Leo Sher, M.D.

Our research report, “Combined dexamethasone suppression-corticotrophin-releasing hormone stimulation test in medication-free major depression and healthy volunteers” was published 10 years ago in the December 2013 issue of the Journal of Affective Disorders (1).

A combined dexamethasone suppression– corticotrophin-releasing hormone stimulation (DEX–CRH) test has been developed as a potentially sensitive measure of hypothalamic–pituitary–adrenal (HPA) axis dysfunction in mood disorders. In this test, dexamethasone is administered orally at night to suppress cortisol, and then subjects receive an i.v. bolus of CRH in the afternoon of the following day. This approach measures HPA function downstream from CRH, including cortisol feedback or dexamethasone inhibition of adrenocorticotropic hormone (ACTH).

We compared cortisol and ACTH responses in individuals with major depression and healthy volunteers to the 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. This is important because abnormal cortisol reactivity measured using the DEX–CRH test has been reported in adults without psychopathology but having first-degree relatives with mood disorders. Demographics, DSM-IV diagnoses, and other clinical parameters were evaluated in patients with major depressive disorder (MDD) and healthy controls. Participants received an oral dose of 1.5 mg dexamethasone at 11 pm the day before CRH administration. On the following day, at 3 pm, 100 micrograms of ovine CRH were infused. Blood samples for determination of cortisol and ACTH were collected every 15 min from 3 pm to 4:15 pm. Cortisol and ACTH responses were calculated as areas under the curve.

We found no difference between cortisol baseline (i.e., post-dexamethasone) levels in patients and controls with or without controlling for age. We also observed no difference in cortisol responses in patients and controls, with or without controlling for age, and for both age and baseline cortisol levels. 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.

This study showed a dissociation of plasma ACTH and plasma cortisol in the DEX–CRH test in patients with MDD as compared to healthy controls. Our results suggest that the feedback inhibition of ACTH secretion by cortisol is compromised in MDD.

This study was supported by the American Foundation for Suicide Prevention grant to Dr. Leo Sher.

Reference

1. Sher L, Oquendo MA, Burke AK, Cooper TB, Mann JJ. Combined dexamethasone suppression-corticotrophin-releasing hormone stimulation test in medication-free major depression and healthy volunteers. J Affect Disord. 2013 Dec;151(3):1108-12. doi: 10.1016/j.jad.2013.06.049. Epub 2013 Jul 15.