Am J Psychiatry 1989; 146:311-317
Copyright © 1989 by American Psychiatric Association
Pathophysiology of HPA axis abnormalities in patients with major depression: an update
RG Kathol, RS Jaeckle, JF Lopez and WH Meller
Department of Psychiatry, University of Iowa; Iowa City 52242.
Four hypotheses have been proposed to explain why nonsuppression on the
dexamethasone suppression test occurs in patients with major depression.
These include 1) increased metabolism of dexamethasone, 2) decreased
sensitivity of pituitary glucocorticoid receptors to dexamethasone, 3)
hyperresponsivity of the adrenal gland to ACTH stimulation, and 4)
increased central drive of the pituitary from hypothalamic/limbic
structures that overrides the action of the dexamethasone. A critical
review of the literature suggests that the last hypothesis is most closely
supported by the data. Despite this conclusion, factors other than
depression may be involved in hypothalamic-pituitary-adrenal axis
dysfunction.
