title: Age-associated decrease in global DNA methylation in patients with major depression.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan ; Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan.
authors.forename: Ping-Tao
authors.initials: PT
authors.lastname: Tseng
authors.affiliation: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan ; Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Pao-Yen
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chi-Fa
authors.initials: CF
authors.lastname: Hung
authors.affiliation: Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan ; Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.
authors.forename: For-Wey
authors.initials: FW
authors.lastname: Lung
authors.affiliation: Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan ; Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Cheng-Sheng
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Mian-Yoon
authors.initials: MY
authors.lastname: Chong
keywords: 5-hydroxymethylcytosine; 5-methylcytosine; antidepressant; epigenetic; gene modification; mood disorder