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

Abstract

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.

Keywords::

• antipsychotic
• bipolar
• global DNA methylation
• insulin resistance

Financial & competing interests disclosure

This work and the authors were supported by NIMH (R01 MH082784), NIH-NCCR, GCRC Program (UL1RR024986, UL1TR000433), the Chemistry Core of the Michigan Diabetes Research and Training Center (P30DK020572, P30DK092926), the Washtenaw Community Health Organization (WCHO, Ann Arbor, Michigan), The Brain and Behavior Research Foundation (formerly NARSAD, Great Neck, New York), The Rachael Upjohn Clinical Scholars Grant, University of Michigan National Institutes of Environmental Health Sciences (NIEHS) Core Center P30 ES017885 and the Prechter Longitudinal Study of Bipolar Disorder (Ann Arbor, Michigan). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work and the authors were supported by NIMH (R01 MH082784), NIH-NCCR, GCRC Program (UL1RR024986, UL1TR000433), the Chemistry Core of the Michigan Diabetes Research and Training Center (P30DK020572, P30DK092926), the Washtenaw Community Health Organization (WCHO, Ann Arbor, Michigan), The Brain and Behavior Research Foundation (formerly NARSAD, Great Neck, New York), The Rachael Upjohn Clinical Scholars Grant, University of Michigan National Institutes of Environmental Health Sciences (NIEHS) Core Center P30 ES017885 and the Prechter Longitudinal Study of Bipolar Disorder (Ann Arbor, Michigan). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.