Lack of effect of HPA axis hyperactivity on hormonal responses to d-fenfluramine in major depressed patients: implications for pathogenesis of suicidal behaviour

There is evidence for inhibitory effects of adrenocorticosteroids on seroto nergic (5-HT) activity. However, in depression the relationship between alt ered cortisol levels and brain 5-HT function remains to be clarified. The a im of this study was to investigate whether hypothalamic-pituitary-adrenal (HPA) axis hyperactivity is associated with 5-HT dysfunction in depressed p atients, especially in those with suicidal behaviour. Cortisol levels follo wing the dexamethasone suppression test (DST, 1 mg PO) and prolactin, corti cotropin and cortisol responses to the d-fenfluramine test (d-FEN, 45 mg PO )- a specific 5-HT releaser/uptake inhibitor - were measured in 71 drug-fre e DSM-IV major depressed inpatients (40 with a history of suicide attempt, 31 without) and 34 hospitalized healthy control sujects. Depressed patients showed higher post-DST cortisol levels but similar responses to d-FEN comp ared with control subjects. Hormonal responses to d-FEN were not correlated with cortisol levels (basal or post-DST). Among the depressed patients, DS T suppressors and DST nonsuppressors exhibited no significant difference in endocrine responses to d-FEN. However, patients with a history of suicide attempt, when compared with patients without such a history, showed lower h ormonal responses to d-FEN but comparable basal and post-DST cortisol level s. Taken together these results suggest that, in depression, HPA axis hyper activity is not responsible for the reduced 5-HT activity found in patients with a history of suicidal behavior. (C) 2001 Elsevier Science Ltd. All ri ghts reserved.