Aim: In schizophrenia, metabolic syndrome incidence is double that of the general population, with women having a higher incidence. Pharmacogenetically regulated folic acid may be related to this risk. DNA methylation and metabolic syndrome within this group has not been previously studied. Methods: Metabolic syndrome was evaluated with fasting laboratory measurements, and dietary and lifestyle assessments. Methylation analysis used a peripheral sample for the LINE-1 assay. DNA was also genotyped for MTHFR 677C/T. Results: This analysis included 133 subjects. We found a significant relationship between LINE-1 methylation, and an interaction between MTHFR and gender, controlling for serum folate (p = 0.008). Females with the 677TT genotype had the lowest methylation (56%) compared with the other groups (75%). Conclusion: TT genotype females had the lowest methylation, which may explain metabolic syndrome gender differences in schizophrenia. Folate supplementation may be a suggested intervention within schi...

The catechol-O-methyl transferase (COMT) 158Val/Met variant has been suggested to play a role in COMT function. Epigenetic regulation of COMT may further influence the prevalence of metabolic syndrome in these patient populations. This study examined the correlation between COMT promoter methylation and metabolic syndrome in schizophrenia patients receiving atypical antipsychotic (AAP) therapy. DNA was extracted from peripheral blood samples of schizophrenia subjects screened for metabolic syndrome. Pyrosequencing was used to analyze two methylation sites of the soluble COMT (COMT-s) promoter region. Associations between AAP use, lifestyle variables, metabolic syndrome and COMT genotype with peak methylation values were analyzed. Data are reported in 85 subjects. Methylation on CpG site 1 had a mean of 79.08% (±4.71) and it was 12.43% (±1.19) on site 2. COMT genotype proved to be an indicator of COMT methylation status on site 1 (F_(2, 84)=5.78, P=0.0044) and site 2 (F_(2, 84),=3.79, P=0.027). A significant negative correlation between physical activity and COMT promoter region methylation was found in Val/Val homozygous patients (site 1: P=0.013 and site 2: P=0.019). Those homozygous for Met/Met showed a positive correlation between promoter site methylation and physical activity (site 1: P=0.027, site 2: P=0.005), and between CpG site methylation and metabolic syndrome (site 1: P=0.002; site 2: P=0.001). The results of this study suggest that COMT promoter region methylation is largely influenced by COMT genotype and that physical activity plays a significant role in epigenetic modulation of COMT.

Objective: The increasing rates of metabolic syndrome and cardiovascular disease in schizophrenia led to investigation into their causes, including atypical antipsychotics and pharmacogenetic variants. This study focused on the peripheral vasculature as a cardiovascular phenotype and the influence of atypical antipsychotics, the aberrant metabolism of nitric oxide caused by endothelial nitric oxide synthetase (eNOS) genetic variants and metabolic syndrome in a cross-sectional sample of schizophrenia subjects. Methods: Associations between eNOS genetic variants and endothelial function was assessed in a cohort of schizophrenia patients taking antipsychotic drugs, whom were undergoing a clinical assessment for endothelial function via the method of peripheral artery tonometry (RH-PAT), as well as metabolic syndrome criteria screening. Analyses were conducted on the entire cohort, then again after stratifying by metabolic syndrome, to investigate the effect of the eNOS variants and metabolic syndrome on endothelial functionality. Results: We included 203 subjects with a mean age of 46 years. The cohort was 36% female, 36% had metabolic syndrome and 85% were currently using atypical antipsychotics. We found associations between the eNOS T^-786C and worse endothelial functioning (lower RH-PAT values) only in schizophrenia patients without metabolic syndrome. Conclusions: Our results suggested that when schizophrenia patients progress to meet metabolic syndrome criteria, the genetic protection of the eNOS T^-786C variant on endothelial function is no longer seen: Other factors of this pro-inflammatory state may be overriding this effect. The results of this study need replication and the factors driving endothelial dysfunction in patients with metabolic syndrome warrant further investigation.

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 met...