Neuroendocrine aspects of hypercortisolism in major depression.
A consistent finding in biological psychiatry is that hypothalamic-pituitary-adrenal (HPA) axis physiology is altered in humans with major depression. These findings include hypersecretion of cortisol at baseline and on the dexamethasone suppression test. In this review, we present a process-oriented model for HPA axis regulation in major depression. Specifically, we suggest that acute depressions are characterized by hypersecretion of hypothalamic corticotropin-releasing factor, pituitary adrenocorticotropic hormone (ACTH), and adrenal cortisol. In chronic depressions, however, enhanced adrenal responsiveness to ACTH and glucocorticoid negative feedback work in complementary fashion so that cortisol levels remain elevated while ACTH levels are reduced. In considering the evidence for hypercortisolism in humans, studies of nonhuman primates are presented and their utility and limitations as comparative models of human depression are discussed.
Parker
Karen J
KJ
Department of Psychiatry and Behavioral Sciences, Stanford University Medical School, 1201 Welch Road, MSLS Room P104, Mail Code 5485, Stanford, CA 94305-5485, USA. kjparker@stanford.edu
Schatzberg
Alan F
AF
Lyons
David M
DM
D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D003865:Major Depressive Disorder / Q000503:physiopathology*; D006801:Humans; D006854:Hydrocortisone / Q000502:physiology; D009490:Neurosecretory Systems / Q000503:physiopathology*
D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone