PROJECT SUMMARY Substance use during early adolescence is associated with a variety of adverse outcomes. Early adolescents often initiate use of more than one substance (i.e., polysubstance use), which increases their risk for negative outcomes, including adult substance use disorders, mental health disorders, and social and legal problems. However, few studies have identified patterns of polysubstance use among early adolescents. There is a critical gap in knowledge of how polysubstance use develops during early adolescence and risk and protective factors for polysubstance use. There is clear evidence that early adolescents’ substance use co-occurs with externalizing behaviors, including physical aggression and delinquent behavior. What is less clear is the extent to which engaging in externalizing behaviors predicts subsequent changes in substance use, or whether substance use predicts changes in externalizing behaviors. Moreover, few studies have tested theoretical mechanisms that may explain these relations. The goal of the proposed study is to address limitations of prior research by identifying subgroups representing patterns of early adolescents’ polysubstance use, establishing their transitions over time, and examining their concurrent and longitudinal bidirectional relations with physical aggression and delinquency. The proposed study will also explore peer and caregiver factors as potential mediators of these relations. These goals align with NIDA’s goal of identifying causes and consequences of substance use, and priority focus (Theme 3) of addressing real-world complexities of substance use, including polydrug use and co-occurring health conditions. The aims will be addressed through analysis of 4 waves of data that were collected every 3 months from a primarily African American sample of 2,755 early adolescents living in urban communities with high rates of poverty and violence. Latent transition analysis and longitudinal cross-lagged structural equation models will be used to examine changes over time. The specific aims are to: 1) Examine longitudinal changes in polysubstance use patterns within and across all three middle school grades, 2) Evaluate concurrent and longitudinal bidirectional relations between physical aggression and delinquency and polysubstance use patterns, and 3) Explore peer delinquency and caregiver knowledge as mediators or predictors of adolescents’ externalizing and substance use behaviors over time. Differences across sex and grade will be examined for each aim. The findings will inform prevention efforts by refining our understanding of risk for early polysubstance use, potentially highlighting optimal intervention periods, and identifying possible intervention targets. Moreover, the research and training outlined in this NRSA F31 pre- doctoral fellowship application will equip the applicant with skills and mentoring needed to pursue an independent research career, including knowledge of factors that impact...