Hormonal evidence for altered responsiveness to social stress in major depression

In patients with major depression, abnormalities in baseline cortisol secre tion and resistance to negative feedback are well established. However, it is unclear if patients with major depression have alterations in the hypoth alamic-pituitary-adrenal (HPA) response to stressors. While other challenge s to the HPA axis have used endocrine stimuli such as insulin-induced hypog lycemia, we now report of the response to a social stressor in patients wit h major depression and matched control subjects. We used the Trier Social S tress Test (TSST), a public speaking task followed by mental arithmetic cha llenge in front of a panel of judges. The results suggest that depressed pa tients manifest normal cortisol response to a social stressor, despite incr eased prestressor plasma cortisol. However, the P-endorphin response to the TSST was significantly smaller in the depressed patients compared to match ed controls. These data are similar to data found with exogenous corticotro pin-releasing-hormone challenge studies and suggest that elevated baseline cortisol can modulate the pituitary corticotroph response to a stressor, bu t that changes in adrenal sensitivity to ACTH result in a robust cortisol r esponse to this stressor. (C) 2000 American College of Neuropsychopharmacol ogy.