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Free keywords:
alcoholism; alcohol withdrawal; HPA system; family history; CRH; genetic factors
Abstract:
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 mug 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. (C) 2003 Society of Biological Psychiatr
