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-methylcytosine
• 5-hydroxymethylcytosine
• antidepressant
• mood disorder
• gene modification
• epigenetic

Acknowledgments

We thank the patients, control subjects, and their families for participating in this study. This work was supported by the National Science Council, Taiwan (97-2321-B-182A-003-) and Chang Gung Memorial Hospital (CMRPG860271). These funding agencies had no role in the study design, collection of samples, analysis and interpretation of data, report writing, or decision to submit the article for publication.

Author contributions

PT Tseng assisted in the study design and data analyses, and wrote the initial draft. PY Lin initiated the study concept and design, interpreted statistical data, revised, and finalized the draft. CF Hung and Y Lee interviewed and assessed participants, helped with data collection, and revised the manuscript critically. FW Lung, CS Chen, and MY Chong advised in the study design, data interpretation, and critical revision. All authors read and approved the final manuscript, and agreed to be accountable for all aspects in this study.

Disclosure

The authors report no conflicts of interest in this work.