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 serotonergic (5-HT) activity. However, in depression the relationship between altered cortisol levels and brain 5-HT function remains to be clarified. The aim of this study was to investigate whether hypothalamic-pituitary-adrenal (HPA) axis hyperactivity is associated with 5-HT dysfunction in depressed patients, especially in those with suicidal behaviour. Cortisol levels following the dexamethasone suppression test (DST, 1 mg PO) and prolactin, corticotropin 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-free DSM-IV major depressed inpatients (40 with a history of suicide attempt, 31 without) and 34 hospitalized healthy control subjects. Depressed patients showed higher post-DST cortisol levels but similar responses to d-FEN compared with control subjects. Hormonal responses to d-FEN were not correlated with cortisol levels (basal or post-DST). Among the depressed patients, DST 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 hormonal responses to d-FEN but comparable basal and post-DST cortisol levels. Taken together these results suggest that, in depression, HPA axis hyperactivity is not responsible for the reduced 5-HT activity found in patients with a history of suicidal behavior.
Duval
F
F
Centre Hospitalier, 27 rue du 4ème Spahis Marocain, 68250, Rouffach, France
Mokrani
M C
MC
Correa
H
H
Bailey
P
P
Valdebenito
M
M
Monreal
J
J
Crocq
M A
MA
Macher
J P
JP
D000311:Adrenal Glands / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003863:Depression / Q000503:physiopathology*; D003907:Dexamethasone; D005260:Female; D005277:Fenfluramine; D005938:Glucocorticoids; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D011388:Prolactin / Q000097:blood; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors; D013406:Suicide, Attempted
D000324:Adrenocorticotropic Hormone; D003907:Dexamethasone; D005277:Fenfluramine; D005938:Glucocorticoids; D006854:Hydrocortisone; D011388:Prolactin; D012701:Serotonin; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors