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Effect of age on the cortisol response to human corticotropin-releasing hormone in depressed patients pretreated with dexamethasone

  • Ulrich von Bardeleben
    Affiliations
    From the Department of Psychiatry, University of Freiburg, Hauptstrasse 5, 7800 Freiburg, Germany

    Max-Planck-Institute for Psychiatry, Clinical Institute, Kraepelinstrasse 2-10, 8000 Munich 40, Germany
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  • Florian Holsboer
    Correspondence
    Address reprint requests to Florian Holsboer, M.D., Ph.D., Max-Planck-Institute for Psychiatry, Clinical Institute, Department of Psychiatry, Kraepelinstrasse 2-10, 8000 Munich 40, Germany
    Affiliations
    From the Department of Psychiatry, University of Freiburg, Hauptstrasse 5, 7800 Freiburg, Germany

    Max-Planck-Institute for Psychiatry, Clinical Institute, Kraepelinstrasse 2-10, 8000 Munich 40, Germany
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      A combined dexamethasone-human corticotropin-releasing hormone (hCRH) test was applied to 63 individuals—44 patients with major depressive episode (22 male, age 49.5 ± 13.4 years, and 22 female, 44.6 ± 11.9 years) and 19 normal male controls (age 42.0 ± 16.8 years). In normal controls, premedication with 1.5 mg dexamethasone at 11:00 pm substantially inhibited the stimulated release (expressed as area under the time course curve) of cortisol on the day after 100 μg hCRH was administered at 3:00 pm. In contrast, depressives responded with significant rises in cortisol (normal controls, 4.1 ± 4.0 × 103 ng/ml/min; depressives, 12.7 ± 8.3 × 103 ng/ml/min; p < 0.01). Multiple stepwise regression analysis disclosed significant effects of age (T = 3.55, p < 0.01) and severity of depression (T = 5.42, p < 0.01) on cortisol release in patients. Such an influence of age upon pituitary-adrenocortical regulation was absent among healthy controls. We postulate that the underlying mechanisms involve changes in corticosteroid receptors in the brain of depressives, impairing the sensitivity with which the brain-pituitary system can detect the dexamethasone feedback signal. Altered glucocorticoid neuroregulation in depression is apparently accelerated by the aging process.
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