and subcortical structures as nodes and correlations between volume of each pair of the nodes within each group as edges, while controlled for confounding factors using regression analysis. Relative to controls, children in both ADHD-F and ADHD-NF groups showed significantly higher nodal global and nodal local efficiencies in the left caudal middle frontal gyrus. Compared to controls and ADHD-NF, children with ADHD-F showed distinct structural network topological patterns associated with right precuneus (significantly higher nodal global efficiency and significantly higher nodal strength), left paracentral gyrus (significantly higher nodal strength and trend toward significantly higher nodal local efficiency) and left putamen (significantly higher nodal global efficiency and trend toward significantly higher nodal local efficiency). Our results for the first time in the field provide evidence of familial-specific structural brain network alterations in ADHD, that may contribute to distinct clinical/behavioral symptomology and developmental trajectories in children with ADHD-F.

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Parental incarceration is an adverse childhood experience that inequitably burdens families of color and affects millions of U.S. children and adolescents. Although racialized disparities in exposure to parental incarceration are often acknowledged, researchers have yet to examine whether manifestations of racism may affect the link between parental incarceration and youth outcomes. This study provides a first look at how parental incarceration relates to health vulnerabilities in the Adolescent Brain Cognitive Development (ABCD) study, an ongoing, population-based study of U.S. children born between 2006 and 2008. We start by describing exposure to parental incarceration and then examine how parental incarceration, state-level racial prejudice, and discrimination relate to health risks among 9191 White (66%), Black (19%), or Hispanic (15%) youth. Consistent with what we know about pervasive racialized disparities in the U.S. criminal legal system, we find that 19.3% of Black children in our sample have experienced parental incarceration, followed by 7.8% of Hispanic children, and 4.8% of White children. Results of multilevel mixed models further indicate that parental incarceration was associated with increased health risks among White children whereas family economic hardship and discrimination experiences were more robustly associated with health vulnerabilities among Black and Hispanic children. Additional analyses explored whether parental incarceration was associated with other outcomes among Black and Hispanic children, revealing increased risk for behavior problems contingent upon parental incarceration and discrimination for Black children and Hispanic boys. Among Hispanic girls, parental incarceration was associated with increased risk of behavior problems in states with higher levels of racism. Results suggest that parental incarceration contributes to risk among early adolescents across racialized groups, but that the specific toll it takes depends on outcomes assessed and the context in which it occurs.

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Girls and boys presenting disruptive behavior disorders (DBDs) display differences in white matter microstructure (WMM) relative to typically developing (TD) sex-matched peers. Boys with DBDs are at increased risk for traumatic brain injuries (TBIs), which are also known to impact WMM. This study aimed to disentangle associations of WMM with DBDs and TBIs.

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The current study investigated the prospective relationships between parental monitoring, family conflict, and screen time across six screen time modalities in early adolescents in the USA.

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Having multiple previous generations with depression in the family increases offspring risk for psychopathology. Parental depression has been associated with smaller subcortical brain volumes in their children, but whether two prior generations with depression is associated with further decreases is unclear.

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A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.

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Suicide is the third-leading cause of death among US adolescents. Environmental and lifestyle factors influence suicidal behavior and can inform risk classification, yet quantifying and incorporating them in risk assessment presents a significant challenge for reproducibility and clinical translation.

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Adolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to limited large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages, and the neurobiological basis underlying individual heterogeneity remains poorly understood. Here we identify, using the IMAGEN adolescent cohort followed up over 9 years (14-23 y), three groups of adolescents characterized by distinct developmental patterns of whole-brain gray matter volume (GMV). Group 1 show continuously decreasing GMV associated with higher neurocognitive performances than the other two groups during adolescence. Group 2 exhibit a slower rate of GMV decrease and lower neurocognitive performances compared with Group 1, which was associated with epigenetic differences and greater environmental burden. Group 3 show increasing GMV and lower baseline neurocognitive performances due to a genetic variation. Using the UK Biobank, we show these differences may be attenuated in mid-to-late adulthood. Our study reveals clusters of adolescent neurodevelopment based on GMV and the potential long-term impact.

