Skeletal muscle DNA methylation modifications and psychopharmacologic treatment in bipolar disorder

Eur Neuropsychopharmacol. 2019 Dec;29(12):1365-1373. doi: 10.1016/j.euroneuro.2019.10.001. Epub 2019 Oct 19.

Abstract

Both severe mental illness and atypical antipsychotics have been independently associated with insulin resistance and weight gain. Altered regulation of skeletal muscle DNA methylation may play a role. We aimed to evaluate DNA methylation modifications in human skeletal muscle samples to further understand its potential role in the metabolic burden observed in psychiatric patients and psychopharmacologic treatment. Subjects were included in our study if they had a bipolar diagnosis and were currently treated with a mood stabilizer or atypical antipsychotic. A healthy control group free of psychiatric or physical disease was also included for comparisons. Anthropometric, BMI and hemoglobin A1C (HbA1C%) were measured. Fasting skeletal muscle biopsies were obtained and methylation levels of 5-methycytosine (5-mC), 5-hydroxymethylcytosine (5-hmC) and 5-formylcytosine (5-fC) were measured. Skeletal muscle global methylation of 5-mC and 5-fC were significantly higher in bipolar subjects compared to healthy controls. 5-mC was significantly higher in the AAP group compared to the mood stabilizer group. Significant correlations were observed between 5-fC methylation and HbA1C%. Our findings suggest that psychiatric disease and treatment may influence some methylation measures in the skeletal muscle of patients with bipolar disorder, which may be further influenced by medication treatment.

Keywords: Antipsychotic; Bipolar; Methylation; Skeletal muscle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / genetics
  • Bipolar Disorder / metabolism*
  • Cross-Sectional Studies
  • DNA Methylation / drug effects
  • DNA Methylation / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Treatment Outcome

Substances

  • Antipsychotic Agents