CORTICOSTEROID RECEPTOR FUNCTION IS DECREASED IN DEPRESSED-PATIENTS

Decreased feedback control of the hypothalamic-pituitary-adrenocortica l (HPA) system as revealed by the combined dexamethasone and corticotr opin-releasing hormone (DEX-CRH) test has been documented in the vast majority of patients with affective disorders. This finding was interp reted as a failure at the level of the glucocorticoid receptor (GR)-me diated feedback action, which apparently fails to restrain HPA activit y in the presence of elevated plasma corticosteroid levels. To test th is hypothesis we conducted the DEX/CRH test using increasing doses of DEX in order to establish a dose-response relationship. We used three different DEX doses(0.75, 1.5, 3.0 mg) in three groups of depressed pa tients and controls. As expected, increasing DEX doses were associated with decreasing amounts of adrenocorticotropin (ACTH) and cortisol be ing released after CRH injection. However, dose-response curves for bo th plasma ACTH and cortisol concentrations were shifted to higher area under the curve (AUG) values among patients compared to controls. Pre treatment with 0.75 and 1.5 mg DEX produced significantly higher AUC v alues for both plasma ACTH and cortisol values among patients. These d ifferences became less obvious with the higher DEX doses, indicating t hat the dose of 1.5 mg used in the majority of clinical studies so far is well suited to differentiate between healthy controls and patients . The reported data here are consistent with the hypothesis that an al tered GR capacity or function underlies the exaggerated HPA activity i n depression.