PROJECT SUMMARY/ABSTRACT Broad/Long Term Objectives: The proposed research has two broad goals: to improve diagnostic conceptualization of AUD by adopting a symptom-focused approach that is more consistent with contemporary theoretical models of addiction (e.g., allostasis); and to ascertain the extent to which this approach can be translated into clinical applications. Specific Aims: The aims of the proposed project are to: characterize how individual AUD symptoms uniquely predict the onset, persistence, and recurrence (course) of other symptoms; resolve diagnostic heterogeneity and improve classification by examining symptom structure in a priori and empirically derived subgroups; and analyze the extent to which different symptoms and symptom subgroups predict clinical outcomes across different forms of treatment. Research Design and Method: The project will consist of secondary data analysis using both waves of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), the COMBINE study, and Project MATCH. In NESARC, symptom network modelling (SNM) will be used to identify key symptoms predicting the course of the other symptoms and identify core features of symptom subgroups. The project will also compare a priori subgroups based on etiologic (e.g., Conduct Disorder, heavy drinking patterns) risk factors and subgroups of symptom profiles empirically derived via cluster analysis. In MATCH and COMBINE, general mixed models and group factor analysis will be applied analyze the interaction between symptom profile, treatment condition, and treatment outcomes. Significance: This project will advance the understanding of how AUD diagnostic criteria reflect the endogenous processes proposed by modern addiction theories, help resolve diagnostic heterogeneity, and improve diagnostic validity. Additionally, the results of the project will allow for more effective tailoring and implementation of focused assessment and identification of potential targets for treatment. Training Plan and Environment: The training plan is designed to provide the applicant with quantitative, substantive, and practical training to facilitate a successful career as an independent investigator. The applicant will receive training in advanced multivariate statistics, application of theoretical models of addiction to clinical outcomes, open sciences practices, and general scientific writing. Training will take place at the University of Missouri’s Department of Psychological Sciences, which has an outstanding addiction training program funded by an NIAAA training grant (T32 AA013526; PI: Kenneth Sher). The mentoring team consists of experts in quantitative (Dr. Steinley, Dr. Wood) and substantive (Dr. Sher, Dr. Witkiewitz) research on AUD. Members of the team have a long collegial history, providing a synergistic training experience for the applicant.

PROJECT NARRATIVE The current diagnostic conceptualization of Alcohol Use Disorder (AUD) does not adequately reflect preclinical research and modern theoretical models of addiction, resulting in remarkable heterogeneity and unknown diagnostic validity. Rather than simply being manifestations of an underlying syndrome, symptoms may represent endogenous process that have been hypothesized to play etiological roles in addiction. The proposed project aims to model the course of relationships among symptoms, identify subgroups of symptom configurations, and characterize how symptom structure can inform clinical outcomes.