Platelet adenylyl cyclase activity as a trait marker of alcohol dependence

Background: There is compelling evidence that genetic factors play a major role in the development of alcohol dependence. Platelet adenylyl cyclase (A C) activity has been proposed as a biochemical marker for differentiating a lcohol-dependent and nondependent subjects, but the sensitivity and specifi city of this marker have not been ascertained. The objective of this study was to determine the sensitivity and specificity of platelet AC activity in identifying alcohol-dependent subjects and to ascertain the effect of medi cal/psychiatric variables, drinking and smoking history, and age and body w eight on AC activity. Methods: The cross-sectional study was conducted from 1995 to 1998. Partici pants were 210 Australian White men who were community volunteers and alcoh ol treatment inpatients in Sydney, Australia. There were 41 nondrinkers, 14 0 drinkers, and 29 men who were entering alcohol treatment. The main outcom e measure was platelet AC activity. Classification variables were plasma et hanol, gamma-glutamyltransferase, aspartate aminotransferase, serum carbohy drate-deficient transferrin (CDT), and urinary 5-hydroxytryptophol-hydroxyi ndoleacetic acid (5-HTOL/5-HIAA) levels, and World Health Organization/Inte rnational Society for Biomedical Research on Alcoholism Interview Schedule variables, which included alcohol use and dependence criteria. Results: Among subjects who reported abstinence for at least 4 days, both c esium fluoride (CsF)- and forskolin-stimulated platelet AC activities were significantly lower in those with a lifetime history of alcohol dependence compared with those with no such history (p < 0.005 and p < 0.05, respectiv ely). The sensitivity and specificity of CsF-stimulated AC activity to disc riminate individuals with a lifetime history of alcohol dependence were 75% and 79%, respectively. Similar values for sensitivity and specificity for CsF-stimulated AC activity were calculated when discriminating current alco hol dependence in the subjects in our sample. Irrespective of the history o f alcohol dependence, persons who had consumed alcohol recently (within the last 3-4 days) showed significantly higher mean basal, CsF-stimulated, and forskolin-stimulated AC activity (p < 0.001), as did those who had elevate d 5-HTOL/5-HIAA ratios or CDT levels, indicative of recent (heavy) drinking The "normalization" of platelet AC activity to baseline levels after an in dividual stops drinking may be related to the generation of new platelets d uring the abstinence period. Conduct disorder and antisocial personality di sorder were not associated with low AC activity, but low forskolin-stimulat ed AC activity was associated with major depression. Conclusions: We found that CsF- and forskolin-stimulated platelet AC activi ty discriminates between subjects with and without alcohol dependence in a population of subjects who had not consumed significant quantities of ethan ol recently. Recent alcohol consumption is a confounding variable that can alter the measured levels of AC activity. Forskolin-stimulated platelet AC activity also may be influenced by a history of major depression.