DNA methylation in stress and depression: from biomarker to therapeutics

Acta Neuropsychiatr. 2021 Oct;33(5):217-241. doi: 10.1017/neu.2021.18. Epub 2021 Jun 21.

Abstract

Epigenetic mechanisms such as DNA methylation (DNAm) have been associated with stress responses and increased vulnerability to depression. Abnormal DNAm is observed in stressed animals and depressed individuals. Antidepressant treatment modulates DNAm levels and regulates gene expression in diverse tissues, including the brain and the blood. Therefore, DNAm could be a potential therapeutic target in depression. Here, we reviewed the current knowledge about the involvement of DNAm in the behavioural and molecular changes associated with stress exposure and depression. We also evaluated the possible use of DNAm changes as biomarkers of depression. Finally, we discussed current knowledge limitations and future perspectives.

Keywords: DNA methylation; DNA methyltransferase inhibitors; depression; epigenetics; stress.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Biomarkers / blood*
  • Brain / metabolism
  • CpG Islands
  • DNA Methylation / drug effects
  • Depression / blood
  • Depression / drug therapy*
  • Depression / genetics*
  • Epigenomics
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Male
  • Methyltransferases / antagonists & inhibitors*
  • Mice
  • Models, Animal
  • Rats
  • Rats, Wistar
  • Stress, Psychological

Substances

  • Antidepressive Agents
  • Biomarkers
  • Methyltransferases