Dissociable hormonal, cognitive and mood responses to neuroendocrine challenge: evidence for receptor-specific serotonergic dysregulation in depressed mood.
Fifteen patients with major depression, dysthymia, or anxiety disorder with depressed mood (DSM-IV diagnoses) and 16 controls received single oral doses of 0.5mg/kg metachlorophenylpiperazine (m-CPP), a 5-HT(2C) agonist, and 10 mg ipsapirone, a 5-HT(1A) agonist, according to double-blind, placebo-controlled, cross-over design. The groups' levels of cortisol, adrenocorticotrophic hormone (ACTH) and prolactin did not differ at baseline. Both 5-HT agonists significantly elevated cortisol, ACTH, and prolactin. The cortisol response to ipsapirone was significantly blunted in major depression and dysthymia patients. Neuroendocrine responses to m-CPP did not differ between groups, but m-CPP selectively increased profile of mood states (POMS) depression and tenseness scores in patients. No effects of ipsapirone on mood were found. However, ipsapirone impaired memory performance in controls, but tended to improve memory performance in patients. The results support the evidence for both hypothalamic and possibly hippocampal 5-HT(1A) receptor desensitisation and non-hypothalamic, 5-HT(2C) receptor sensitisation, probably fronto-cortical, in patients with major depression and dysthymia.
Riedel
W J
WJ
Brain and Behaviour Institute, Department of Psychiatry and Neuropsychology, University Hospital, Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Wm.Riedel@Np.UniMaas.NL
Klaassen
T
T
Griez
E
E
Honig
A
A
Menheere
P P C A
PP
van Praag
H M
HM
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000339:Affect / Q000187:drug effects / Q000502:physiology*; D000375:Aging / Q000502:physiology; D000704:Analysis of Variance; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D018592:Cross-Over Studies; D003863:Depression / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D011388:Prolactin / Q000097:blood; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012727:Sex Characteristics
D006728:Hormones; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; C112812:serotonin 1C receptor; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D006854:Hydrocortisone