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Lack of sleep has been found to be associated with cognitive impairment in children, yet the neural mechanism underlying this relationship remains poorly understood. To address this issue, this study utilized the data from the Adolescent Brain Cognitive Development (ABCD) study ( = 4930, aged 9-10), involving their sleep assessments, cognitive measures, and functional magnetic resonance imaging (fMRI) during an emotional n-back task. Using partial correlations analysis, we found that the out-of-scanner cognitive performance was positively correlated with sleep duration. Additionally, the activation of regions of interest (ROIs) in frontal and parietal cortices for the 2-back versus 0-back contrast was positively correlated with both sleep duration and cognitive performance. Mediation analysis revealed that this activation significantly mediated the relationship between sleep duration and cognitive function at both individual ROI level and network level. After performing analyses separately for different sexes, it was revealed that the mediation effect of the task-related activation was present in girls ( = 2546). These findings suggest that short sleep duration may lead to deficit in cognitive function of children, particularly in girls, through the modulation of frontoparietal activation during working memory load.

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Both cannabis use and depressive symptomology increase in prevalence throughout adolescence. Concurrently, the brain is undergoing neurodevelopment in important limbic regions, such as the amygdala. Prior research indicates the amygdala may also be related to cannabis use and depressive symptoms. We aimed to investigate the effects of adolescent cannabis use on amygdala volumes as well as the interaction of cannabis use and amygdala morphometry on depressive symptoms in youth.

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To progress adolescent mental health research beyond our present achievements – a complex account of brain and environmental risk factors without understanding neurobiological embedding in the environment – we need methods to unveil relationships between the developing brain and real-world environmental experiences.

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This study aimed to investigate the relationships between four types of perceived discrimination (based on race/ethnicity, nationality/country of origin, gender identity, weight/body size), individually and cumulatively; positive childhood experiences (PCEs); and behavioral symptoms among pre-adolescent youth.

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The human subcortex plays a pivotal role in cognition and is widely implicated in the pathophysiology of many psychiatric disorders. However, the heritability of functional gradients based on subcortico-cortical functional connectivity remains elusive. Here, leveraging twin functional MRI (fMRI) data from both the Human Connectome Project (n = 1023) and the Adolescent Brain Cognitive Development study (n = 936) datasets, we construct large-scale subcortical functional gradients and delineate an increased principal functional gradient pattern from unimodal sensory/motor networks to transmodal association networks. We observed that this principal functional gradient is heritable, and the strength of heritability exhibits a heterogeneous pattern along a hierarchical unimodal-transmodal axis in subcortex for both young adults and children. Furthermore, employing a machine learning framework, we show that this heterogeneous pattern of the principal functional gradient in subcortex can accurately discern the relationship between monozygotic twin pairs and dizygotic twin pairs with an accuracy of 76.2% (P < 0.001). The heritability of functional gradients is associated with the anatomical myelin proxied by MRI-derived T1-weighted/T2-weighted (T1w/T2w) ratio mapping in subcortex. This study provides new insights into the biological basis of subcortical functional hierarchy by revealing the structural and genetic properties of the subcortical functional gradients.

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Sex and gender are associated with human behavior throughout the life span and across health and disease, but whether they are associated with similar or distinct neural phenotypes is unknown. Here, we demonstrate that, in children, sex and gender are uniquely reflected in the intrinsic functional connectivity of the brain. Somatomotor, visual, control, and limbic networks are preferentially associated with sex, while network correlates of gender are more distributed throughout the cortex. These results suggest that sex and gender are irreducible to one another not only in society but also in biology.

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Sex and gender differences exist in the prevalence and clinical manifestation of common brain disorders. Identifying their neural correlates may help improve clinical care.

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Research has documented that adolescent sleep is impacted by various stressors, including interpersonal experiences and structural disadvantage. This study extends existing knowledge by empirically examining interconnected individual experiences of structural inequity and assessing its association with subjective and objective sleep outcomes.

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To determine prospective associations between bedtime screen use behaviors and sleep outcomes one year later in a national study of early adolescents in the United States.

