Requested is a Scientist Development Award for Clinicians to study comorbid mood disorders in drug abuse and their implications for clinical treatment trials. Affective and anxiety syndromes are common among drug abusers. The majority of such syndromes probably result from drug toxicity or withdrawal, but a subgroup may represent true mood disorders, providing an opportunity for treatment with antidepressant medication. The problem is to accurately identify this subgroup. Training is proposed in structured diagnostic interview methodology, family-genetic methodology, clinical trials methodology and statistics, and psychopharmacology. It is hypothesized that treatable affective disorder is more likely to be chronologically primary, or to have persisted during periods of drug abstinence, or to be chronic. A version of the Structured Clinical Interview for DSM-III-R will be designed to isolate these historical dimensions. It is also hypothesized that treatable affective disorder will be associated with increased risk of affective disorder in biological relatives. Structured diagnosis and study of family pedigrees will be integrated into an ongoing trial of imipramine for cocaine and intravenous drug abusers in methadone treatment. Training in advanced experimental design and statistics will be undertaken. Psychopharmacology training will include study of the preclinical literature to target theoretically promising treatments. Pilot treatment trials will focus on cocaine and intravenous drug abuse. Studies initiated in later years will include a high risk study of offspring of drug abusers, exploration of the utility of biological markers, such as CO2 inhalation induced panic, to distinguish comorbid disorders, and formal clinical trials for promising treatment agents. The training and experience will foster a broad expertise in clinical trials in drug abuse, emphasizing the matching of treatment to patient based on diagnostic, familial, and biological predictors of response.
