title: 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.
authors: Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: jmkim@chonnam.ac.kr.
authors: Jae-Min
authors: JM
authors: Kim
authors: King's College London, Institute of Psychiatry, London, UK. Electronic address: r.stewart@iop.kcl.ac.uk.
authors: Robert
authors: R
authors: Stewart
authors: Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: hjkang82@chonnam.ac.kr.
authors: Hee-Ju
authors: HJ
authors: Kang
authors: Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: kybae1@chonnam.ac.kr.
authors: Kyung-Yeol
authors: KY
authors: Bae
authors: Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: swkim@chonnam.ac.kr.
authors: Sung-Wan
authors: SW
authors: Kim
authors: Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: isshin@chonnam.ac.kr.
authors: Il-Seon
authors: IS
authors: Shin
authors: Department of Cardiology, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: hyj200@chonnam.ac.kr.
authors: Young Joon
authors: YJ
authors: Hong
authors: Department of Cardiology, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: cecilyk@chonnam.ac.kr.
authors: Youngkeun
authors: Y
authors: Ahn
authors: Department of Cardiology, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: mhjeong@chonnam.ac.kr.
authors: Myung Ho
authors: MH
authors: Jeong
authors: Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: jsyoon@chonnam.ac.kr.
authors: Jin-Sang
authors: JS
authors: Yoon
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000235:genetics* / Q000523:psychology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D015283:Citalopram / Q000627:therapeutic use; D019175:DNA Methylation; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D015283:Citalopram
keywords: Acute coronary syndrome; BDNF; Depression; Epigenetics; Methylation