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Childhood obesity and its adverse health consequences have risen worldwide, with low socioeconomic status increasing the risk in high-income countries like the US. Understanding the interplay between childhood obesity, cognition, socioeconomic factors, and the brain is crucial for prevention and treatment. Using data from the ABCD study, we investigated how body mass index (BMI) relates to brain structural and functional connectivity metrics. Obese/overweight children (n = 2,356) were more likely to live in poverty and exhibited lower cognitive performance compared to normal weight children (n = 4,754). Higher BMI was associated with multiple brain measures that were strongest for lower longitudinal diffusivity in corpus callosum, increased activity in cerebellum, insula, and somatomotor cortex, and decreased functional connectivity in multimodal brain areas, with effects more pronounced among children from low-income families. Notably, nearly 80% of the association of low income and 70% of the association of impaired cognition on BMI were mediated by higher brain activity in somatomotor areas. Increased resting activity in somatomotor areas and decreased structural and functional connectivity likely contribute to the higher risk of overweight/obesity among children from low-income families. Supporting low-income families and implementing educational interventions to improve cognition may promote healthy brain function and reduce the risk of obesity.

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Sleep is essential to adolescent development. Sexual and gender minority (SGM; e.g., lesbian, gay, bisexual, transgender) adults are at high risk for poor sleep, partially due to minority stress (e.g., discrimination). However, sleep has rarely been studied among SGM adolescents. In a national sample of early adolescents, we analyzed sexual minority (SM) and gender minority (GM) identity, gender incongruence, and gender nonconformity in association with sleep and tested minority and general stressors as mediators.

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There is a dearth of statistical models that adequately capture the total signal attributed to whole-brain imaging features. The total signal is often widely distributed across the brain, with individual imaging features exhibiting small effect sizes for predicting neurobehavioral phenotypes. The challenge of capturing the total signal is compounded by the distribution of neurobehavioral data, particularly responses to psychological questionnaires, which often feature zero-inflated, highly skewed outcomes. To close this gap, 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 estimates the fraction of variance explained (FVE) and the proportion of non-null effects (PNN) from large-scale imaging data. In simulations, ZIV demonstrates superior performance over other linear models. When applied to data from the Adolescent Brain Cognitive Development (ABCD) Study, we found that whole-brain imaging features contribute to a larger FVE for externalizing behaviors compared to internalizing behaviors. Moreover, focusing on features contributing to the PNN, ZIV estimator localized key neurocircuitry associated with neurobehavioral traits. To the best of our knowledge, the ZIV estimator is the first specialized method for analyzing zero-inflated neuroimaging data, enhancing future studies on brain-behavior relationships and improving the understanding of neurobehavioral disorders.

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Objective
This paper investigated the effects of prenatal drug exposure (PDE), childhood trauma (CT), and their interactions on the neurobiological markers for emotion processing.

Method
Here, in a non-clinical sample of pre-adolescents (nine to ten years old) from the Adolescent Brain Cognitive Development (ABCD) study (N=6,146), we investigate the impact of PDE to commonly used substances (i.e., alcohol, cigarettes, and marijuana), CT, and their interaction on emotion processing. From the Emotional N-back fMRI task data, we selected 26 regions of interests, previously implicated in emotion processing, and conducted separate linear mixed models (108 total) and accounted for available environmental risk factors.

Results
PDE was associated with reductions in response bias related to the processing of fearful compared to happy faces in widespread cortical regions (including the superior frontal and fusiform gyri and the inferior parietal lobule). Reduced response bias in the superior frontal gyrus emerged as a PDE-driven and was present regardless of CT status, but correlated with several items on the Child Behavior Checklist only in those children with both PDE and CT. The lower response bias of the left inferior parietal lobule, on the other hand, was observed only in children with both PDE and CT and correlated with internalizing and externalizing behaviors.

Conclusion
The study’s results support the diathesis-stress model and suggest that PDE may confer vulnerability to the effects of later CT through altered neurodevelopment. Children experiencing these “double hit” conditions may represent at-risk individuals who could benefit from early interventions to mitigate the onset of psychopathology. Because of limitations in the way PDE was reported in the ABCD study, including lack of severity measures and retrospective reporting, results are not sufficient for making recommendations or dictating policy for pregnant persons. Nevertheless, this study is a necessary first step in examining the interactive effects of prenatal and early-life exposures and many aspects of the sociodemographic and psychological environment.

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Efficiency of evidence accumulation (EEA), an individual’s ability to selectively gather goal-relevant information to make adaptive choices, is thought to be a key neurocomputational mechanism associated with cognitive functioning and transdiagnostic risk for psychopathology. However, the neural basis of individual differences in EEA is poorly understood, especially regarding the role of largescale brain network dynamics. We leverage data from 5198 participants from the Human Connectome Project and Adolescent Brain Cognitive Development Study to demonstrate a strong association between EEA and flexible adaptation to cognitive demand in the “task-positive” frontoparietal and dorsal attention networks. Notably, individuals with higher EEA displayed divergent task-positive network activation across n-back task conditions: higher activation under high cognitive demand (2-back) and lower activation under low demand (0-back). These findings suggest that brain networks’ flexible adaptation to cognitive demands is a key neural underpinning of EEA.

