A multivariate study of simultaneous escape from suppression by dexamethasone of urinary free cortisol, plasma cortisol, adrenocorticotropic hormone and β‐endorphin in melancholic patients

Abstract

To investigate the relationships between pre- and postdexamethasone hypothalamic-pituitary-adrenal (HPA) axis functioning in depression, we measured the levels of baseline and postdexamethasone urinary free cortisol (UFC), plasma cortisol, adrenocorticotropic hormone (ACTH) and beta-endorphin. We found that dexamethasone significantly suppressed all hormone levels. All 4 postdexamethasone hormones--but not their baseline levels--were significantly higher in melancholic subjects than in minor and simple major depressives. We have accumulated evidence that the melancholic and minor depression groups form discrete classes in postdexamethasone HPA axis hormone levels; this supports the biological heterogeneity hypothesis of melancholia. We found that a combination of the postdexamethasone UFC and beta-endorphin values yielded the most significant diagnostic tool for melancholia. Our results suggest that the measurements of both hormones may constitute the most accurate index reflecting the HPA axis escape from suppression by dexamethasone in melancholia. By means of pathway analysis, we determined the causal relationships between age, dexamethasone circulating levels, diagnostic depression classification and the various baseline and postdexamethasone hormone values.

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.…”

“…Other studies also report a suppression of plasma 13-endorphin levels by dexamethasone (Krantz and Brown 1985;Gispen-de-Wied et al 1987). 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.…”

“…One of the most consistently reported signs of HPAaxis hyperactivity in major depression is the failure to suppress plasma adrenocorticotropic hormone (ACTH) and cortisol following the overnight 1 mg dexamethasone suppression test (Carroll 1980;Maes et al 1989Maes et al , 1991b. Because highly significant positive relationships were detected between postdexamethasone (DST) intact ACTH and cortisol in major depression, it has been suggested that the pathological escape of cortisol from suppression by dexamethasone is determined, in part, by that in pituitary ACTH (Maes et al 1991b(Maes et al , 1993.…”

Effects of Hypericum perforatum on Levels of 5-Hydroxytryptamine, Noradrenaline and Dopamine in the Cortex, Diencephalon and Brainstem of the Rat

“…On the cortex, both EFFECTS OF HYPERICUM PERFORATUM ON NEUROTRANSMITTERS hypericum extracts have similar effects, whereas changes in the 5-HT and noradrenaline content of the brainstem and diencephalon suggest other considerations. Increased activity of the hypo-thalamic±pituitary±adrenal axis in depression has been reported (Maes et al 1991) and it has also been proposed that abnormality of monoamine function plays a role in the pathogenesis of this disorder (Mokrani et al 1997). This disturbance is related to central corticotropin-releasing hormone hypersecretion (Holsboer et al 1992) and subsensitivity in negative feedback by glucocorticoids (Gomez et al 1998).…”

Ultrasensitive Assay for Measuring the Intact (1–39) ACTH Molecule: An Asset in Depression Research

“…In addition, the detection limit of the ultrasensi tive intact ACTH assay is 1 pg/ml, whereas previous assays had a sensitivity between 8 and 20 pg/ml [4][5][6][7]. In our previous studies, we have suggested that the type of ACTH assay employed to measure ACTH, i.e., intact [6,7] versus nonintact ACTH [4,5] may determine the clini cal relevance for the pathophysiology of major depression and DST cortisol nonsuppression. First, post-DST intact ACTH -but not nonintact ACTH -values are able to discriminate melancholia from minor depression and the healthy state.…”