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

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.