Increased Levels in i Serum y-Aminobutyric Acid Young Men at High-Risk for (GABA) Alcoholism James C. Garbutt, Linda P. Miller, Gerald Kramer, Lori L. Davis, George A. Mason, Arthur J. Prange, Jr., and Frederick Petty Key Words: Alcoholism, GABA, family+ studies, biological markers Biol. PSYCHIA1"RY 1995:38:704--706 Introduction A relationship between alcoholism and the neurotransmitter y-aminobutyric acid (GABA) is likely, based on animal, in vitro. and human studies (Ueha and Kuriyama 1991, Little 1991, Hwang et al 1990, Tran et al 1981, Kril et al 1988, Freund and Ballinger 1988, Roy et al 1990). We have found plasma GABA to be low in several studies of recently detoxified alcoholics (Coffman and Petty 1985, Petty et al 1993). Moss et al (1990) studied the plasma GABA response to an alcohol challenge in sons of alcoholics and sons of nonalcoholics. In sons of alcoholics, but not sons of nonalcohol- ics, the alcohol challenge increased plasma GABA levels, whereas the placebo challenge did not. Also, sons of alcoholics had lower baseline plasma GABA levels than sons of nonalco- holics. We now report a study of serum GABA in young men at high risk for alcoholism and in a comparison group of young men at low risk for alcoholism. From the Clinical Research Unit, Dorothca {JCG, LPM. GAMh Dorothea Dlx Hospital, Raleigh, NC (JCG. LPM. AJPi: the Department of Psychiatry (JCG. GAM. AJPi, the Center tk~r Alcohol Studies and the Brain and Development Research Center (GAM. AJPI at the University of North Carolina at Chapel Hill, NC; the Department of Veterans Affairs Medical Center, Dallas, TX CGK. LLD, FP); and the Department of Psychiat U. University of Texas Southwestern Medical School, Dallas, TX (GK, LLD, FPJ. Address reprint requests to James C. Garbutt. MD. Clinical Re>earth Umt, Dorothea Dix Hospital. South Boylan A'~'enue, Raleigh. NC 2761)3 2176 Received May 10, 1995: accepted May 15. 1995 Methods Subject Recruitment Medically healthy Caucasian men at high risk (n = 8) or low risk (n - 12) for alcoholism were studied. Their respective mean _+ SD age, body surface area, and alcohol consumption were 23.6 _+ 2.7 years vs. 22.3 ± 1.5 years; 1.9 ± 0.13 m 2 vs. 1.9 ± 0.15 m 2, 29.5:2 24.6 drinks/30 days vs. 37.6 ± 17.l drinks/30 days, respectively. None of these differences was significant. Subjects were selected from a larger group of high-risk and low-risk subjects participating in a study of pituitary response to thyro- tropin-releasing hormone (Garbutt et al, in press). The method used to select subjects is described in detail in the publication of that study. Subjects were selected for the present study based on whether adequate serum had been saved at -70°C for assay of GABA. High-risk subjects were defined as family-history posi- tive (FHP) based on their having an alcoholic father according to Family History Research Diagnostic Criteria (Andreasen et al 1977). Low-risk subjects were defined as family-history negative IFHN) based on having no first- or second-degree relative with alcoholism Diagnostic and Behavioral Assessment A structured psychiatric interview was carried out using Re- search Diagnostic Criteria (Spitzer et al 1978). Subjects with evidence of a personal history of alcoholism, drug abuse or recent heavy drug use, or major depression or other significant © 1995 Societ? of Biological I~sychmtr_x 0006-3223195/$09.50 SSDI 0006-3223(95)00286-P