DESCRIPTION (provided by applicant): 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. In response to RFA- DA-15-015, this application proposes the University of Pittsburgh Research Project Site component [12/13] of the Adolescent Brain Cognitive Development (ABCD)-USA consortium to prospectively determine the neurodevelopmental and behavioral effects of substance on children and adolescents. In Pittsburgh, a representative community sample of 550 9-10 year old substance-naïve children will be recruited (total ABCD- USA n=11,111 from 11 total sites) and will undergo a baseline assessment and two to three follow-ups over a five year period. At each assessment period, participants will undergo state-of-the-art brain imaging, comprehensive neuropsychological testing, and extensive assessment of substance use patterns and mental health functioning. The brain, behavioral, psychological, social, genetic, and environmental data collected during the course of this project will elucidate: 1) the effects o 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: In addition, ABCD-USA Pittsburgh will provide a unique focus determining how the cognitive dimensions of working memory and inhibitory control and the maturation of corticostriatal systems can inform our understanding of the risks for and effects of early adolescent marijuana use. Working memory and inhibitory control improve during adolescence in parallel with maturation of underlying corticostriatal neurocircuitry. An understanding of these areas of adolescent brain and cognitive development provide critical information in models determining vulnerabilities for and consequences of marijuana and other substance use. In Y03, Pittsburgh will focus on analyses examining working memory and inhibitory control phenotypes and neurodevelopmental characteristics prior to substance use. In Y04-Y05, these neurocognitive characteristics will be examined as risks for early adolescent marijuana use trajectories and, in Y10, accelerated adolescent marijuana use trajectories. Machine Learning will be applied to integrating cognitive and neuroimaging features to characterize a model of risks for early adolescent marijuana use.

PUBLIC HEALTH RELEVANCE: The ABCD-USA Consortium will use multimodal brain imaging, cognitive and clinical assessments, bioassays, mobile monitoring, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning in 11,111 adolescents followed over 10 years to determine the effects of substance use on adolescent brain and cognitive development. Our 12/13 ABCD-USA Consortium: Research Project will recruit and assess 550 youth age 9-10 at project entry. In addition to contributions to the overall consortium, our U01 will specifically focus on the effects of adolescent marijuana use on working memory, inhibitory control and corticostriatal systems.