Evaluation of environmental-genetic factors and mental health outcomes for sleep disturbance from late childhood to early adolescence.

ADHD: The Mammoth Task of Disentangling Genetic, Environmental, and Developmental Risk Factors.

<h3>Background</h3> Exposure to parental mental ill-health and poverty may impact child health problems across the life course. Although both maternal and paternal caregiver mental health may be important, few studies have unpicked the complex interrelationships between these exposures and family poverty. We therefore assessed the lifecourse mental health and poverty trajectories of caregivers and their impacts on the health of the next generation at the point of transition to adulthood. <h3>Methods</h3> We used longitudinal data from the nationally representative UK Millennium Cohort study on 10500 children born between 2000 and 2002, followed through seven survey waves. Trajectories of poverty, caregiver and partner mental health were constructed from child age 9 months through to 14 years, adjusting for lone parenthood status. We assessed associations of these trajectories with socioemotional behavioural problems, cognitive disability and mental health problems at age 17 years using multivariable logistic regression whilst adjusting for confounders. <h3>Results</h3> We identified five distinct trajectories: low poverty and good parental mental health (47%), persistent poor caregiver mental health (11%), persistent poor partner mental health (9%), persistent poverty (22%), and persistent poverty and poor parental mental health (11%). Compared with children exposed to low poverty and good parental mental health, those who experienced the combination of poverty, poor caregiver and partner mental health were at increased risk of socioemotional behavioural problems (adjusted odds ratio 4·2; 95% CI 2·7 – 6·7), mental health problems (aOR 2·5; CI 1·6 – 3·9) and cognitive disability (aOR 1·7; CI 1·1 – 2·5) at age 17. The associations were of similar magnitude when comparing the analyses by caregiver and partner status. <h3>Conclusion</h3> Both caregiver and partner mental health co-occur with family poverty with more than 50% of children in the UK exposed to some degree of poverty and/or parental mental health problems. The combination of these exposures is strongly associated with adverse mental and behavioural health outcomes in the next generation, and requires public health attention.

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

Alcohol use during adolescence poses a significant public health problem due to its potential long-term consequences on both physical and mental health and increased risk for developing substance use disorders later in life. Both individual (e.g., genetic liability, neural functioning, personality features) and environmental (e.g., parenting, school environment) features play an important role in accelerating or buffering the progression of early alcohol consumption. This study used data from the Adolescent Brain Cognitive Development (ABCD) study (Release 5.1; N = 11,868) to provide a comprehensive examination of how genetic, neural, trait, and environmental factors are associated with risk for first sip of alcohol, first full drink, and the progression from first sip to full drink, both independently and uniquely. Cox proportional hazard models were used to examine the univariable associations between theoretically relevant genetic, neural, trait, and environmental variables and early alcohol use. Then, stepwise model-fitting was used to determine which indicators were uniquely associated with alcohol outcomes. Risk for early alcohol use was distributed across multiple domains highlighting the unique information provided by genetic, trait, and environmental variables. Results also indicated the importance of both environmental and genetic factors on time to first sip of alcohol, but that time to first full drink and the progression from sip to drink was most associated with genetic and trait factors rather than broad environmental influences. These findings highlight both potential etiological pathways driving early alcohol use as well as phenotypic and environmental process that can be targeted for early intervention efforts.

Adolescence is a period of significant brain development and maturation, and it is a time when many mental health problems first emerge. This study aimed to explore a comprehensive map that describes possible pathways from genetic and environmental risks to structural brain organization and psychopathology in adolescents. We included 32 environmental items on developmental adversity, maternal substance use, parental psychopathology, socioeconomic status (SES), school and family environment; 10 child psychopathological scales; polygenic risk scores (PRS) for 10 psychiatric disorders, total problems, and cognitive ability; and structural brain networks in the Adolescent Brain Cognitive Development study (ABCD, n = 9168). Structural equation modeling found two pathways linking SES, brain, and psychopathology. Lower SES was found to be associated with lower structural connectivity in the posterior default mode network and greater salience structural connectivity, and with more severe psychosis and internalizing in youth (p < 0.001). Prematurity and birth weight were associated with early-developed sensorimotor and subcortical networks (p < 0.001). Increased parental psychopathology, decreased SES and school engagement was related to elevated family conflict, psychosis, and externalizing behaviors in youth (p < 0.001). Increased maternal substance use predicted increased developmental adversity, internalizing, and psychosis (p < 0.001). But, polygenic risks for psychiatric disorders had moderate effects on brain structural connectivity and psychopathology in youth. These findings suggest that a range of genetic and environmental factors can influence brain structural organization and psychopathology during adolescence, and that addressing these risk factors may be important for promoting positive mental health outcomes in young people.

