Youth Team Sports Participation Associates With Reduced Dimensional Psychopathology Through Interaction With Biological Risk Factors.

Background: Physical activity is associated with mental health benefits in youth. Here, we used causal inference and triangulation with 2 levels of biology to substantiate relationships between sports participation and dimensional psychopathology in youths. Methods: Baseline data from the Adolescent Brain Cognitive Development (ABCD) Study, which recruited children from 9 to 10 years of age across the United States, were included in multilevel regression models to assess relationships between lifetime participation in team sports (TS), individual sports, and nonsports activities and Child Behavior Checklist (CBCL) scores. We calculated polygenic risk scores for 8 psychiatric disorders to assess interactions with sports exposure on CBCL scores among European descendants. Following rigorous quality control, FreeSurfer-extracted brain magnetic resonance imaging structural data were examined for mediation of CBCL-activities relationships. Results: Among those with complete data (N = 10,411), causal estimates using inverse probability weighting associated lifetime TS exposure with a 1.05-point reduction in CBCL total (95% CI, -1.54 to -0.56, p < .0001) a relationship that was specific to TS and strengthened with more years of exposure. Associations of attention-deficit/hyperactivity disorder polygenic loading with CBCL total weakened in European children with TS exposure (n = 4041; beta = -0.93, SE = 0.38, p = .013). Furthermore, TS participation and lower CBCL each associated with increased subcortical volumes (n = 8197). Subcortical volume mediated 5.5% of TS effects on CBCL total. Conclusions: Our findings support prior associations of TS participation with lower psychopathology in youths through additional studies that demonstrate specificity, dose response, and coherence across 2 levels of biology. Longitudinal studies that further clarify causal relationships may justify interventional studies of TS for high-risk youth.

Genetic patterning for child psychopathology is distinct from that for adults and implicates fetal cerebellar development.

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

Uncovering and mitigating bias in large, automated MRI analyses of brain development.

Large, population-based MRI studies of adolescents promise transformational insights into neurodevelopment and mental illness risk 1,2. However, MRI studies of youth are especially susceptible to motion and other artifacts 3,4. These artifacts may go undetected by automated quality control (QC) methods that are preferred in high-throughput imaging studies, 5 and can potentially introduce non-random noise into clinical association analyses. Here we demonstrate bias in structural MRI analyses of children due to inclusion of lower quality images, as identified through rigorous visual quality control of 11,263 T1 MRI scans obtained at age 9-10 through the Adolescent Brain Cognitive Development (ABCD) Study6. Compared to the best-rated images (44.9% of the sample), lower-quality images generally associated with decreased cortical thickness and increased cortical surface area measures (Cohen's d 0.14-2.84). Variable image quality led to counterintuitive patterns in analyses that associated structural MRI and clinical measures, as inclusion of lower-quality scans altered apparent effect sizes in ways that increased risk for both false positives and negatives. Quality-related biases were partially mitigated by controlling for surface hole number, an automated index of topological complexity that differentiated lower-quality scans with good specificity at Baseline (0.81-0.93) and in 1,000 Year 2 scans (0.88-1.00). However, even among the highest-rated images, subtle topological errors occurred during image preprocessing, and their correction through manual edits significantly and reproducibly changed thickness measurements across much of the cortex (d 0.15-0.92). These findings demonstrate that inadequate QC of youth structural MRI scans can undermine advantages of large sample size to detect meaningful associations.

Association of adverse prenatal exposure burden with child psychopathology in the Adolescent Brain Cognitive Development (ABCD) Study.

OBJECTIVE: Numerous adverse prenatal exposures have been individually associated with risk for psychiatric illness in the offspring. However, such exposures frequently co-occur, raising questions about their cumulative impact. We evaluated effects of cumulative adverse prenatal exposure burden on psychopathology risk in school-aged children. METHODS: Using baseline surveys from the U.S.-based Adolescent Brain and Cognitive Development (ABCD) Study (7,898 non-adopted, unrelated children from 21 sites, age 9-10, and their primary caregivers), we examined 8 retrospectively-reported adverse prenatal exposures in relation to caregiver-reported total and subscale Child Behavior Checklist (CBCL) scores. We also assessed cumulative effects of these factors on CBCL total as a continuous measure, as well as on odds of clinically significant psychopathology (CBCL total ≥60), in both the initial set and a separate ABCD sample comprising an additional 696 sibling pairs. Analyses were conducted before and after adjustment for 14 demographic and environmental covariates. RESULTS: In minimally and fully adjusted models, 6 exposures (unplanned pregnancy; maternal alcohol, marijuana, and tobacco use early in pregnancy; pregnancy complications; and birth complications) independently associated with significant but small increases in CBCL total score. Among these 6, none increased the odds of crossing the threshold for clinically significant symptoms by itself. However, odds of exceeding this threshold became significant with 2 exposures (OR = 1.86, 95% CI 1.47-2.36), and increased linearly with each level of exposure (OR = 1.39, 95% CI 1.31-1.47), up to 3.53-fold for ≥4 exposures versus none. Similar effects were observed in confirmatory analysis among siblings. Within sibling pairs, greater discordance for exposure load associated with greater CBCL total differences, suggesting that results were not confounded by unmeasured family-level effects. CONCLUSION: Children exposed to multiple common, adverse prenatal events showed dose-dependent increases in broad, clinically significant psychopathology at age 9-10. Fully prospective studies are needed to confirm and elaborate upon this pattern.