An initial study of the relationship between platelet adenylyl cyclase activity and alcohol use disorder criteria.

Low platelet adenylyl cyclase (AC) activity has been previously proposed to be a trait marker reflecting a genetic predisposition to alcohol dependence. To determine whether low platelet AC activity in alcohol-dependent subjects may be related to specific diagnostic criteria of DSM-IV and ICD-10 alcohol use disorders, we analyzed responses obtained in structured clinical interviews of 36 subjects who were determined to be alcohol-dependent Platelet AC activity when stimulated by guanylyl-imidodiphosphate [Gpp(NH)p] or forskolin was significantly lower in alcohol-dependent subjects as a group, compared with controls. When we analyzed the responses of the alcohol-dependent subjects to questions used to establish the diagnosis of alcohol abuse/dependence and dichotomized the subjects by positive or negative responses, we found that Gpp(NH)p- and forskolin-stimulated platelet AC activities were significantly lower among those alcohol-dependent subjects who had positive responses to questions related to drinking despite negative effects on mood ("Did you ever continue to drink even though you knew it was making you feel depressed, uninterested in things, or suspicious or distrustful of other people?"), drinking despite negative effects on health ("Did you ever continue to drink even though you knew it was causing you a health problem or making a health problem worse?"), or violence when drinking ("Did you get into physical fights while drinking or right after drinking?"). The alcohol-dependent subjects who had negative responses to these questions exhibited Gpp(NH)p- and forskolin-stimulated platelet AC activity that did not differ significantly from values in control subjects. The DSM-IV diagnosis of antisocial personality disorder did not distinguish alcohol-dependent subjects with regard to platelet AC activity. Gpp(NH)p and forskolin-stimulated AC activity may distinguish certain subtypes of alcoholics (i.e., those who develop negative mood in response to drinking, those who continue drinking despite health effects, and those who become violent while drinking).