PurposeExposure to parental mental ill-health and poverty in childhood impact health across the lifecourse. Both maternal and paternal mental health may be important influences, but few studies have unpicked the complex interrelationships between these exposures and family poverty for later health. MethodsWe used longitudinal data on 10,500 children from the nationally representative UK millennium cohort study. Trajectories of poverty, maternal mental health, and secondary caregiver mental health were constructed from child age of 9 months through to 14 years. We assessed the associations of these trajectories with mental health outcomes at the age of 17 years. Population-attributable fractions were calculated to quantify the contribution of caregivers' mental health problems and poverty to adverse outcomes at the country level. ResultsWe identified five distinct trajectories. Compared with children with low poverty and good parental mental health, those who experienced poverty and poor primary or secondary caregiver mental health (53%) had worse outcomes. Children exposed to both persistent poverty and poor caregiver mental health were at markedly increased risk of socioemotional behavioural problems (aOR 4.2; 95% CI 2.7–6.7), mental health problems (aOR 2.5; CI 1.6–3.9), and cognitive disability (aOR 1.7; CI 1.1–2.5). We estimate that 40% of socioemotional behavioural problems at the age of 17 were attributable to persistent parental caregivers' mental health problems and poverty. DiscussionMore than half of children growing up in the UK are persistently exposed to either one or both of poor caregiver mental health and family poverty. The combination of these exposures is strongly associated with adverse health outcomes in the next generation.

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. To quantify the aggregate contribution of environmental and lifestyle factors to youth suicide attempt risk classification. This was a cohort study in 3 youth samples: 2 national longitudinal cohorts from the US and the UK and 1 clinical cohort from a tertiary pediatric US hospital. An exposome-wide association study (ExWAS) approach was used to identify risk and protective factors and compute aggregate exposomic scores. Logistic regression models were applied to test associations and model fit of exposomic scores with suicide attempts in independent data. Youth from the Adolescent Brain Cognitive Development (ABCD) study, the UK Millennium Cohort Study (MCS), and the Children's Hospital of Philadelphia emergency department (CHOP-ED) were included in the study. A single-weighted exposomic score that sums significant risk and protective environmental/lifestyle factors. Self-reported suicide attempt. A total of 40 364 youth were included in this analysis: 11 564 from the ABCD study (3 waves of assessment; mean [SD] age, 12.0 [0.7] years; 6034 male [52.2%]; 344 attempted suicide [3.0%]; 1154 environmental/lifestyle factors were included in the ABCD study), 9000 from the MCS cohort (mean [SD] age, 17.2 [0.3] years; 4593 female [51.0%]; 661 attempted suicide [7.3%]; 2864 environmental/lifestyle factors were included in the MCS cohort), and 19 800 from the CHOP-ED cohort (mean [SD] age, 15.3 [1.5] years; 12 937 female [65.3%]; 2051 attempted suicide [10.4%]; 36 environmental/lifestyle factors were included in the CHOP-ED cohort). In the ABCD discovery subsample, ExWAS identified 99 risk and protective exposures significantly associated with suicide attempt. A single weighted exposomic score that sums significant risk and protective exposures was associated with suicide attempt in an independent ABCD testing subsample (odds ratio [OR], 2.2; 95% CI, 2.0-2.6; P < .001) and explained 17.6% of the variance (based on regression pseudo-R2) in suicide attempt over and above that explained by age, sex, race, and ethnicity (2.8%) and by family history of suicide (6.3%). Findings were consistent in the MCS and CHOP-ED cohorts (explaining 22.6% and 19.3% of the variance in suicide attempt, respectively) despite clinical, demographic, and exposure differences. In all cohorts, compared with youth at the median quintile of the exposomic score, youth at the top fifth quintile were substantially more likely to have made a suicide attempt (OR, 4.3; 95% CI, 2.6-7.2 in the ABCD study; OR, 3.8; 95% CI, 2.7-5.3 in the MCS cohort; OR, 5.8; 95% CI, 4.7-7.1 in the CHOP-ED cohort). Results suggest that exposomic scores of suicide attempt provided a generalizable method for risk classification that can be applied in diverse samples from clinical or population settings.

