Environmental Health and Preventive Medicine

, Volume 13, Issue 1, pp 16–24

Epigenetics in mood disorders

Special Feature Frontiers in Epigenetics Medicine


Depression develops as an interaction between stress and an individual’s vulnerability to stress. The effect of early life stress and a gene–environment interaction may play a role in the development of stress vulnerability as a risk factor for depression. The epigenetic regulation of the promoter of the glucocorticoid receptor gene has been suggested as a molecular basis of such stress vulnerability. It has also been suggested that antidepressive treatment, such as antidepressant medication and electroconvulsive therapy, may be mediated by histone modification on the promoter of the brain-derived neurotrophic factor gene. Clinical genetic studies in bipolar disorder suggest the role of genomic imprinting, although no direct molecular evidence of this has been reported. The role of DNA methylation in mood regulation is indicated by the antimanic effect of valproate, a histone deacetylase inhibitor, and the antidepressive effect of S-adenosyl methionine, a methyl donor in DNA methylation. Studies of postmortem brains of patients have implicated altered DNA meA methylation of the promoter region of membrane-bound catechol-O-methyltransferase in bipolar disorder. An altered DNA methylation status of PPIEL (peptidylprolyl isomerase E-like) was found in a pair of monozygotic twins discordant for bipolar disorder. Hypomethylation of PPIEL was also found in patients with bipolar II disorder in a case control analysis. These fragmentary findings suggest the possible role of epigenetics in mood disorders. Further studies of epigenetics in mood disorders are warranted.


Biopolar disorder DNA methylation Environment Epigenetics Mood disorders Stress vulnerability 

Copyright information

© Japanese Society for Hygiene 2008

Authors and Affiliations

  1. 1.Department of Neurology and NeurosurgeryMcGill UniversityMontrealCanada
  2. 2.Laboratory for Molecular Dynamics of Mental DisordersRIKEN Brain Science InstituteWako, SaitamaJapan

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