Examining polygenic scores for depression, depressive symptoms from childhood to adolescence, and adolescent substance use in a diverse sample: The moderating impact of a family-centered intervention

Research finds genetic predisposition for depression is associated with increases in depression across adolescence and adulthood. In turn, depressive symptoms in adolescence are associated with substance use. However, there has been modest examination of genetic predisposition for depression, growth in depressive symptoms, and substance use from late childhood through adolescence, and mostly in White samples. Also, psychosocial interventions can attenuate associations between genetic predisposition and psychopathology, a genotype by intervention (GxI) effect. We examined associations among polygenic risk for depression, growth in depressive symptoms from age 7 to 16, and substance use at age 16, as well as moderation by a family-based preventive intervention. Participants were African-ancestry (<i>n</i> = 154) and European-ancestry (<i>n</i> = 219) youth from the Early Steps Multisite Study, half of whom participated in the Family Check-Up intervention. A small polygenic by intervention effect was found on reductions in depressive symptoms for African-ancestry youth, and growth in depressive symptoms was positively associated with substance use at age 16. In sensitivity analyses, a small GxI effect was detected in European-ancestry youth on reductions in depressive symptom slopes from age 10 to 16. These findings highlight how early intervention can buffer genetic effects on depressive symptoms over time.