PATHOPHYSIOLOGY OF CORTICOSTEROID DYSREGULATION IN DEPRESSION

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The overall objective of this proposal is to evaluate the role of Type I glucocorticoid receptors (MR) in the hippocampus and septum in the regulation of the HPA axis studies which have utilized the synthetic glucocorticoid, dexamethasone. The research proposed has 4 objectives: 1) Confirm that a single dose of corticosterone which suppresses HPA axis secretion is operating through mineralcorticoid receptors (MR) and evaluate the plasma pharmacokinetics of corticosterone. 2) Examine the effects of an MR antagonist (spironolactone) on ACTH and cortisol secretion and the zenith and nadir of the circadian rhythm of the HPA axis. 3) Compare the HPA axis responses to corticosterone and the plasma pharmacokinetics in depressed patients and controls, and 4) examine the relationship between the DST result and the response to corticosterone, and specific patient and illness characteristics [age, sex, family history of mood disorder, cumulative history of depression, severity of depression, and duration of episode].