Hypothalamic-pituitary-adrenal system adaptation to detoxification in alcohol-dependent patients is affected by family history of alcoholism

Background Alcohol withdrawal profoundly affects the hypothalamic-pituitary-adrenocortical (HPA) system. We investigated whether a family history of alcoholism modulates HPA response to pharmacologic intervention during detoxification in alcohol-dependent patients. Methods Sixteen family history negative (FH-N) and 19 family history positive (FH-P) alcohol-dependent patients were admitted for withdrawal. All 35 patients were investigated 1 week after remission of withdrawal symptoms; 17 patients were also tested during acute withdrawal. Dexamethasone 1.5 mg was given orally at 11 pm, followed by 100 μg corticotropin-releasing hormone (hCRH) administered intravenously at 3 pm the following day. Plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations were determined at 0, 30, 45, 60, and 75 min after CRH. Results During withdrawal, cortisol but not ACTH secretion was increased in patients compared with 19 control subjects matched for age and gender. After withdrawal, cortisol was normal in FH-P but still increased in FH-N patients versus control subjects, and ACTH was marginally decreased in FH-P patients only. Both hormones were increased in FH-N versus FH-P patients. Conclusions Recovery from alcohol withdrawal-induced impairment of HPA system regulation occurs earlier in FH-P than FH-N patients, indicating that the efficacy of central neuroadaptation to this ethanol-related stimulus may be related to genetic factors.