OBJECTIVE: Neuroendocrine derangements have been reported in both depression and aggressive behavior. The purpose of this study was to evaluate whether the subset of depressed patients with anger attacks have a distinctive neuroendocrine abnormality. METHOD: The thyrotropin- releasing hormone (TRH) test was administered to 25 patients with major depression, 12 of whom reported having anger attacks, at the Depression Research Program of the Clinical Psychopharmacology Unit at the Massachusetts General Hospital. Twenty-two subjects underwent the TRH test again after 8 weeks of treatment with fluoxetine, a relatively selective serotonin uptake inhibitor. RESULTS: The depressed patients with anger attacks had a blunted prolactin response to TRH stimulation compared to the depressed patients without anger attacks. Treatment with fluoxetine was followed by an overall increase in the prolactin response to TRH among the depressed patients with anger attacks. The prolactin response to TRH also tended to predict the degree of response to treatment. CONCLUSIONS: These results suggest that the subset of depressed patients with anger attacks may have a greater central serotonergic dysregulation than depressed patients without such attacks.Abstract Teaser