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.

We conclude that the HPA system is severely disturbed during alcohol withdrawal, possibly reflecting an exaggerated release of hypothalamic corticotropin and vasopressin.

We conclude that the HPA system is severely disturbed during alcohol withdrawal, possibly reflecting an exaggerated release of hypothalamic corticotropin and vasopressin.

Familial risk and environmental stress promote the development of alcohol dependence. We investigated whether a positive family history of alcoholism affects the neuroendocrine response to a standardized laboratory stress test in healthy subjects without alcohol use disorders. Twenty-four high-risk subjects with a paternal history of alcoholism (PHA) and 16 family history negative (FHN) controls were evaluated. Psychosocial stress was induced by having subjects deliver a 5-min speech and mental arithmetics in front of an audience on separate days, after drinking either placebo or ethanol (0.6 g/kg) in a randomized sequence. Adrenocorticotropin (ACTH) was measured in 10 plasma samples covering up to 75 min after the stress test. Plasma arginine vasopressin (AVP) was determined before the stressor, at the time of maximum ACTH secretion, and at 75 min after stress onset. The stress test induced a phasic increase in ACTH secretion. At the time of maximum ACTH, AVP was significantly increased in relation to baseline. Compared to placebo, alcohol administration significantly attenuated maximum ACTH concentration in PHA but not FHN subjects, and decreased AVP measured in the same samples in PHA but not FHN subjects. We conclude that activation of the hypothalamic-pituitary-adrenal system by psychosocial stress is accompanied by an increase in peripheral plasma AVP levels. Secretion of both ACTH and AVP suggest that alcohol attenuates the stress response selectively in PHA but not FHN subjects. This might imply some short-term positive alcohol effect in sons of alcoholics, but also constitute a mechanism by which their risk to develop alcohol use disorders is increased.

The acoustic startle reflex seems to be reduced in sons of alcoholics. The nonsignificant results during startle modification do not support the concept of increased reactivity to anxiety-related environmental stimuli as a mechanism promoting alcohol use disorders in subjects at increased family genetic risk for alcoholism.