title: DNA methylation, insulin resistance and second-generation antipsychotics in bipolar disorder.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy Practice, Wayne State University Eugene Applebaum College of Pharmacy & Health Sciences, 259 Mack Avenue, Suite 2190, Detroit, MI 48201, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Burghardt
authors.affiliation: Department of Environmental Sciences, University of Michigan School of Public Health, 6638 SPH Tower, 1415 Washington Heights, Ann Arbor, MI 48109, USA.
authors.forename: Jacyln M
authors.initials: JM
authors.lastname: Goodrich
authors.affiliation: Department of Environmental Sciences, University of Michigan School of Public Health, 6638 SPH Tower, 1415 Washington Heights, Ann Arbor, MI 48109, USA.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Dolinoy
authors.affiliation: Department of Clinical Social & Administrative Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109, USA.|Department of Psychiatry, School of Medicine, University of Michigan, 1301 Catherine, Ann Arbor, MI 48109, USA.
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Ellingrod
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged
chemical_list: D014150:Antipsychotic Agents
keywords: antipsychotic; bipolar; global DNA methylation; insulin resistance