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The need to select mediators from a high dimensional data source, such as neuroimaging data and genetic data, arises in much scientific research. In this work, we formulate a multiple-hypothesis testing framework for mediator selection from a high-dimensional candidate set, and propose a method, which extends the recent development in false discovery rate (FDR)-controlled variable selection with knockoff to select mediators with FDR control. We show that the proposed method and algorithm achieved finite sample FDR control. We present extensive simulation results to demonstrate the power and finite sample performance compared with the existing method. Lastly, we demonstrate the method for analyzing the Adolescent Brain Cognitive Development (ABCD) study, in which the proposed method selects several resting-state functional magnetic resonance imaging connectivity markers as mediators for the relationship between adverse childhood events and the crystallized composite score in the NIH toolbox.

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Adolescence is a period in which mental health problems emerge. Research suggests that the COVID-19 lockdown may have worsened emotional and behavioral health.

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Canonical correlation analysis (CCA) and partial least squares correlation (PLS) detect linear associations between two data matrices by computing latent variables (LVs) having maximal correlation (CCA) or covariance (PLS). This study compared the similarity and generalizability of CCA- and PLS-derived brain-behavior relationships. Data were accessed from the baseline Adolescent Brain Cognitive Development (ABCD) dataset ( > 9,000, 9-11 years). The brain matrix consisted of cortical thickness estimates from the Desikan-Killiany atlas. Two phenotypic scales were examined separately as the behavioral matrix; the Child Behavioral Checklist (CBCL) subscale scores and NIH Toolbox performance scores. Resampling methods were used to assess significance and generalizability of LVs. LV for the CBCL brain relationships was found to be significant, yet not consistently stable or reproducible, across CCA and PLS models (singular value: CCA = .13, PLS = .39, < .001). LV for the NIH brain relationships showed similar relationships between CCA and PLS and was found to be stable and reproducible (singular value: CCA = .21, PLS = .43, < .001). The current study suggests that stability and reproducibility of brain-behavior relationships identified by CCA and PLS are influenced by the statistical characteristics of the phenotypic measure used when applied to a large population-based pediatric sample.

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Prenatal substance exposure (PSE) can lead to various harmful outcomes for the developing fetus and is linked to many emotional, behavioral, and cognitive difficulties later in life. Therefore, examination of the relationship between the development of associated brain structures and PSE is important for the development of more specific or new preventative methods.

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Neuroimaging-based prediction of neurocognitive measures is valuable for studying how the brain’s structure relates to cognitive function. However, the accuracy of prediction using popular linear regression models is relatively low. We propose a novel deep regression method, namely , that allows full supervision for contrastive learning in regression tasks using diffusion MRI tractography. TractoSCR performs supervised contrastive learning by using the absolute difference between continuous regression labels (i.e., neurocognitive scores) to determine positive and negative pairs. We apply TractoSCR to analyze a large-scale dataset including multi-site harmonized diffusion MRI and neurocognitive data from 8,735 participants in the Adolescent Brain Cognitive Development (ABCD) Study. We extract white matter microstructural measures using a fine parcellation of white matter tractography into fiber clusters. Using these measures, we predict three scores related to domains of higher-order cognition (general cognitive ability, executive function, and learning/memory). To identify important fiber clusters for prediction of these neurocognitive scores, we propose a permutation feature importance method for high-dimensional data. We find that TractoSCR obtains significantly higher accuracy of neurocognitive score prediction compared to other state-of-the-art methods. We find that the most predictive fiber clusters are predominantly located within the superficial white matter and projection tracts, particularly the superficial frontal white matter and striato-frontal connections. Overall, our results demonstrate the utility of contrastive representation learning methods for regression, and in particular for improving neuroimaging-based prediction of higher-order cognitive abilities. Our code will be available at: https://github.com/SlicerDMRI/TractoSCR.

