DNA methylation, insulin resistance and second-generation antipsychotics in bipolar disorder

Aims: This study aimed to assess the effect of second-generation antipsychotic (SGA) use and insulin resistance on a global measure of DNA methylation in patients diagnosed with bipolar disorder. Materials & Methods: Subjects stable on medication (either mood stabilizer monotherapy or adjuvant SGAs) were assessed for insulin resistance. Global methylation levels were assessed in leukocyte DNA from whole blood using the Luminometric Methylation Assay. Multivariable linear regression was used to investigate the effect of insulin resistance and SGA use on DNA methylation. Results: A total of 115 bipolar I subjects were included in this study. The average age was 43.1 +/- 12.2 years and 73% were on SGAs. Average% global methylation was 77.0 +/- 3.26 and was significantly influenced by insulin resistance, SGA use and smoking. Conclusion: This is the first study to show a relationship between SGA use, insulin resistance and global DNA methylation. Further work will be needed to identify tissue- and gene-specific methylation changes.