Adrenocortical responses and family history of alcoholism

Background: This study was designed to assess whether nonalcoholic offsprin g from families with a high density of alcohol-dependent individuals have a ltered hypothalamic-pituitary-adrenal (HPA) axis dynamics compared with non alcoholic subjects without a family history of alcohol dependence. Methods: Seventy-eight nonalcoholic subjects aged 18 to 25 were enrolled in the protocol. Thirty-nine subjects were offspring from families with a hig h density of alcohol dependence and were designated as family history-posit ive (FHP) subjects. Thirty-nine subjects were biological offspring of nonal cohol-dependent parents and were designated as family history-negative (FHN ) subjects. Subjects received naloxone hydrochloride (0 and 125 mu g/kg) an d cosyntropin (0, 0.25 mu g, and 250 mu g) in double-blind, randomized orde r and cortisol was monitored. A subset of subjects (11 FHP, 11 FHN) was adm itted to the General Clinical Research Center to measure serum cortisol lev els every 30 min for 24 hr. Results: FHP subjects had an increased cortisol response to opioid receptor blockade induced by naloxone. However, no group differences in cortisol we re uncovered during administration of cosyntropin or during monitoring of t he cortisol circadian profile. Conclusion: These observations suggest that differences in the cortisol dyn amics between FHP and FHN subjects are unmasked by opioid receptor blockade directed at the hypothalamus, but not when cortisol levels are directly pr ovoked at the level of the adrenal gland. In addition, unprovoked cortisol secretion monitored over a 24-hr interval cannot distinguish FHP from FHN s ubjects.