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Neuroimaging has been widely adopted in psychiatric research, with hopes that these non-invasive methods will provide important clues to the underpinnings and prediction of various mental health symptoms and outcomes. However, the translational impact of neuroimaging has not yet reached its promise, despite the plethora of computational methods, tools, and datasets at our disposal. Some have lamented that too many psychiatric neuroimaging studies have been underpowered with respect to sample size. In this review, we encourage this discourse to shift from a focus on sheer increases in sample size to more thoughtful choices surrounding experimental study designs. We propose considerations at multiple decision points throughout the study design, data modeling and analysis process that may help researchers working in psychiatric neuroimaging boost power for their research questions of interest without necessarily increasing sample size. We also provide suggestions for leveraging multiple datasets to inform each other and strengthen our confidence in the generalization of findings to both population-level and clinical samples. Through a greater emphasis on improving the quality of brain-based and clinical measures rather than merely quantity, meaningful and potentially translational clinical associations with neuroimaging measures can be achieved with more modest sample sizes in psychiatry.

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The inequitable distribution of economic resources and exposure to adversity between racial groups contributes to mental health disparities within the United States. Consideration of the potential neurodevelopmental consequences, however, has been limited particularly for neurocircuitry known to regulate the emotional response to threat. Characterizing the consequences of inequity on threat neurocircuitry is critical for robust and generalizable neurobiological models of psychiatric illness. Here we use data from the Adolescent Brain and Cognitive Development Study 4.0 release to investigate the contributions of individual and neighborhood-level economic resources and exposure to discrimination. We investigate the potential appearance of race-related differences using both standard methods and through population-level normative modeling. We show that, in a sample of white and Black adolescents, racial inequities in socioeconomic factors largely contribute to the appearance of race-related differences in cortical thickness of threat neurocircuitry. The race-related differences are preserved through the use of population-level models and such models also preserve associations between cortical thickness and specific socioeconomic factors. The present findings highlight that such socioeconomic inequities largely underlie race-related differences in brain morphology. The present findings provide important new insight for the generation of generalizable neurobiological models of psychiatric illness.

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Alcohol, the most consumed drug in the United States, is associated with various psychological disorders and abnormal personality traits. Despite extensive research on adolescent alcohol consumption, the impact of early alcohol sipping patterns on changes in personality and mental health over time remains unclear. There is also limited information on the latent trajectory of early alcohol sipping, beginning as young as 9-10 years old. The dorsal anterior cingulate cortex (dACC) is crucial for cognitive control and response inhibition. However, the role of the dACC remains unclear in the relationship between early alcohol sipping and mental health outcomes and personality traits over time.

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Obese adults are often reported to have smaller brain volumes than their non-obese peers. Whether this represents evidence of accelerations in obesity-driven atrophy or is instead a legacy of developmental differences established earlier in the lifespan remains unclear. This study aimed to investigate whether early-life differences in adiposity explain differences in numerous adult brain traits commonly attributed to mid-life obesity. We utilised a two-sample lifecourse Mendelian randomization study in 37,501 adults recruited to UK Biobank (UKB) imaging centers from 2014, with secondary analyses in 6,996 children assessed in the Adolescent Brain Cognitive Development Study (ABCD) recruited from 2018. Exposures were genetic variants for childhood (266 variants) and adult (470 variants) adiposity derived from a GWAS of 407,741 UKB participants. Primary outcomes were adult total brain volume; grey matter volume, thickness, and surface area; white matter volume and hyperintensities; and hippocampus, amygdala, and thalamus volumes at mean age 55 in UKB. Secondary outcomes were equivalent childhood measures collected at mean age 10 in ABCD. In UKB, individuals who were genetically-predicted to have had higher levels of adiposity in childhood were found to have multiple smaller adult brain volumes relative to intracranial volume (e.g. z-score difference in normalised brain volume per category increase in adiposity [95%CI] = -0.20 [-0.28, -0.12]; p = 4 × 10-6). These effect sizes remained essentially unchanged after accounting for birthweight or current adult obesity in multivariable models, whereas most observed adult effects attenuated towards null (e.g. adult z-score [95%CI] for total volume = 0.06 [-0.05,0.17]; p = 0.3). Observational analyses in ABCD showed a similar pattern of changes already present in those with a high BMI by age 10 (z-score [95%CI] = -0.10 [-0.13, -0.07]; p = 8 × 10-13), with follow-up genetic risk score analyses providing some evidence for a causal effect already at this early age. Sensitivity analyses revealed that many of these effects were likely due to the persistence of larger head sizes established in those who gained excess weight in childhood (childhood z-score [95%CI] for intracranial volume = 0.14 [0.05,0.23]; p = 0.002), rather than smaller brain sizes per se. Our data suggest that persistence of early-life developmental differences across the lifecourse may underlie numerous neuroimaging traits commonly attributed to obesity-related atrophy in later life.

