Persistent neuroendocrine dysregulation in major depressive disorder: a marker for early relapse.

Neuroendocrine challenge studies, including the dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) stimulation test, were administered to 86 patients meeting DSM-III criteria for major depressive disorder. Of 33 patients, 25 (76%) revealed normalization of abnormal DSTs at the time of symptomatic improvement, and 9 out of 26 patients (35%) revealed normalization of blunted TSH responses to TRH injection. Patients with normalized function revealed treatment responsiveness and low relapse rates (11%) similar to patients who had had normal neuroendocrine function at the time of admission. However, 11 of 23 patients with persistent dysregulation on either test (48%) relapsed within 6 months in contrast to 3 of 28 patients with normalized function (p less than 0.01) and 5 of 35 patients with normal neuroendocrine function on admission (p less than 0.02). These findings suggest that persistent dysregulation may be a valuable prognostic marker reflecting partial treatment responsiveness in some patients which predisposes them to early relapse. Both the DST and TRH tests appear to reflect neuroendocrine trait deficits which are independent of but interact with a coexisting predisposition to depressive disorder.