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).

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-hydroxymethylcytosine; 5-methylcytosine; antidepressant; epigenetic; gene modification; mood disorder.

Figure 1

Subject recruitment procedure in current study. Abbreviations: CHQ, Chinese Health Questionnaire; DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders 4th edition text revision; HAM-D, Hamilton Rating Scale for Depression; MDD, major depressive disorder.

Figure 2

(A) 5-methylcytosine (5-mc) and (B) 5-hydroxymethylcytosine (5-hmc) levels in patients with severe major depressive disorder (MDD), remitted MDD, and healthy controls, divided by sex (n=30 in males and n=44 in females). Notes: The error bars are shown as standard deviations. The asterisks express significant difference from controls. *P<0.05, and **P<0.01.

Figure 3

(A) 5-methylcytosine (5-mc) and (B) 5-hydroxymethylcytosine (5-hmc) levels in patients with severe major depressive disorder (MDD), remitted MDD, and healthy controls, in different age groups (n=14 for younger group, n=29 for middle-age group, and n=31 for older age group). Notes: Stratification of age groups are as follows: equal to or below 35 years of age, between 36 years and 50 years, and over 50 years. The error bars are shown as standard deviations. The asterisks denote significant difference from controls. *P<0.05 and **P<0.01.

Figure 4

Scatterplots of the correlation between (A) 5-methylcytosine (5-mc) levels, and (B) 5-hydroxymethylcytosine (5-hmc) levels and the severity of depressive symptoms shown as HAM-D. Notes: Pearson’s correlation r=−0.360, P=0.011 for 5-mc and r=−0.058, P=0.690 for 5-hmc. Abbreviation: HAM-D, Hamilton Depression Rating Scale.