Pituitary and Adrenocortical Responses to the Ovine Corticotropin Releasing Hormone in Depressed Patients and Healthy Volunteers

It has been suggested that limbic system-hypothalamic "overdrive" may be the underlying mechanism causing an augmented secretion of corticotropin releasing hormone (CRH), heightened adrenocortical responsiveness to corticotropin (adrenocorticotropic hormone) (ACTH), and alteration in cortisol feedback regulatory mechanisms as demonstrated by the dexamethasone suppression test. We examined pituitary and adrenocortical responses after morning administration of ovine CRH (oCRH) in 26 depressed patients and 11 healthy volunteers. Basal plasma ACTH concentrations were similar in both groups, whereas patients had a significantly diminished cumulative ACTH response after administration of oCRH. In contrast, basal total cortisol concentrations and cumulative cortisol responses to oCRH were similar in depressed patients and controls. Patients with melancholic features demonstrated the most profound ACTH blunting after oCRH, whereas patients separated according to dexamethasone suppression test results had similar ACTH and cortisol responses to oCRH. The present results extend data from prior studies utilizing oCRH in the evening and demonstrate a dysregulation of the functional integrity of the hypothalamic-pituitary-adrenocortical axis in depressive illness after a morning oCRH test at both central and peripheral hypothalamic-pituitary-adrenocortical axis sites.