Adrenocorticotropic hormone, β-endorphin and cortisol responses to oCRH in Unipolar Depressed Patients Pretreated with Dexamethasone

1. 1. Corticotropin-releasing hormone (ovine CRH, 100 μg intravenous bolus) was given to 63 unipolar depressed inpatients following the 1 mg overnight dexamethasone suppression test (DST). The depressed patients included 18 minor, 24 simple major and 21 melancholic subtypes. 2. 2. Baseline or postdexamethasone plasma levels of intact adrenocorticotropic hormone (ACTH), β-endorphin/β-lipotropin (βEND/βLPH), Cortisol, and dexamethasone were measured, as well as the post DST + CRH hormone responses. 3. 3. CRH administration 9.5 hr after dexamethasone resulted in a significant enhancement of ACTH, ßEND/ßLPH and cortisol secretion. The post DST+CRH ACTH and ßEND/ ßLPH-but not cortisol - values exceeded their baseline hormone levels. The post DST+CRH ACTH - but not ßEND/ßLPH or cortisol - levels were significantly higher in major depressives compared to minor depressives. The post DST+CRH ACTH and ßEND/ ßLPH - but not cortisol - levels were significantly higher in DST nonsuppressors than suppressors. The post DST+CRH ACTH levels were significantly and positively related to severity of illness. 4. 4. The results provide evidence that the pathophysiology underlying the abnormal DST+CRH and DST tests in melancholia is localized at the pituitary level and may consist of a CRH-driven breakthrough of corticotropic cell secretion synergized by central and peripheral agents, in conjunction with a decrease in glucocorticoid feedback suppressibility.