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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AA009735-03
Application #
2045992
Study Section
Clinical and Treatment Subcommittee (ALCP)
Project Start
1993-07-01
Project End
1998-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Anthenelli, R M; Maxwell, R A; Geracioti Jr, T D et al. (2001) Stress hormone dysregulation at rest and after serotonergic stimulation among alcohol-dependent men with extended abstinence and controls. Alcohol Clin Exp Res 25:692-703
Berlin, I; Anthenelli, R M (2001) Monoamine oxidases and tobacco smoking. Int J Neuropsychopharmacol 4:33-42
Murray, M G; Anthenelli, R M; Maxwell, R A (2000) Use of health services by men with and without antisocial personality disorder who are alcohol dependent. Psychiatr Serv 51:380-2
Anthenelli, R M; Maxwell, R A (2000) Cigarette smoking decreases the prolactin response to serotonergic stimulation in subgroups of alcoholics and controls. Alcohol Clin Exp Res 24:987-95
Anthenelli, R M; Smith, T L; Craig, C E et al. (1995) Platelet monoamine oxidase activity levels in subgroups of alcoholics: diagnostic, temporal, and clinical correlates. Biol Psychiatry 38:361-8
Anthenelli, R M; Smith, T L; Irwin, M R et al. (1994) A comparative study of criteria for subgrouping alcoholics: the primary/secondary diagnostic scheme versus variations of the type 1/type 2 criteria. Am J Psychiatry 151:1468-74