Cortisol response to a combined dexamethasone-human corticotrophin-releasing hormone challenge in patients with depression

Abstract

Abstract We administered a combined dexamethasone-human corticotrophin-releasing hormone (hCRH) challenge test to 14 in-patients with a major depressive episode and to 14 age-matched controls. After pretreatment with 1.5 mg dexamethasone at 2300 h the day before, 100 mug hCRH was administered iv at 1500 h. Blood samples for cortisol determinations by radioimmunoassay were drawn at 1400 h, 1430 h and 1500 h before infusion of hCRH and thereafter every 15 min until 1700 h. Cortisol secretion after injection of hCRH assessed as area under the curve was significantly increased in patients with depression when compared to controls (14.5 +/- 4.3 ng x min x 1,000/ml vs 3.1 +/- 2.4 ng x min x 1,000/ml). Multiple regression analysis among patients revealed a significant impact of age and severity of depression upon hCRH-induced cortisol secretion, whereas in normal controls no significant influence of age on cortisol secretion after hCRH emerged. Our data show that in depressed patients hCRH evokes an escape from dexamethasone-induced suppression of the pituitary-adrenocortical activity, whereas it fails to do so among controls. This finding suggests that at the pituitary level the action of hCRH is enhanced by a factor that is less sensitive to dexamethasone suppression in depression. We postulate that this factor is vasopressin.