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Transparency can build trust in the scientific process, but scientific findings can be undermined by poor and obscure data use and reporting practices. The purpose of this work is to report how data from the Adolescent Brain Cognitive Development (ABCD) Study has been used to date, and to provide practical recommendations on how to improve the transparency and reproducibility of findings.

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Evidence suggests that adolescents engage in less physical activity during the summer break. Less is known regarding physical activity during the summer months of the COVID-19 pandemic.

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To investigate relationships of breastfeeding duration with brain structure and adiposity markers in youth and how these relationships are modified by neighborhood socioeconomic environments (SEEs).

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Psychotic-like experiences (PLEs) during adolescence can lead to psychotic disorders. Digital media usage has been suggested to link to PLEs, but research is limited on how different types of screen exposure may differentially relate to PLEs over time. This study aimed to examine longitudinal associations between screen usage patterns and PLEs in adolescents.

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Cross-sectional studies in adults have demonstrated associations between early life adversity (ELA) and reduced hippocampal volume, but the timing of these effects is not clear. The present study sought to examine whether ELA predicts changes in hippocampal volume over time in a large sample of early adolescents.

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The brain undergoes extensive development during late childhood and early adolescence. Cortical thinning is a prominent feature of this development, and some researchers have suggested that differences in cortical thickness may be related to internalizing symptoms, which typically increase during the same period. However, research has yielded inconclusive results. We utilized a new method that estimates the combined effect of individual differences in vertex-wise cortical thickness on internalizing symptoms. This approach allows for many small effects to be distributed across the cortex and avoids the necessity of correcting for multiple tests. Using a sample of 8763 children aged 8.9 to 11.1 from the ABCD study, we decomposed the total variation in caregiver-reported internalizing symptoms into differences in cortical thickness, additive genetics, and shared family environmental factors and unique environmental factors. Our results indicated that individual differences in cortical thickness accounted for less than 0.5% of the variation in internalizing symptoms. In contrast, the analysis revealed a substantial effect of additive genetics and family environmental factors on the different components of internalizing symptoms, ranging from 06% to 48% and from 0% to 34%, respectively. Overall, while this study found a minimal association between cortical thickness and internalizing symptoms, additive genetics, and familial environmental factors appear to be of importance for describing differences in internalizing symptoms in late childhood. RESEARCH HIGHLIGHTS: We utilized a new method for modelling the total contribution of vertex-wise individual differences in cortical thickness to internalizing symptoms in late childhood. The total contribution of individual differences in cortical thickness accounted for <0.5% of the variance in internalizing symptoms. Additive genetics and shared family environmental variation accounted for 17% and 34% of the variance in internalizing symptoms, respectively. Our results suggest that cortical thickness is not an important indicator for internalizing symptoms in childhood, whereas genetic and environmental differences have a substantial impact.

