Corticotropin and cortisol response to human CRH as a probe for HPA system integrity in major depressive disorder

To explore the integrity of the hypothalamic-pituitary-adrenal (HPA) system in major depressive disorder, 12 patients and normal controls matched for sex, age, and body weight received 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) as an i.v. bolus dose. Compared to controls, depressed patients showed an elevation in baseline cortisol and a significant attenuation of net adrenocorticotropin (ACTH) responses, while cortisol secretion in response to hCRH was normal. These abnormalities in HPA axis function and apparent discordances in the interrelationships of ACTH and cortisol baseline and net stimulation responses between depressed patients and normal controls indicate, at least in part, a derangement of the glucocorticoid-dependent negative feedback circuitry and support the hypothesis that HPA hyperactivity in depression involves neurotransmitter-mediated hypothalamic hypersecretion of CRH.