PROJECT SUMMARY This K23 award will allow Dr. Meruelo to become an expert on the relationship between adolescent alcohol use and depression. During his training, he proposes to address that untreated alcohol use disorder and depression lead to poor health outcomes ultimately affecting both quality and quantity of life. Dr. Meruelo plans to use an innovative approach and multiple imaging techniques of the NCANDA consortium in a longitudinal study to identify brain features that address the temporal relationship between these two comorbid disorders. Identifying risk factors is of critical importance to anticipating which individuals would benefit from earlier interventions and treatment to reduce morbidity and mortality directly. The award will provide him the support needed to develop expertise in four areas: (1) adolescent alcohol use and major depression, (2) neuroimaging and brain development, (3) advanced statistics, and (4) execution of longitudinal studies. To achieve the K23's goals, Dr. Meruelo has assembled an expert multidisciplinary team. Drs Tapert and Brown will facilitate guidance and access to the activities of and data from a longitudinal study conducted by the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) to address one of NIAAA's major initiatives. They will also provide expertise in adolescent alcohol use and comorbid depression and on planning, recruiting, and implementing longitudinal study designs with adolescents, as well as career and mentorship on the responsible conduct of research. Dr. Schuckit will provide expertise on comorbidity between alcohol and depression and other career development skills. Dr. Thomas will provide hands-on training in advanced longitudinal analyses of associated data. NCANDA data is already available to begin addressing central questions of the proposal. At Year 1 or 2, clinically significant depression has been identified in 61 participants after a healthy prior year following a non- depressed baseline. Also identified are those using moderate or heavy alcohol use at baseline, year 1, and year 2 of the study in 164, 223 and 283 participants, respectively. Year 3 data will be available January 2018. The K23 research specific aims are: (Aim 1) to identify whether any adolescent alcohol use is more likely to lead to long-term depression, or if long-term depression is seen more often after subsequent increases in alcohol use, or both, using latent difference score models to distinguish cause and effect. The common factor of stress and subsequent depression and/or substance use is critical to understanding their impact on growing adolescents, and (Aim 2) to identify morphometrics that predict the development of depression in healthy adolescents using: (a) Nave Bayesian classifier, and (b) principal component analysis with subsequent hierarchical linear regression.