Mineralocorticoid receptor function in depressed patients and healthy individuals

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 71; pp. 183 - 188
• Main Authors: Hinkelmann, Kim, Hellmann-Regen, Julian, Wingenfeld, Katja, Kuehl, Linn K., Mews, Marie, Fleischer, Juliane, Heuser, Isabella, Otte, Christian
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 03.11.2016
• Subjects: Adult; Analysis of Variance; Area Under Curve; Case-Control Studies; Cortisol; Cross-Over Studies; Depression; Depressive Disorder, Major - metabolism; Double-Blind Method; Female; HPA; Humans; Hydrocortisone - metabolism; Male; Middle Aged; Mineralocorticoid receptor; Mineralocorticoid Receptor Antagonists - pharmacology; Psychiatric Status Rating Scales; Receptors, Mineralocorticoid - metabolism; Saliva - metabolism; Spironolactone; Spironolactone - pharmacology; Stress; Time Factors; HPA; Depression; Cortisol; Spironolactone; Mineralocorticoid receptor; Stress
• ISSN: 0278-5846; 1878-4216; 1878-4216
• DOI: 10.1016/j.pnpbp.2016.08.003

Many studies have shown disturbed glucocorticoid receptor (GR) in depressed patients. In contrast, only few studies targeted mineralocorticoid receptor (MR) function with inconclusive results. We examined the effects of the MR antagonist spironolactone on cortisol secretion in depressed patients and healthy individuals. Forty-eight unmedicated depressed patients (mean age 41.6years) and 45 age- and sex-matched healthy participants (40.7years) received the MR antagonist spironolactone (300mg) or placebo with three days apart in a randomized, double-blind, within-subject cross-over design. We measured salivary cortisol before ingestion of study medication (baseline) as well as +60min, +90min, +120min, +150min and 180min after baseline. Repeated-measures ANOVA for area under the curve (AUCg) cortisol revealed a treatment effect with higher cortisol after spironolactone and a treatment by group interaction. Post-hoc analyses revealed higher cortisol in depressed patients compared to healthy participants in the placebo condition. In the spironolactone condition, the cortisol levels were not significantly different. Potentially, impaired MR or GR signaling could be responsible for higher cortisol levels in depressed patients in the placebo condition. However, after MR blockade that increased cortisol secretion across groups leading to higher GR occupation, we found no differences between depressed patients and healthy controls. Thus, our results argue for depression-associated alterations in MR signaling rather than disturbed GR-mediated feedback inhibition. •Depressed patients exhibit higher baseline cortisol values compared to healthy individuals.•MR blockade with spironolactone increases cortisol secretion.•After MR blockade no differences regarding cortisol levels between depressed and healthy were found.•Intact GR limit cortisol secretion after MR blockade.•We argue for disturbed MR rather than GR-mediated feedback inhibition in depression.