PROJECT SUMMARY/ABSTRACT This K01 proposal integrates research and training to address gaps in our understanding of the associations between substance use disorders (SUDs) and other forms of psychopathology. Extant research has consistently demonstrated that SUDs share phenotypic and etiologic variance with other forms of psychopathology, such as externalizing and internalizing. Despite this, most research into the classification and etiology of SUDs treats them as isolated from each other and other forms of psychopathology. A clearer understanding of the ways in which SUDs covary, both phenotypically and genetically, is essential to increase specificity of SUD phenotypes, which can be used as targets in future research, and which can improve classification and treatment in clinical settings. The overall goal of this award is to facilitate Dr. Poore’s development as an independent scientist working at the intersection of psychiatric nosology, statistical genetics, and translational science to uniquely equip her to address these research questions. The proposed training integrates Dr. Poore’s background in clinical psychology and classification of psychopathology with training in substance use, advanced statistical genetics methods, and translational research skills. The following training objectives will be completed during the award period to accomplish these goals: 1) training in the interface between SUDs and internalizing psychopathology; 2) training in biological annotation of genetic variants and multi-ancestry statistical genetic methods; 3) integrating basic and clinical research; and 4) gaining professional competencies essential for independence.The research aims proposed in this K01 use multiple analytic approaches to understand the relationships between substance use disorders and other forms of psychopathology and the extent to which better classification can improve prediction of treatment response in a treatment seeking population. These analyses will rely on several sources of data, including large, deeply phenotyped samples that include broad measures of psychopathology and relevant outcomes, previously published genome-wide association studies of psychiatric disorders, and data collected from individuals seeking treatment at the Rutgers University Behavioral Health Center to accomplish the following aims: 1) Use advanced quantitative methods to model the phenotypic overlap between SUDs and other forms of psychopathology; 2) Identify and characterize genetic variants that influence SUDs and other forms of psychopathology; 3) Quantify the clinical utility of phenotypic and genetic psychopathology clusters.

PROJECT NARRATIVE The interface between substance use, externalizing, and internalizing disorders is complex and poorly characterized, which limits efforts to identify causes, correlates, and treatments for substance use disorders (SUDs). The training and research described in this proposal will integrate phenotypic classification of SUDs with statistical genetics and translational science to better characterize the phenotypic and genetic relationships among SUDs and other forms of psychopathology. This project has the potential to improve the specificity of phenotypes used in future studies, aid in gene discovery of SUDs, and improve the clinical utility of classification and gene-identification efforts for SUDs.