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 propos ed 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 D SM-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 guany lyl-imidodiphosphate [Gpp(NH)p] or forskolin was significantly lower i n alcohol-dependent subjects as a group, compared with controls. When we analyzed the responses of the alcohol-dependent subjects to questio ns used to establish the diagnosis of alcohol abuse/dependence and dic hotomized the subjects by positive or negative responses, we found tha t Gpp(NH)p-and forskolin-stimulated platelet AC activities were signif icantly 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 ma king you feel depressed, uninterested in things, or suspicious or dist rustful of other people?''), drinking despite negative effects on heal th (''Did you ever continue to drink even though you knew it was causi ng you a health problem or making a health problem worse?''), or viole nce when drinking (''Did you get into physical fights while drinking o r right after drinking?''). The alcohol-dependent subjects who had neg ative responses to these questions exhibited Gpp(NH)p-and forskolin-st imulated platelet AC activity that did not differ significantly from v alues in control subjects. The DSM-IV diagnosis of antisocial personal ity disorder did not distinguish alcohol-dependent subjects with regar d to platelet AC activity. Gpp(NH)p and forskolin-stimulated AC activi ty may distinguish certain subtypes of alcoholics (i.e., those who dev elop negative mood in response to drinking, those who continue drinkin g despite health effects, and those who become violent while drinking) .