Effect of Ethanol on Hypothalamic–Pituitary–Adrenal System Response to Psychosocial Stress in Sons of Alcohol-Dependent Fathers

Abstract

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.

Hormonal Responses to Psychological Stress and Family History of Alcoholism

“…Our findings showing that cortisol responses were higher in Caucasian FHP subjects than in Caucasian FHN subjects are consistent with theories that greater reactivity to stress is associated with greater risks for alcoholism (Higley et al, 1991;Fahlke et al, 2000). To the best of our knowledge, only two studies have specifically examined the relationship of HPA axis hormonal responses to psychological stress with family history of alcoholism (Dai et al, 2002;Zimmermann et al, 2004). Our observations are in agreement with those of Zimmermann et al (2004), who demonstrated that FHP Caucasian males had higher cortisol and ACTH responses to the TSST compared to FHN Caucasian males.…”

“…Furthermore, differences in HPA-axis dynamics as a function of family history of alcoholism have been found by stimulating the HPA axis with the opioid receptor antagonist naloxone (Wand et al, 1998(Wand et al, , 1999a(Wand et al, , b, 2001Hernandez-Avila et al, 2002) and CRH . More recently, hormonal responses to activation of the HPA axis by psychological stressors have been reported to differ in subjects at high and low risk of alcoholism (Dai et al, 2002;Zimmermann et al, 2004). However, results have been contradictory and the nature of these associations remains inconclusive.…”

Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice

“…Several reports have shown that, when exposed to stressful events, humans are more likely to relapse to ethanol and other drugs (Chaplin et al 2010;Fox et al 2005;Kosten et al 1986;Sinha et al 2000). A factor long known to increase the risk for development and maintenance of alcohol use disorders is environmental stress (Zimmermann et al 2004). Environmental stress may produce an exaggerated endocrine response, which is normalized by alcohol, often in conjunction with genetic risk factors for alcoholism (Sinha 2001(Sinha , 2007.…”

“…Stress produces a cascade of physiological and psychological effects, each with a distinctive time course. In turn, alcohol administration also influences both ACTH and cortisol secretion (Zimmermann et al 2004). Thus, there are bi-directional relationships between alcohol and stress: alcohol influences responses to stress, and stress changes reactions to alcohol, depending on an individual's pattern of response to alcohol (Childs et al 2011).…”

“…Thus, there are bi-directional relationships between alcohol and stress: alcohol influences responses to stress, and stress changes reactions to alcohol, depending on an individual's pattern of response to alcohol (Childs et al 2011). Alcohol's anxiolytic effect is probably another important underlying mechanism of abuse that may induce reinforcement of abuse habits by reduction of negative feelings and negative self-perception, most probably leading to a repetition effect resulting in habituation, although the dampening of stress hormone response by alcohol does not appear to be paralleled by any effect on how subjects perceived the stress situation (Zimmermann et al 2004).…”