An augmented escape of β-endorphins to suppression by dexamethasone in severely depressed patients

Stimulatory Effects of L-5-Hydroxytryptophan on Postdexamethasone β-Endorphin Levels in Major Depression

“…In the present study, there was a highly significant effect of dexamethasone administration on plasma 13-endorphin levels. This is in accordance with previous findings (Wiedemann et al 1979;Smith et al 1981;Krantz and Brown 1985;Gispen-de-Wied et al 1987;Maes et al 1990Maes et al , 1991b. The frequency of 13-endorphin nonsuppression (defined as post-DST 13-endorphin 2: 22 pg/ mL; Maes et al 1990) in the present study was rather low, that is, 13.8%, compared to that in our previous studies (e.g., Maes et al 1990Maes et al , 1991b.…”

“…The same day subjects ingested 1 mg dexamethasone at 11:00 P.M. The next day, a catheter was inserted at 7:30 A.M. and plasma was sampled at 8:00 A.M. for post-DST 13-endorphin assay (Maes et al 1990). Immediately after catheter placement, subjects ingested 200 mg L-5-HTP in nonenteric coated tablets or indistinguishable placebo.…”

“…This suppression may parallel the suppression of plasma ACTH levels following dexamethasone administration (Wiedemann et al 1979;Smith et al 1981;Maes et al 1991bMaes et al , 1994. Some (Gispen-de-Wied et al 1987;Maes et al 1990), but not all (Lin et al 1986;Ball et al 1987), found a higher escape of plasma 13-endorphin in major depressed subjects than in normal controls or DST cortisol nonsuppressors versus suppressors. In rats, it has been shown that pretreatment with dexamethasone blocks the 13-endorphin responses to mCPP and 8-OH-DPAT, a 5-HT 1 A agonist (Bagdy et al 1990).…”

Coexisting dysregulations of both the sympathoadrenal system and hypothalamic-pituitary-adrenal-axis in melancholia

“…In other words, the putative adrenergic effects on postdexamethasone HPA-axis secretion involve two factors: (1) indirect effects through enhancement of basal HPA-axis function, and (2) direct effects on the actual escape of the HPA-axis from dexamethasone suppression. Recently, we have evidenced that actual cortisol escape is in fact attributable to an augmented corticotrophic cell escape (ACTH and I3-endorphins) from suppression (Maes et al, 1990b, c). This fits in well with the central facilitating role of catecholamines in stimulating HPA axis (q.v.…”

“…One of the most consistently reported abnormal findings in melancholia is the failure to suppress plasma cortisol with the 1 mg dexamethasone suppression test (DST) (Carroll, 1980;Feinberg and Carroll, 1984;Brown and Shuey, 1980;Coppen et al, 1983;Evans et al, 1983;Maes et al, 1986aMaes et al, , 1987b. Moreover, we have observed that this pathological cortisol escape in melancholia is in fact attributable to an augmented escape of pituitary corticotropin cells from suppression by dexamethasone (Maes et al, 1990b, c). In addition, some (Carroll et al, 1976;Rubinow et al, 1984;Stokes et al, 1984;Maes, 1990a), but not all authors (Berger et al, 1982;Maes et al, 1989Maes et al, , 1990c were able to detect a moderately increased baseline HPA-axis activity (i.e.…”