Objective: The stress response is a process whereby the body adapts to disruptions in homeostasis, in part through the secretion of specific hormones and neurotransmitters. A healthy stress response is promptly activated at the first signs of homeostatic disruption but quickly terminates after cessation of the stressful experience. Both blunted and overactive hormone responses to stress are maladaptive and are associated with a variety of neuropsychiatric and metabolic abnormalities. Previous studies of abstinent alcohol-dependent individuals have shown that compared with healthy control subjects, the alcoholics have blunted ACTH and/or cortisol responses to activation of the hypothalamic-pituitary-adrenal (HPA) axis when interrogated pharmacologically or psychologically. Although far fewer in number, studies using psychological stress have shown an attenuated cortisol response in alcohol-dependent individuals compared with social drinkers. Moreover, HPA axis response in alcohol-dependent subjects is likely inşuenced by other psychological factors, including current mood states and comorbid psychological disorders. Individuals with anxiety and/or depression but without alcohol dependence have also been described to have altered hormone responses to experimentally induced stressors. Accordingly, the aim to this study was to determine stress hormone responses to a psychological stressor in abstinent alcohol-dependent subjects without comorbidities who were matched to first-degree relatives and to healthy control subjects, to explore if it is possible that cortisol stress hypo-responsiveness might be an important characteristic of persons prone to alcohol dependence.
Method: Subjects were 32 hospitalized male patients, aged between 20 to 60 years, who included alcoholics and 32 first degree relatives and 30 community controls. All patients met the previously listed general inclusion criteria plus criteria for alcohol dependence by DSM-IV and had abstinence period>3 weeks. Controls and first-degree relatives had no reported history of DSM-IV Axis I disorders including any substance use disorder. Subjects reported to the general clinical research center study room at 9:00 to undergo a psychological stress test. The test consisted 30 minutes of public speaking followed by 15 minutes of mental arithmetic. Two baseline (-30 min, immediately before the beginning the test) and five post-stress test (15, 30, 45, 60, 90 minutes) blood samples were drawn.
Results: In agreement with these previous reports, we found a deficient activation of the HPA axis by psychological stress, with a not significant exercise-induced ACTH/cortisol rise after 3 weeks of abstinence in alcoholics in comparison with first degree relatives and controls. We found a deficient activation of the HPA axis, with a significant exercise-induced ACTH rise (not cortisol rise) (at the following time points: 15, 30, 60, 90 minutes) in the first degree relatives in comparison with the controls.
Conclusion: This difference suggest that the HPA hypo responsiveness might be an important characteristic of individuals prone to alcohol dependence and this difference might suggest the disruption in first degree relatives that occurs at the pituitary level.