Possible roles of DNA methylation in bipolar disorder

Abstract

Although the role of DNA sequence-based factors is implicated in bipolar disorder (BPD), traditional genetic approaches have not been very productive in the identification of causative genes. As a result, other approaches, such as epigenetics, should also be considered in the search for the molecular basis of BPD. Genomic imprinting has been suggested to play a role in disease development, as the risk ofBPD acquisition in the offspring partially depends on the sex of the disease-transmitting parent. In addition, higher parental age is associated with an increased risk of BPD in the offspring, which suggests that age-dependent alteration of DNA methylation might be involved in the etiopathogenesis of the condition. Molecular effects of drugs also support the role of epigenetics; valproate, a histone deacetylase inhibitor, is effective in the treatment of mania. Consistent with the epigenetic theory of psychiatric disease, studies of monozygotic twins discordant for BPD revealed the DNA methylation differences between siblings. Additional studies support that DNA methylation patterns at certain genes are altered in the brain tissues of bipolar disease patients. Collectively, these findings suggest that the epigenetic studies may improve our understanding of the etiology and pathogenesis of BPD. © Springer-Verlag Berlin Heidelberg 2011.