Jae-Min Kim1, Robert Stewart2, Hee-Ju Kang3, Kyung-Yeol Bae4, Sung-Wan Kim5, Il-Seon Shin6, Young Joon Hong7, Youngkeun Ahn8, Myung Ho Jeong9, Jin-Sang Yoon10. 1. Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: jmkim@chonnam.ac.kr. 2. King's College London, Institute of Psychiatry, London, UK. Electronic address: r.stewart@iop.kcl.ac.uk. 3. Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: hjkang82@chonnam.ac.kr. 4. Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: kybae1@chonnam.ac.kr. 5. Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: swkim@chonnam.ac.kr. 6. Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: isshin@chonnam.ac.kr. 7. Department of Cardiology, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: hyj200@chonnam.ac.kr. 8. Department of Cardiology, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: cecilyk@chonnam.ac.kr. 9. Department of Cardiology, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: mhjeong@chonnam.ac.kr. 10. Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: jsyoon@chonnam.ac.kr.
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.
RCT Entities:
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: Laura M Hack; Gabriel R Fries; Harris A Eyre; Chad A Bousman; Ajeet B Singh; Joao Quevedo; Vineeth P John; Bernhard T Baune; Boadie W Dunlop Journal: J Affect Disord Date: 2019-02-06 Impact factor: 4.839