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Childhood externalizing psychopathology is heterogeneous. Symptom variability in conduct disorder (CD), oppositional defiant disorder (ODD), attention-deficit/hyperactivity disorder (ADHD), and callous-unemotional (CU) traits designate different subgroups of children with externalizing problems who have specific treatment needs. However, CD, ODD, ADHD, and CU traits are highly comorbid. Studies need to generate insights into shared versus unique risk mechanisms, including through the use of functional magnetic resonance imaging (fMRI). In this study, we tested whether symptoms of CD, ODD, ADHD, and CU traits were best represented within a bifactor framework, simultaneously modeling shared (i.e., general externalizing problems) and unique (i.e., symptom-specific) variance, or through a four-correlated factor or second-order factor model. Participants ( = 11,878, age, = 9 years) were from the Adolescent Brain and Cognitive Development Study. We used questionnaire and functional magnetic resonance imaging data (emotional N-back task) from the baseline assessment. A bifactor model specifying a general externalizing and specific CD, ODD, ADHD, and CU traits factors demonstrated the best fit. The four-correlated and second-order factor models both fit the data well and were retained for analyses. Across models, reduced right amygdala activity to fearful faces was associated with more general externalizing problems and reduced dorsolateral prefrontal cortex activity to fearful faces was associated with higher CU traits. ADHD scores were related to greater right nucleus accumbens activation to fearful and happy faces. Results give insights into risk mechanisms underlying comorbidity and heterogeneity within externalizing psychopathology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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Disentangling the molecular underpinnings of major depressive disorder (MDD) is necessary for identifying new treatment and prevention targets. The functional impact of depression-related transcriptomic changes on the brain remains relatively unexplored. We recently developed a novel transcriptome-based polygenic risk score (tPRS) composed of genes transcriptionally altered in MDD. Here, we sought to investigate effects of tPRS on brain structure in a developmental cohort (Adolescent Brain Cognitive Development study; n = 5124; 2387 female) at baseline (9-10 years) and 2-year follow-up (11-12 years). We tested associations between tPRS and Freesurfer-derived measures of cortical thickness, cortical surface area, and subcortical volume. Across the whole sample, higher tPRS was significantly associated with thicker left posterior cingulate cortex at both baseline and 2-year follow-up. In females only, tPRS was associated with lower right hippocampal volume at baseline and 2-year follow-up, and lower right pallidal volume at baseline. Furthermore, regional subcortical volume significantly mediated an indirect effect of tPRS on depressive symptoms in females at both timepoints. Conversely, tPRS did not have significant effects on cortical surface area. These findings suggest the existence of a sex-specific neurodevelopmental signature associated with shifts towards a more depression-like brain transcriptome, and highlight novel pathways of developmentally mediated MDD risk.

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To investigate relationships among different physical health problems in a large, sociodemographically diverse sample of 9-to-10-year-old children and determine the extent to which perinatal health factors are associated with childhood physical health problems.

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Though research indicates that certain aspects of adverse neighborhood conditions may influence weight development in childhood and adolescence, it is unknown if the Child Opportunity Index (COI), a composite measure of 29 indicators of neighborhood conditions, is associated with weight outcomes in adolescence. We hypothesized that lower COI would be associated with higher overweight and obesity in cross-sectional and longitudinal modeling in a national sample of 9 year olds and 10 year olds and that this association would be different by sex.

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Digital media (DM) takes an increasingly large part of children’s time, yet the long-term effect on brain development remains unclear. We investigated how individual effects of DM use (i.e., using social media, playing video games, or watching television/videos) on the development of the cortex (i.e., global cortical surface area), striatum, and cerebellum in children over 4 years, accounting for both socioeconomic status and genetic predisposition. We used a prospective, multicentre, longitudinal cohort of children from the Adolescent Brain and Cognitive Development Study, aged 9.9 years when entering the study, and who were followed for 4 years. Annually, children reported their DM usage through the Youth Screen Time Survey and underwent brain magnetic resonance imaging scans every 2 years. Quadratic-mixed effect modelling was used to investigate the relationship between individual DM usage and brain development. We found that individual DM usage did not alter the development of cortex or striatum volumes. However, high social media usage was associated with a statistically significant change in the developmental trajectory of cerebellum volumes, and the accumulated effect of high-vs-low social media users on cerebellum volumes over 4 years was only β = - 0.03, which was considered insignificant. Nevertheless, the developmental trend for heavy social media users was accelerated at later time points. This calls for further studies and longer follow-ups on the impact of social media on brain development.

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Previous work has found increased endorsement of psychotic-like experiences (PLEs) among marginalized racial and ethnic groups. According to social determinants frameworks, marginalized groups are at increased risk for exposure to socio-environmental risk factors, including systemic factors (e.g., poverty and poor housing conditions), and social stressors (e.g., discrimination). We examine the extent to which environmental risk factors and stress account for associations between racial/ethnic groups with PLEs.

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Persistence and distress distinguish more clinically significant psychotic-like experiences (PLEs) from those that are less likely to be associated with impairment and/or need for care. Identifying risk factors that differentiate clinically relevant PLEs early in development is important for improving our understanding of the etiopathogenesis of these experiences. Machine learning analyses examined the most important baseline factors distinguishing persistent distressing PLEs.

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Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear.

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To assess the prevalence of various media parenting practices and identify their associations with early adolescent screen time and problematic social media, video game, and mobile phone use.

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