Objective Since a poor diet is often cited as a contributor to metabolic syndrome for subjects diagnosed with bipolar disorder and schizophrenia, we sought to examine dietary intake, cigarette smoking, and physical activity in these populations and compare them with the general population. Methods Individuals diagnosed with bipolar disorder (n = 116) and schizophrenia (n = 143) were assessed for dietary intake, lifestyle habits and metabolic syndrome and compared to age, gender, and race matched subjects from the National Health and Nutrition Examination Survey (NHANES) 1999-2000. Additionally, matched subgroups within the patient populations were compared to elicit any differences. Results As expected, the metabolic syndrome rate was higher in the bipolar (33%) and schizophrenia (47%) samples compared to matched NHANES controls (17% and 11%, respectively), and not different between the patient groups. Surprisingly, both bipolar disorder and schizophrenia subjects consumed fewer total calories, carbohydrates and fats, as well as more fiber (p< 0.03), compared to NHANES controls. No dietary or activity differences between patient participants with and without metabolic syndrome were found. Schizophrenia subjects had significantly lower total and low density cholesterol levels (p< 0.0001) compared to NHANES controls. Bipolar disorder subjects smoked less (p = 0.001), exercised more (p = 0.004), and had lower BMIs (p = 0.009) compared to schizophrenia subjects. Conclusions Counter to predictions, few dietary differences could be discerned between schizophrenia, bipolar disorder, and NHANES control groups. The bipolar subjects exhibited healthier behaviors than the schizophrenia patients. Additional research regarding metabolic syndrome mechanisms, focusing on non-dietary contributions, is needed.

Atypical antipsychotics increase the risk of diabetes and cardiovascular disease through their side effects of insulin resistance and weight gain. The populations for which atypical antipsychotics are used carry a baseline risk of metabolic dysregulation prior to medication which has made it difficult to fully understand whether atypical antipsychotics cause insulin resistance and weight gain directly. The purpose of this work was to conduct a systematic review and meta-analysis of atypical antipsychotic trials in healthy volunteers to better understand their effects on insulin sensitivity and weight gain. Furthermore, we aimed to evaluate the occurrence of insulin resistance with or without weight gain and with treatment length by using subgroup and meta-regression techniques. Overall, the meta-analysis provides evidence that atypical antipsychotics decrease insulin sensitivity (standardized mean difference=-0.437, p<0.001) and increase weight (standardized mean difference=0.591, p<0.001) in healthy volunteers. It was found that decreases in insulin sensitivity were potentially dependent on treatment length but not weight gain. Decreases in insulin sensitivity occurred in multi-dose studies <13days while weight gain occurred in studies 14days and longer (max 28days). These findings provide preliminary evidence that atypical antipsychotics cause insulin resistance and weight gain directly, independent of psychiatric disease and may be associated with length of treatment. Further, well-designed studies to assess the co-occurrence of insulin resistance and weight gain and to understand the mechanisms and sequence by which they occur are required.

Objective The increasing rates of metabolic syndrome and cardiovascular disease in schizophrenia has led to investigation into their causes including atypical antipsychotics and pharmacogenetic variants. This study focuses 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 antipsychotics, undergoing a clinical assessment for endothelial function via the peripheral artery tonometry (RH-PAT) method as well as a 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 functioning. Results 203 subjects with a mean age of 46 years were included. The cohort was 36% female, 36% had metabolic syndrome and 85% were currently using atypical antipsychotics. Associations between the eNOS T−786C and worse endothelial functioning (lower RH-PAT values) were found only in schizophrenia patients without metabolic syndrome. Conclusions Our results suggest 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 and 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.

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 schizophrenia; however, additional work is required.