Effect of ethanol on hypothalamic-pituitary-adrenal system response to psychosocial stress in sons of alcohol-dependent fathers.

Familial risk and environmental stress promote the development of alcohol dependence. This study tested two hypotheses: that a family history for alcoholism is associated with (i) a greater stress response and (ii) more effective stress response dampening by alcohol. We studied 29 high-risk subjects with a paternal history of alcoholism (PHA) and 23 family history negative (FHN) controls all aged 18-26 years, who were recruited using a representative sample of the local area population. Psychosocial stress was induced by having subjects deliver a speech and perform mental arithmetics in front of an audience on two separate days, after drinking either placebo or alcohol (0.6 g/kg) in a randomized double-blind crossover design. Plasma cortisol and adrenocorticotropin (ACTH) were measured up to 90 min after the test. The stress task induced a phasic increase of both hormones in PHA and FHN subjects during all experimental conditions except in tests where FHN subjects received alcohol during the second day. ACTH secretion was higher in PHA subjects during placebo experiments, but equal to controls after alcohol administration. The alcohol-induced attenuation of ACTH response was statistically significant in PHA, but not FHN, subjects. Cortisol response was higher in PHA than FHN probands if placebo was administered during the first test, but equal if subjects received alcohol first. The increased stress response and its stronger dampening by alcohol in sons of alcoholic fathers suggest a mechanism by which predisposition to develop alcohol use disorders might be expressed, implying that a transient favorable alcohol effect might occur in PHA, but not FHN, subjects.