BDNF methylation and depressive disorder in acute coronary syndrome: The K-DEPACS and EsDEPACS studies

Abstract

Objective: Epigenetic regulation investigated by methylation tests has been associated with pathogenesis and treatment response in depressive disorders. However, these hypotheses have rarely been tested in patients with acute coronary syndrome (ACS) vulnerable to depression. This study aimed to investigate whether brain derived neurotrophic factor (BDNF) methylation status is associated with occurrence and treatment response of depressive disorder in ACS.

Methods: Of 969 patients with recently developed ACS were recruited at baseline, 711 were followed 1 year thereafter. Depressive disorder was diagnosed according to DSM-IV criteria, and classified as baseline prevalent, and follow-up incident or persistent depressive disorder according to status at the two examinations. In addition, of 378 baseline participants with depressive disorder, 255 were randomized to a 24-week double blind trial of escitalopram (N=127) or placebo (N=128), while the remaining 123 received conventional medical treatment for ACS. BDNF methylation percentages were estimated using leukocyte DNA, and a range of demographic and clinical characteristics were evaluated as covariates.

Results: In logistic regression models, higher BDNF methylation status was independently associated with prevalent depressive disorder at baseline and with its persistence at follow-up. Escitalopram was more effective than placebo for treating depressive disorder in those with a higher methylation, and this effects lead to prevent persistent depressive disorder.

Conclusions: ACS patients with higher BDNF methylation were susceptible to early depressive disorder, and to its persistence one year later. Adequate antidepressants treatment may effective particularly in those with higher BDNF methylation and then can overcome epigenetic vulnerability for depression persistence in ACS patients. ClinicalTrial.gov identifier for the 24 week drug trial, NCT00419471.

Keywords: Acute coronary syndrome; BDNF; Depression; Epigenetics; Methylation.