Effect of age on the cortisol response to human corticotropin-releasing hormone in depressed patients pretreated with dexamethasone.

A combined dexamethasone-human corticotropin-releasing hormone (hCRH) test was applied to 63 individuals--44 patients with major depressive episode (22 male, age 49.5 +/- 13.4 years, and 22 female, 44.6 +/- 11.9 years) and 19 normal male controls (age 42.0 +/- 16.8 years). In normal controls, premedication with 1.5 mg dexamethasone at 11:00 PM substantially inhibited the stimulated release (expressed as area under the time course curve) of cortisol on the day after 100 micrograms hCRH was administered at 3:00 PM. In contrast, depressives responded with significant rises in cortisol (normal controls, 4.1 +/- 4.0 x 10(3) ng/ml/min; depressives, 12.7 +/- 8.3 x 10(3) ng/ml/min; p less than 0.01). Multiple stepwise regression analysis disclosed significant effects of age (T = 3.55, p less than 0.01) and severity of depression (T = 5.42, p less than 0.01) on cortisol release in patients. Such an influence of age upon pituitary-adrenocortical regulation was absent among healthy controls. We postulate that the underlying mechanisms involve changes in corticosteroid receptors in the brain of depressives, impairing the sensitivity with which the brain-pituitary system can detect the dexamethasone feedback signal. Altered glucocorticoid neuroregulation in depression is apparently accelerated by the aging process.