Project Summary/Abstract Problematic alcohol use is a growing public health concern that typically begins during adolescence/young adulthood. Typical brain maturation patterns wherein emotion- and reward-related regions are prioritized over those relevant to cognitive control and regulation have been linked to developmental risk for alcohol involvement as well as neurotoxic effects of alcohol. The extent to which alcohol involvement results from individual differences in genomically-conferred brain development and related behavioral phenotypes and/or modifies neural trajectories and behavior is not clear. Longitudinal, genetically informed research can address these questions by examining developmental trajectories of alcohol involvement and related risks and consequences. The overarching aim of this investigation is to examine: (a) whether polygenic vulnerability to stage-based behavioral and structural neural phenotypes are related to trajectories of alcohol involvement (i.e., initiation, escalation, problematic use, desistance) from late childhood through young adulthood, and (b) the extent to which these behavioral and neural indicators share genomic liability with stages of alcohol involvement. Through the use of state-of-the-art genomic techniques and the integration of three well-powered, longitudinal datasets with idiosyncratic strengths alongside several genome-side association studies of alcohol involvement, brain structure, and behavior, this multimodal, interdisciplinary investigation aims to yield novel insights about biological and behavioral mechanisms underlying and transacting with alcohol involvement trajectories. Results from the proposed project have the potential to inform the etiologic conceptualization of adolescent and young adult alcohol involvement and improve prevention and treatment as well as relevant policy and educational efforts. The realization of this project will be achieved through the following training goals: (1) to acquire expert knowledge about alcohol involvement and related brain structure and behavior, (2) to promote competence in advance quantitative (e.g., longitudinal) analysis, (3) to gain training in cutting-edge genomic methodology, (4) to augment familiarity with methods of structural neuroimaging, and (5) to promote professional development as the applicant progresses toward a career as an independent, NIH-funded academic researcher. The training team assembled to assist the applicant in achieving these goals has substantial expertise in alcohol use trajectories, brain structure, and longitudinal and genomic techniques. With their support, the applicant will develop the phenotypic, analytic, and professional aptitude needed to foster her research program and career ambitions.

Project Narrative Adolescent alcohol involvement is prevalent, deleterious, and arises in the context of uneven neural maturation that prioritizes reward over regulation. This proposal seeks to investigate how heritable neural and behavioral factors promote risk for and are influenced by the initiation, escalation, and problematic alcohol from middle childhood through young adulthood. The overarching goal of this line of research is to better elucidate these etiological and interactive developmental processes of alcohol involvement to ultimately inform clinical, community, and policy-based efforts to prevent and treat alcohol use disorder and related problems.