(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Depressive-Disorder--Major

It has been hypothesized that abnormal negative feedback of cortisol release in major depressive disorder (MDD) may involve impaired central glucocorticoid receptor (GR) function. Beclomethasone-induced vasoconstriction (BIV) was recently used to test the hypothesis that impaired GR function generalizes to peripheral tissues, and it was reported that BIV was decreased in medicated patients with MDD. The objective was to test the hypothesis that BIV would be reduced in unmedicated women with MDD compared with healthy controls.. Case-control.. A university womens' mental health research unit.. Women aged 18-65 years (n=19) diagnosed, according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, with MDD after a structured interview and clinical assessment. Healthy women pair-matched for age, reproductive and smoking status.. BIV was tested using a range of beclomethasone dipropionate concentrations (1-100 microg/mL) applied to the forearm, with vasoconstriction scored visually after 15-18 hours by raters blinded to diagnosis and the randomization of the application sites.. Visual scores for BIV at each beclomethasone concentration.. No significant differences between patients with MDD and controls were found. Postmenopausal women showed less of a response than premenopausal women or women taking sex-hormone preparations.. The study did not concur with the previous finding that BIV is decreased in MDD. Further research is needed to determine whether the difference in findings is due to medication or to other factors that may have distinguished the samples, including sex, age, reproductive status, illness severity, treatment resistance and setting.

Topics: Adolescent; Adult; Aged; Beclomethasone; Depressive Disorder, Major; Dose-Response Relationship, Drug; Feedback; Female; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Matched-Pair Analysis; Middle Aged; Pituitary-Adrenal System; Postmenopause; Receptors, Glucocorticoid; Skin; Vasoconstriction

Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been frequently described in depression. Due to the closed-loop nature of the HPA axis, one possible cause of this overactivity may be a defect in negative feedback regulation, in particular an abnormality of the glucocorticoid receptor (GR). In the present study, the vasoconstrictor response to the topical glucocorticoid, beclomethasone, was used to examine GR function in depression. Topical beclomethasone was applied in four concentrations (10 microl each of 3, 10, 30 and 100 microg/ml) to the forearms of 22 subjects with major depression and their age- and sex-matched controls. Skin blanching responses were compared between the depressed and control groups and, within the depressed group, on the basis of the modified dexamethasone suppression test (DST), between cortisol suppressors and non-suppressors. Depressed subjects demonstrated a significantly reduced vasoconstrictor response compared to controls (P=0.0001). No difference was detected between cortisol suppressors and non-suppressors in their skin blanching responses. These findings suggest that peripheral GR function is abnormal in depression but that the reduced vasoconstrictor response to beclomethasone is not necessarily a secondary effect of hypercortisolaemia or HPA axis overactivity.

Topics: Administration, Topical; Adult; Aged; Beclomethasone; Depressive Disorder, Major; Dose-Response Relationship, Drug; Feedback; Female; Forearm; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Receptors, Glucocorticoid; Vasoconstriction