title: Mineralocorticoid receptor function in depressed patients and healthy individuals.
abstract: 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.
authors: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany; Department of Psychosomatic Medicine, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany. Electronic address: kim.hinkelmann@charite.de.
authors: Kim
authors: K
authors: Hinkelmann
authors: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors: Julian
authors: J
authors: Hellmann-Regen
authors: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors: Katja
authors: K
authors: Wingenfeld
authors: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors: Linn K
authors: LK
authors: Kuehl
authors: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors: Marie
authors: M
authors: Mews
authors: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors: Juliane
authors: J
authors: Fleischer
authors: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors: Isabella
authors: I
authors: Heuser
authors: Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors: Christian
authors: C
authors: Otte
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D016022:Case-Control Studies; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D011569:Psychiatric Status Rating Scales; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D006854:Hydrocortisone
keywords: Cortisol; Depression; HPA; Mineralocorticoid receptor; Spironolactone; Stress