PROJECT SUMMARY / ABSTRACT. Substance use disorders affect millions of Americans, with substance use often beginning in adolescence. There is a pressing need to identify targets for interventions that reduce substance use initiation and misuse, especially for those at high risk. Our primary goal is to examine adolescent music engagement as a potential protective factor for early substance use behaviors. Music engagement is promising because of its many prosocial benefits, including for quality of life, social connectedness, and emotional competence. However, existing studies have not evaluated whether associations between music engagement and substance use are driven by correlated genetic or environmental influences versus direct causal effects. Beyond this, gene-by- environment interactions (GxE) are highly relevant to both music engagement and substance use, and music engagement may be especially protective for individuals at high genetic or environmental risk for substance use. Establishing these associations and understanding whether they are specific to music engagement and/or may be observed for other activities (e.g., art, sports engagement) will inform translational and intervention efforts aimed at preventing or reducing adolescent substance use before problematic use. We will conduct secondary data analyses of large longitudinal twin/family studies with multiple waves of assessment of music engagement, substance use, and genotyping on most subjects. Datasets include the Adolescent Brain Cognitive Development Study (ABCD) and the Colorado Adoption/Twin Study of Lifespan Behavioral Development and Cognitive Aging (CATSLife). Analyses include multiple twin/family and genomic approaches that inform whether associations are due to a combination of genetic, environmental, and causal effects (e.g., Mendelian Randomization Direction of Causation, Aim 1a), longitudinal analyses examining whether music engagement predicts later substance use behaviors (Aim 1b), and a detailed comparison of music engagement with other activities (Aim 1c). We will also test competing theoretical models of GxE (diathesis stress versus differential susceptibility) using polygenic scores (Aim 2a), environmental risk variables (e.g., SES, peer use, Aim 2b), and socio-demographic measures (Aim 2c). The study team is well-versed in longitudinal structural equation modeling approaches to study substance use and music engagement, including polygenic score and twin/family approaches leveraged here (and combinations of both). The research supported by this R01 award will be critical for understanding how music engagement relates to adolescent substance use initiation and progression, and to quantify the nature of these associations. It will lay groundwork for music intervention studies targeting individuals at highest risk for substance use problems (e.g., polygenic scores, environmental risk factors). This work responds directly to NIDA’s mission to identify factors leading to the prevention of substance use disorder and is directly relevant to the Music and Health initiative’s goal to examine how music engagement relates to important health traits such as substance use.

PROJECT NARRATIVE: Our goal is to better understand the emergence of adolescent substance use behaviors by testing the hypothesis that music engagement is associated with less substance use initiation and less frequent substance use. There is already evidence that music engagement interventions are effective for individuals with substance use disorders, and there are multiple reasons to expect these beneficial effects could extend to substance initiation in adolescence. By integrating state-of-the art genetic and longitudinal approaches that address key confounds, this work will quantify these potentially protective associations and provide critical groundwork for translational and intervention efforts targeted at supporting high-risk individuals before the onset of problematic substance use.