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-HT2C agonist, and 10 mg ipsapirone, a 5-HT1A agonist, according to double-blind, placebo-con trolled, cross-over design. The groups' levels of cortisol, adrenocorticotrophic hormone (ACTH) and prolactin did not differ at baseline. Both 5-HT agonists signficantly 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 peformance in patients. The results support the evidence for both hypothalamic and possibly hippocampal 5-HT1A receptor desensitisation and non-hypothalamic, 5-HT,c receptor sensitisation, probably fronto-cortical, in patients with major depression and dysthymia. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.