Sleep Disturbance Predicts Depression Symptoms in Early Adolescence: Initial Findings From the Adolescent Brain Cognitive Development Study

Acculturative Orientations Among Hispanic/Latinx Caregivers in the ABCD Study: Associations With Caregiver and Youth Mental Health and Youth Brain Function

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

Perceived Racism, Brain Development, and Internalizing and Externalizing Symptoms: Findings From the ABCD Study.

Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric disorders which result from complex interplay between genetic and environmental factors. It is well-established that they are highly heritable disorders, and considerable progress has been made identifying their shared and distinct genetic risk factors. However, the 15–40% of risk that is derived from environmental sources is less definitively known. Environmental factors that have been repeatedly investigated and often associated with SZ include: obstetric complications, infections, winter or spring birth, migration, urban living, childhood adversity, and cannabis use. There is evidence that childhood adversity and some types of infections are also associated with BD. Evidence for other risk factors in BD is weaker due to fewer studies and often smaller sample sizes. Relatively few environmental exposures have ever been examined for SZ or BD, and additional ones likely remain to be discovered. A complete picture of how genetic and environmental risk factors confer risk for these disorders requires an understanding of how they interact. Early gene-by-environment interaction studies for both SZ and BD often involved candidate genes and were underpowered. Larger samples with genome-wide data and polygenic risk scores now offer enhanced prospects to reveal genetic interactions with environmental exposures that contribute to risk for these disorders. Overall, although some environmental risk factors have been identified for SZ, few have been for BD, and the extent to which these account for the total risk from environmental sources remains unknown. For both disorders, interactions between genetic and environmental risk factors are also not well understood and merit further investigation. Questions remain regarding the mechanisms by which risk factors exert their effects, and the ways in which environmental factors differ by sex. Concurrent investigations of environmental and genetic risk factors in SZ and BD are needed as we work toward a more comprehensive understanding of the ways in which these disorders arise.

While adverse childhood experiences (ACEs) are known to impart significant risk for negative mental health and cognitive outcomes in youth, translation of ACE scores into clinical intervention is limited by poor specificity in predicting negative outcomes. This work expands on the ACE framework using a data-driven approach to identify 8 different forms of traumatic and adverse childhood experiences (TRACEs) and reveal their differential associations with psychiatric risk and cognition across development. Building upon the traditional ACEs model, this study aimed to characterize unique components of commonly co-occurring TRACEs and to examine moderation of longitudinal change in mental health and cognitive development during adolescence. This work draws from youth and their caregivers who completed up to 4 annual behavioral assessments from 2016 to 2021 as part of the ongoing Adolescent Brain Cognitive Development (ABCD) study. Data collection was performed at 21 regionally-distributed sites across the United States. Analyses for this work were conducted January 2023 through November 2023. Youth participants in the ABCD study's exposure to 268 different TRACEs, which were distilled into adversity components using nonlinear principal components analysis. Mixed-effects and latent change score models considered TRACEs components as moderators of longitudinal change in internalizing and externalizing mental health problems, as well as longitudinal change in cognitive ability. Data were distilled from 11 876 youth participants, who were grouped into dyads with a caregiver. ABCD study youth participants were 9 to 10 years old at baseline assessment (year 0) and 12 to 13 years old at ABCD year 3. A total of 5679 participants (47.8%) were female. Analyses revealed that TRACEs organized into 8 thematic adversity components (e.g., family conflict, interpersonal violence). At baseline assessment (year 0), exposure to nearly every adversity component was associated with poorer mental health and diminished cognitive ability. Yet across time, it was observed that different forms of adversity were variably linked to both increases and decreases in internalizing and externalizing problems. For example, while peer aggression (t = 5.31) and family conflict (t = 5.67) were associated with increases in both internalizing and externalizing problems over early adolescence, community threat (t = 2.82) and poverty (t = 2.07) were linked to decreased problems, potentially representing adaptive suppression of symptoms. Finally, adversity types related to resource deprivation (eg, poverty, caregiver maladjustment) were associated with declines in cognitive ability over early adolescence. In this cohort study, distinct forms of TRACEs differentially moderated developmental changes in psychiatric risk and cognitive ability in different ways, offering the possibility for precision-based prediction of risk for youth. Such findings could be used in targeted early prevention and intervention strategies for at-risk youth.

