Better identification of subgroups of alcoholics with comorbid antisocial personality disorder (ASPD) has important implications for men and women seeking treatment. The proposed work requests 5 years funding to increase our understanding of the mechanisms that might possibly underlie elements of both ASPD and the risk for developing alcoholism. The research focuses on how serotonergic (5-HT) function, as measured by prolactin responses to a 5-HT releasing agent, fenfluramine, might be used as a biological marker to identify subgroups of alcoholics. the study will also explore the relationship between 5-HT function, platelet monoamine oxidase (MAO) activity levels, and psychometric measures of impulsivity. The hypotheses to be tested explore whether ASPD and alcoholism are separate disorders with some overlapping behaviors or if they are related to one another along a continuum. In addition, we predict that platelet MAO activity levels and the prolactin response to the fenfluramine challenge will be positively associated. Thus, both of these biological markers will be inversely correlated to measures of impulsive aggression. Ss will be a consecutive series of 18-55 year old ASPD and/or alcohol- dependent men and women admitted to inpatient services at 2 UCSD- affiliated hospitals. Our 4 groups will include: 30 ASP-alcoholics; 30 non-ASP alcoholics; 30 ASP non-alcoholics; and 30 NC. Structured interviews, standardized psychometric measures of impulsive aggression, resource person interviews, and all available public information will be obtained to establish careful diagnoses in these individuals. The study will use a double blind, randomized, fenfluramine (100 mg. p.o.) versus placebo control design. Ss will return to the hospital for the 2 separate challenge sessions within 7-14 days of discharge (a minimum of 5-7 weeks of total abstinence). Hormonal (prolactin, ACTH, cortisol) responses, heart rate, blood pressure, and body temperature changes over time will be determined at 30 min. intervals throughout the test sessions. Platelet MAO activity levels will also be obtained. This work should contribute significantly to our understanding of the mechanisms linking ASPD, alcohol dependence, nd impulsive aggressive personality traits, and should help better identify subgroups of alcoholics with different treatment needs.
