Adolescence is a critical neurodevelopmental period that is associated with dramatic increases in rates of substance use. Identifying predictors of substance use and its effects on child and adolescent development is critically important, as substance-related decrements incurred during ongoing maturation could have long- lasting effects on brain functioning and behavioral, health, and psychological outcomes. This Research Project Site application from the University of Michigan and University of Florida is in response to RFA-DA-15-015, as part of the ABCD-USA Consortium (9/13) to prospectively determine the neurodevelopmental and behavioral effects of substance use on children and adolescents. A representative community sample of 975 9-10 year olds will be recruited as part of this application, contributing to the sample of 11,111 to be collected from 11 total sites across the ABCD-USA Consortium. All participants will undergo a comprehensive baseline assessment, including state-of-the-art brain imaging, comprehensive neuropsychological testing, and extensive assessment of substance use patterns and mental health functioning. These comprehensive assessments will occur at 2-year follow-up intervals, with intermediate assessments of functioning and substance use at 6- month intervals. The brain, behavioral, psychological, social, genetic, and environmental data collected during the course of this project will elucidate: 1) the effects of substance use patterns on the adolescent brain; 2) the effects of substance use on behavioral and health outcomes; 3) the bidirectional relationship between psychopathology and substance use patterns; 4) the effects of individual genetic, behavioral, neurobiological, and environmental differences on risk profiles and substance use outcomes; and 5) the gateway interactions between use of different substances. Elements Unique to this Site: This hub's Research Project application leverages site-specific expertise to address two aims focused on the identification of risk and resilience factors for adolescent substance use. Using baseline data categorized into distinct domains (Demographic, Cognitive, Mental Health, Personality, Life Stressors, Family History/Genetics, Environmental, and Brain), we will use cutting-edge, multi-stage analytic methods involving data reduction within each domain (e.g., latent variable analyses), identification of etiologically-distinct subgroups (e.g., community detection), and the construction of integrated multi-modal predictive models (e.g., regularized regression). This approach will delineate subgroups characterized by distinct profiles of risk and resilience. This approach is essential for informing outcomes of substance use during adolescence, which will ultimately inform the development of more efficacious interventions and clarify the toxic effects of exposure on adolescent brain, health, and cognition.