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This study investigates the relationships between cortisol escape from suppression by dexamethasone during a depressive episode, and the baseline activity of the hypothalamic-pituitary-adrenal (HPA) axis, circulating dexamethasone levels, and age. To this end, we measured urinary-free cortisol (UFC) excretion in 24-hr urine samples and the 8 am cortisol and dexamethasone levels after administration of 1 mg dexamethasone in 50 depressive patients. We found that up to 54% of the variance in the postdexamethasone cortisol values could be explained by the multiple regression on UFC, age, and dexamethasone levels. By utilizing these three parameters, the dexamethasone suppression test (DST) nonsuppressor/suppressor state was correctly identified in 92% of the subjects. It was shown that an important part of the variance in postdexamethasone cortisol is actually background variance, irrelevant to depression and produced by the cumulative effects of the three aforementioned parameters. Only a small part (<20%) of the variance in postdexamethasone cortisol is determined by the actual depressive state. It was concluded that (1) baseline hypersecretion of cortisol, (2) decrements in the bicavailability of the test substance, (3) increasing age, and (4) the depressive state per se—all of which are cumulative—contribute independently to cortisol escape from suppression by 1 mg dexamethasone.
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Received in revised form: December 14, 1989
Received: February 27, 1989
© 1990 Published by Elsevier Inc.