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

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.