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The enzyme 11-beta-hydroxysteroid dehydrogenase (11-beta-HSD) regulates glucocorticoid activity by converting cortisol into cortisone and vice versa. Frequent signs of major depression are elevated concentrations of circulating cortisol and ACTH. However, no information is available about the activity of 11-beta-HSD in this disorder. Therefore, we compared diurnal plasma concentrations of cortisol and cortisone and their ratios, reflecting 11-beta-HSD activity, in 25 severely depressed patients (Hamilton Depression Scale, 29 +/- 6; 14 men, 11 women, age 22-77 yr; mean, 47 +/- 16) and 30 control persons (20 men, 10 women age 23-85 yr; mean, 51 +/- 19). Cortisol and cortisone were measured at 0900 h, 1100 h, 1300 h, 2000 h, 2200 h, 0100 h, 0300 h, and 0700 h with specific RIAs after extraction. Both cortisol and cortisone concentrations were significantly increased in patients compared with controls (cortisol, 251.7 +/- 113.1 vs. 160 +/- 96.6 nmol/L; cortisone, 32.8 +/- 10.9 vs. 21.9 +/- 10.9 nmol/L). The calculated ratios of cortisol to cortisone were similar in controls and patients. Similar to cortisol, the circadian variation of cortisone was flattened in patients with the ratio of maximal cortisone to minimal cortisone being 1.9-fold higher in controls than in patients. There was no gender-specific difference in cortisone values neither in patients nor in controls. We conclude that in major depression increased cortisol is not due, at least partly, to an altered 11-beta-HSD activity or to a decrease in cortisone.

Increased Diurnal Plasma Concentrations of Cortisone in Depressed Patients