Brain imaging-derived structural correlates of alcohol involvement have largely been speculated to arise as a consequence of alcohol exposure. However, they may also reflect predispositional risk. In substance naïve children of European ancestry who completed the baseline session of the Adolescent Brain Cognitive Development (ABCD) Study (n=3013), mixed-effects models estimated whether polygenic risk scores (PRS) for problematic alcohol use (PAU-PRS) and drinks per week (DPW-PRS) are associated with magnetic resonance imaging-derived brain structure phenotypes (i.e., total and regional: cortical thickness, surface area and volume; subcortical volume; white matter volume, fractional anisotropy, mean diffusivity). Follow-up analyses evaluated whether any identified regions were also associated with polygenic risk among substance naïve children of African ancestry (n=898). After adjustment for multiple testing correction, polygenic risk for PAU was associated with lower volume of the left frontal pole and greater cortical thickness of the right supramarginal gyrus (|βs| > 0.009; ps < 0.001; psfdr < 0.046; r2 s < 0.004). PAU PRS and DPW PRS showed nominally significant associations with a host of other regional brain structure phenotypes (e.g., insula surface area and volume). None of these regions showed any, even nominal association among children of African ancestry. Genomic liability to alcohol involvement may manifest as variability in brain structure during middle childhood prior to alcohol use initiation. Broadly, alcohol-related variability in brain morphometry may partially reflect predisposing genomic influence. Larger discovery genome-wide association studies and target samples of diverse ancestries are needed to determine whether observed associations may generalize across ancestral origins.

Backgroundattention‐deficit/hyperactivity disorder (ADHD) is associated with both polygenic liability and environmental exposures, both intrinsic to the family, such as family conflict, and extrinsic, such as air pollution. However, much less is known about the interplay between environmental and genetic risks relevant to ADHD—a better understanding of which could inform both mechanistic models and clinical prediction algorithms.MethodsTwo independent data sets, the population‐based Adolescent Brain Cognitive Development Study (ABCD) (N = 11,876) and the case‐control Oregon‐ADHD‐1000 (N = 1449), were used to examine additive (G + E) and interactive (GxE) effects of selected polygenic risk scores (PRS) and environmental factors in a cross‐sectional design. Genetic risk was measured using PRS for nine mental health disorders/traits. Exposures included family income, family conflict/negative sentiment, and geocoded measures of area deprivation, lead exposure risk, and air pollution exposure (nitrogen dioxide and fine particulate matter).ResultsADHD PRS and family conflict jointly predicted concurrent ADHD symptoms in both cohorts. Additive‐effects models, including both genetic and environmental factors, explained significantly more variation in symptoms than any individual factor alone (joint R2 = .091 for total symptoms in ABCD; joint R2 = .173 in Oregon‐ADHD‐1000; all delta‐R2p‐values <2e‐7). Significant effect size heterogeneity across ancestry groups was observed for genetic and environmental factors (e.g., Q = 9.01, p = .011 for major depressive disorder PRS; Q = 13.34, p = .001 for area deprivation). GxE interactions observed in the full ABCD cohort suggested stronger environmental effects when genetic risk is low, though they did not replicate.ConclusionsReproducible additive effects of PRS and family environment on ADHD symptoms were found, but GxE interaction effects were not replicated and appeared confounded by ancestry. Results highlight the potential value of combining exposures and PRS in clinical prediction algorithms. The observed differences in risks across ancestry groups warrant further study to avoid health care disparities.