PROJECT SUMMARY / ABSTRACT Alcohol use disorder (AUD) is highly heterogeneous in that its symptoms are highly varied and, often, non- overlapping across individuals. In theory, this phenotypic heterogeneity reflects the influence of multiple underlying causes, or etiologic mechanisms. This etiologic complexity makes AUD treatment very challenging; researchers have identified AUD’s etiologic complexity as the most critical barrier to progress in developing more effective, personalized treatments. Addiction theorists have identified a set of alcohol addiction research domain criteria (AARDoC) functional domains, believed to be important etiologic mechanisms for AUD. Yet, existing models meant to link these mechanisms to AUD-related behaviors and symptoms fail to consider etiology. Hence, many basic questions concerning the etiology of problematic drinking and AUD-related symptoms remain unresolved. The proposed work aims to identify the prospective contributions of functional domain neuro- behavioral indicators to the etiology of heavy drinking (HD) and AUD-related symptoms during adolescence and emerging adulthood, the decade of development when HD and AUD-related symptoms are most prevalent. We will enroll a target sample of 480 adolescents and emerging adults (160 in each of three partially overlapping age cohorts [50% female], pre-screened for elevated HD risk) to participate in a prospective study using an accelerated longitudinal design, which will allow us to characterize trajectories of alcohol involvement and AUD- related symptoms over a 10-year period of development within a five-year study. We will use a neuroclinical assessment approach to comprehensively characterize four functional domains—cognitive control/disinhibition (DIS), reward sensitivity (RS), anxiety (ANX), and incentive salience (IS)—using validated and reliable self- report, behavioral, and neurophysiological measures during each of three waves of data collection (15 months apart). Alcohol involvement, AUD-related symptoms, and social-environment factors will be assessed at 5-month intervals. Using this multi-wave, multimodal approach, we will address three specific aims: (1) characterize the influence of the functional domains on the etiology of alcohol involvement; (2) accounting for the influence of alcohol involvement, characterize the influence of the functional domains on the etiology of AUD-related symptoms; and (3) characterize the influence of HD on functional domain neurobehavioral indicators. Analyses will characterize how various combinations of domain indicators affect latent states of alcohol involvement (volume of consumption; patterns of use) and AUD-related symptoms (numbers of symptoms; clusters of symptoms) and transitions across latent states over time. This work will produce a unique and rich dataset, and its findings will directly inform the development of personalized intervention and treatment strategies that can be deployed to target the functioning of specific domains during periods when their influence is greatest.

PROJECT NARRATIVE The current project aims to better understand the psychological processes that lead to alcohol use and its consequences during adolescence and early adulthood. Our goal is to compare the relative importance of four key factors thought to promote addiction, and to understand how their influence changes over time. Findings from such work can lead to new, targeted addiction interventions.