Routinely accessible parameters of mineralocorticoid receptor function, depression subtypes and response prediction: a post-hoc analysis from the early medication change trial in major depressive disorder

World J Biol Psychiatry. 2022 Oct;23(8):631-642. doi: 10.1080/15622975.2021.2020334. Epub 2022 Jan 25.

Abstract

Objectives: Previous studies indicated a relationship between aldosterone, the mineralocorticoid receptor (MR), and antidepressant treatment outcome. Physiological indicators of MR function (blood pressure and electrolytes) are easily accessible and may therefore serve as useful predictors. Thus, our aim was to investigate the predictive value of peripheral MR-related markers for antidepressant treatment outcomes.

Methods: 826 MDD patients who had participated in the randomised-controlled Early Medication Change (EMC) trial were analysed. Depression severity and MR-related markers were assessed weekly. In 562 patients, genetic variation of five MR-related genes was determined.

Results: Patients with blood pressure <120mmHg showed higher depression severity (p = 0.005) than patients with blood pressure ≥120mmHg. Patients with a melancholic subtype had significantly lower blood pressures (p = 0.004). Na+/K+ ratio was positively and K+-concentration was negatively correlated to depression severity and to relative changes in HAMD from baseline to day 14, and 56 respectively (p < 0.001). For none of the MR-related genes, genetic variation was associated with treatment outcomes.

Conclusions: We confirmed early observations of an altered peripheral MR sensitivity, reflected by lower blood pressure, low K+ or high Na+/K+ ratio in patients with more severe depression. These routinely collected biomarkers may potentially be useful for risk stratification in an early stage of treatment. Trial Registration: clinicaltrials.gov Identifier: NCT00974155; https://www.clinicaltrials.gov/ct2/results?term=NCT00974155.

Keywords: Major depressive disorder; aldosterone; biomarker; mineralocorticoid receptor; treatment outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / adverse effects
  • Biomarkers
  • Depression
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / genetics
  • Humans
  • Mineralocorticoids / therapeutic use
  • Receptors, Mineralocorticoid / genetics
  • Receptors, Mineralocorticoid / therapeutic use
  • Treatment Outcome

Substances

  • Receptors, Mineralocorticoid
  • Mineralocorticoids
  • Antidepressive Agents
  • Biomarkers

Associated data

  • ClinicalTrials.gov/NCT00974155