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Corticotropin-Releasing Hormone and HPA Axis Pathophysiology

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The DST, a test originally designed to aid in the diagnosis of Cushing's syndrome, was one of the first endocrine challenge tests to be studied in psychiatric patients. Studies of patients with mood disorders using the DST provided some of the first evidence of abnormal HPA axis function in depression (Table 45–1). The DST consists of the administration of a low dose (1 mg) of the synthetic glucocorticoid dexamethasone at 2300 h followed by measurement of plasma cortisol concentrations at two or three time points the following day. Dexamethasone acts at the level of the anterior pituitary corticotrophs to reduce the secretion of ACTH, resulting in a decrease in the synthesis and release of cortisol from the adrenal cortex. Failure to suppress plasma cortisol concentrations after dexamethasone administration suggests impaired feedback regulation and hyperactivity of the HPA axis.

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Table Reference Number
TABLE 45–1. Alterations in hypothalamic-pituitary-adrenal (HPA) axis activity in unipolar depression
Table Reference Number
TABLE 45–2. Alterations in hypothalamic-pituitary-adrenal (HPA) axis activity in bipolar disorder

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