Methylation of the glucocorticoid receptor gene associated with depression in patients with acute coronary syndrome

Psychoneuroendocrinology. 2019 Mar;101:42-49. doi: 10.1016/j.psyneuen.2018.10.024. Epub 2018 Oct 29.

Abstract

Objective: The present study investigated the longitudinal effects of NR3C1 1 F exon methylation on the risk of depression following ACS and treatment outcomes.

Methods: In total, 969 patients admitted for recent ACS were recruited within 2 weeks of ACS; 711 of these patients were followed up at 1 year. Depressive disorder was diagnosed according to DSM-IV criteria and included prevalent depressive disorder at baseline and incident or persistent depressive disorder at follow-up based on depression status at the two examinations. Of the 378 baseline participants who were diagnosed with depression, 255 participated in a randomized double-blind placebo-controlled trial of escitalopram, while the remaining 123 were managed with the usual medical treatment for ACS.NR3C1 1 F exon methylation was measured using peripheral blood samples, and various demographic and clinical characteristics were assessed as covariates.

Results: Higher NR3C1 1 F exon methylation levels were independently associated with prevalent depressive disorder at baseline but not with incident or persistent depressive disorder at follow-up based on logistic regression analyses adjusted for covariates. The effects of escitalopram on the remission of depressive symptoms was not influenced by NR3C1 1 F exon methylation status in ACS patients, but a placebo effect on the remission of depressive symptoms was observed, particularly in patients with lower methylation levels.

Conclusions: ACS patients with higher NR3C1 1 F exon methylation levels were at higher risk of developing depressive disorder within 2 weeks of ACS. Additionally, adequate antidepressant treatment may be effective for the remission of depressive symptoms regardless of NR3C1 1 F exon methylation status.

Keywords: ACS; DNA methylation; Depression; NR3C1; Treatment outcome.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / complications
  • Acute Coronary Syndrome / genetics*
  • Acute Coronary Syndrome / psychology
  • Adult
  • Aged
  • Antidepressive Agents / therapeutic use
  • Citalopram / pharmacology
  • CpG Islands / genetics
  • DNA Methylation / genetics
  • Depression / genetics*
  • Depression / physiopathology
  • Depressive Disorder / diagnosis
  • Depressive Disorder / genetics
  • Double-Blind Method
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Prevalence
  • Receptors, Glucocorticoid / genetics*
  • Receptors, Glucocorticoid / metabolism
  • Risk Factors
  • Treatment Outcome

Substances

  • Antidepressive Agents
  • Glucocorticoids
  • NR3C1 protein, human
  • Receptors, Glucocorticoid
  • Citalopram