Individual Trajectories of Depressive Symptoms Within Racially-Ethnically Diverse Youth: Associations with Polygenic Risk for Depression and Substance Use Intent and Perceived Harm.

There are distinct individual trajectories of depressive symptoms across adolescence which are most often differentiated into low, moderate/stable, and high/increasing groups. Research has found genetic predisposition for depression associated with trajectories characterized by greater depressive symptoms. However, the majority of this research has been conducted in White youth. Moreover, a separate literature indicates that trajectories with elevated depressive symptoms can result in substance use. It is critical to identify depressive symptom trajectories, genetic predictors, and substance use outcomes in diverse samples in early adolescence to understand distinct processes and convey equitable benefits from research. Using data from the Adolescent Cognitive Brain Development Study (ABCD), we examined parent-reported depressive symptom trajectories within Black/African American (AA, n = 1783), White/European American (EA, n = 6179), and Hispanic/Latinx (LX, n = 2410) youth across four annual assessments in early adolescence (age 9-10 to 12-13). We examined racially/ethnically aligned polygenic scores (Dep-PGS) as predictors of trajectories as well as substance use intent and perceived substance use harm as outcomes at age 12-13. Differential trajectories were found in AA, EA, and LX youth but low and high trajectories were represented within each group. In EA youth, greater Dep-PGS were broadly associated with membership in trajectories with greater depressive symptoms. Genetic effects were not significant in AA and LX youth. In AA youth, membership in the low trajectory was associated with greater substance use intent. In EA youth, membership in trajectories with higher depressive symptoms was associated with greater substance use intent and less perceived harm. There were no associations between trajectories and substance use intent and perceived harm in LX youth. These findings indicate that there are distinct depressive symptom trajectories in AA, EA, and LX youth, accompanied by unique associations with genetic predisposition for depressive symptoms and substance use outcomes.

Genetic influences on the interplay between obsessive-compulsive behavior symptoms and cannabis use during adolescence.

INTRODUCTION: There are overlapping biological origins and behaviors associated with obsessive-compulsive symptoms (OCS) and cannabis use. There is also evidence that OCS and cannabis use are associated over time. Thus, we investigated polygenic predisposition for OCS as predictive of OCS and cannabis use from age 17 to 19. We hypothesized that greater genetic risk for OCS would predict both OCS and cannabis use. METHODS: The current study used participants from the Project Alliance 1 study, a US-based sample, for whom genomic, OCS, and cannabis use data were available (n = 547). Polygenic risk scores (PRS) were formed via a meta-genome-wide association study on OCS and examined as a predictor of OCS and cannabis use at age 17 and 19. The sample was diverse (52.4% male; 45% European American, 30% African American, 14% multiracial, 5% Hispanic/Latino, 4% Asian American, and 2% other groups). Sensitivity analysis was performed by gender for European American and African American subsamples. RESULTS: Across the whole sample, the greater polygenic risk for OCS was negatively associated with cannabis use at age 17 and positively associated with OCS at 19. Cannabis use at age 17 was positively associated with OCS at age 19. The association between polygenic risk for OCS and cannabis use at age 17 was replicated in European American males, whereas the association between cannabis use at age 17 and OCS at age 19 was replicated in African American males. CONCLUSIONS: Cannabis use may exacerbate OCS through adolescence, and genetic predisposition for OCS may be associated with lower cannabis use in efforts to avoid exacerbation of OCS.

Polygenic Risk for Aggression Predicts Adult Substance Use Disorder Diagnoses via Substance Use Offending in Emerging Adulthood and is Moderated by a Family-Centered Intervention.

A substance use offense reflects an encounter with law enforcement and the court system in response to breaking the law which may increase risk for substance use problems later in life. Individuals may also be at risk for substance use offending and substance use problems based on genetic predisposition. We examined a mediation model in which polygenic risk for aggression predicted adult substance use disorder diagnoses (SUD) via substance use offending in emerging adulthood. In addition, we explored for potential attenuation of genetic influences on these outcomes by a family-based intervention, the Family Check-Up (FCU). Secondary data analyses based upon the Project Alliance 1 sample was conducted among those with genetic data (n = 631; 322 from control and 309 from FCU intervention). The sample was ethnically diverse (30% African American, 44% European American, 6% Latinx, 4% Asian American, 3% Native American, and 13% Other). Greater polygenic risk for aggression was found to increase risk for substance use violations (age 19-23), which in turn was associated with greater likelihood of being diagnosed with SUD at age 27. A gene-by-intervention effect was found in which individuals in the control group had greater risk for SUD with increasing polygenic risk for aggression. Some convergence in results was found when replicating analyses in African American and European American subgroups. Results imply that genetic predisposition may increase risk for problematic substance use later in life via antisocial behavior, such as substance use offending, and that this can be attenuated by a family-centered intervention.

Polygenic Effects on Individual Rule Breaking, Peer Rule Breaking, and Alcohol Sips Across Early Adolescence in the ABCD Study.

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