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Age-associated decrease in global DNA methylation in patients with major depression

Authors Tseng PT, Lin PY, Lee Y, Hung CF, Lung FW, Chen CS, Chong MY

Received 30 July 2014

Accepted for publication 15 October 2014

Published 10 November 2014 Volume 2014:10 Pages 2105—2114

DOI https://doi.org/10.2147/NDT.S71997

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Wai Kwong Tang

Ping-Tao Tseng,1,2,* Pao-Yen Lin,1,3,* Yu Lee,1 Chi-Fa Hung,1 For-Wey Lung,4,5 Cheng-Sheng Chen,6,7 Mian-Yoon Chong1

1Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai’s Home, Taiwan; 3Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 4Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan; 5Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; 6Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 7Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

*These authors contributed equally to this work

Background: Evidence has supported a role of DNA methylation in the pathophysiology of mood disorders. The purpose of the current study is to examine 5-methylcytosine (5-mc) and 5-hydroxymethylcytosine (5-hmc) levels in patients with major depressive disorder (MDD) at different disease states.
Methods: Forty-nine patients with MDD and 25 healthy control subjects were included. The severity in the disease was assessed by using the 17-item Hamilton Rating Scale of Depression (HAM-D) (HAM-D ≥19 for severe MDD and HAM-D ≤7 for remitted MDD). The 5-mc and 5-hmc levels in leukocyte DNA were measured using an enzyme-linked immunosorbent assay-based method.
Results: We found a significant decrease in 5-hmc and trends of decreasing 5-mc levels in patients with severe MDD compared to healthy controls (P=0.059 for 5-mc and P=0.013 for 5-hmc). The decrease in the level exists only in the older age group (P=0.035 for 5-mc and P=0.002 for 5-hmc) but not in the younger age group (P=0.077 for 5-mc and P=0.620 for 5-hmc). In addition, the 5-mc level was found to be inversely correlated with disease severity (P=0.011).
Conclusion: Our results support a decrease in global DNA methylation associated with age in patients with severe depression. Further studies are needed to clarify the role of the methylation level as a disease marker of depression and whether antidepressant treatment changes the methylation profiles.

Keywords: 5-methylcytosine, 5-hydroxymethylcytosine, antidepressant, mood disorder, gene modification, epigenetic

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