Sher L, Oquendo MA, Burke AK, Cooper TB, Mann JJ.
J Affect Disord. 2013 Jul 15. pii: S0165-0327(13)00529-6. doi: 10.1016/j.jad.2013.06.049. [Epub ahead of print]

Abstract
BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis is dysfunctional in a subgroup of mood disorders. METHODS: We compared cortisol and adrenocorticotropic hormone (ACTH) responses in major depression and healthy volunteers to the combined dexamethasone suppression-corticotrophin-releasing hormone stimulation (DEX-CRH) test. Unlike other published studies, the study patients were medication-free and the healthy volunteers did not have first-degree relatives with a mood or psychotic disorder.Demographics, DSM-IV diagnoses and other clinical parameters were evaluated in major depressive disorder (MDD) and healthy control groups. Participants received an oral dose of 1.5mg dexamethasone at 11pm the day before CRH administration. On the following day, at 3pm, 100µg of ovine CRH was infused. Blood samples for determination of cortisol and ACTH were collected every 15min from 3pm to 4:15pm. Cortisol and ACTH responses were calculated as areas under the curve. RESULTS: Controlling for age, baseline (i.e., post-dexamethasone) ACTH levels were higher in depressed patients compared to controls (p=0.01). There was a trend for higher ACTH responses in depressed patients compared to the control group (p=0.08). In depressed patients, cortisol and ACTH responses correlated positively with age, duration of illness and number of hospitalizations. LIMITATIONS: Because of the cross-sectional study design we can only evaluate the nature of potential HPA axis disturbances that were present in patients when they are acutely depressed. CONCLUSIONS: Feedback inhibition of ACTH secretion by cortisol is compromised in MDD, and this is independent of an age effect on the HPA axis function.