ADRENOCORTICOTROPIC HORMONE, BETA-ENDORPHIN AND CORTISOL RESPONSES TOOCRH IN UNIPOLAR DEPRESSED-PATIENTS PRETREATED WITH DEXAMETHASONE

1. Corticotropin-releasing hormone (ovine CRH, 100 mu g intravenous bo lus) 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. Ba seline or postdexamethasone plasma levels of intact adrenocorticotropi c hormone (ACTH), beta-endorphin/beta-lipotropin (beta END/beta LPH), cortisol, and dexamethasone were measured, as well as the post DST+CRH hormone responses.3. CRH administration 9.5 hr after dexamethasone re sulted in a significant enhancement of ACTH, beta END/beta LPH and cor tisol secretion. The post DST+CRH ACTH and beta END/beta LPH but not c ortisol - values exceeded their baseline hormone levels. The post DSTCRH ACTH - but not beta END/beta LPH or cortisol - levels were signifi cantly higher in major depressives compared to minor depressives. The post DST+CRH ACTH and beta END/beta LPH - but not cortisol - levels we re significantly higher in DST nonsuppressors than suppressors. The po st DST+CRH ACTH levels were significantly and positively related to se verity of illness. 4. The results provide evidence that the pathophysi ology underlying the abnormal DST+CRH and DST tests in melancholia is localized at the pituitary level and may consist of a CRH-driven break through of corticotropic cell secretion synergized by central and peri pheral agents, in conjunction with a decrease in glucocorticoid feedba ck suppressibility.