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Detection of Metabolic Syndrome in Schizophrenia and Implications for Antipsychotic Therapy

Is There a Role for Folate?

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Abstract

In general, the presence of metabolic syndrome is associated with significant cardiovascular mortality and represents a growing public health concern in the USA. Patients with schizophrenia have a three times greater risk of death than the general population, with cardiovascular disease being the most common cause of this mortality. Use of atypical antipsychotics (AAPs) to treat schizophrenia contributes significantly to this cardiovascular risk. While several different clinical guidelines currently exist to monitor the metabolic consequences of AAP use, implementation is lacking. Because of under-monitoring of side effects and the lack of alternative treatment choices in schizophrenia, research has focused on identification of various biomarkers and pharmacogenomic targets to focus on the patients at greatest risk of metabolic syndrome, thus aiming to increase the efficacy and minimize the side effects of AAPs. This has led to several different lines of research. This review focuses on summarizing the differing metabolic syndrome criteria, monitoring guidelines for use of AAPs, and the role of folic acid as it relates to metabolic syndrome within the schizophrenia population. It concentrates not only on the pharmacogenomics of folic acid metabolism but also on its epigenetic interaction with the environment. From this work, genetic variation within both the methylenetetrahydrofolate reductase (MTHFR) gene and the catechol-O-methyltransferase (COMT) gene has been associated with an increased risk of metabolic syndrome in schizophrenia patients treated with AAPs. Furthermore, work on the combination of folate pharmacogenetics and epigenetics has uncovered relationships between methylation, schizophrenia disease, treatment type, and metabolic syndrome. Despite several areas of biomarker research into schizophrenia-related metabolic syndrome, translation into the clinical setting is still lacking, and further studies are needed to bridge this gap. In the future, folate supplementation may prove to be an easy and effective clinical tool for prevention and/or treatment of metabolic syndrome associated with AAP treatment, but clearly more research needs to be done in this area.

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Acknowledgments

The following funding sources were utilized for this publication: National Institute of Mental Health grant nos. NIMH R01 MH082784 and NIMH K08 MH64158; the National Institutes of Health (NIH)-National Center for Research Resources (NCCR) General Clinical Research Center (GCRC) Program (grant no. UL1RR024986); and the Chemistry Core of the Michigan Diabetes Research and Training Center (grant no. NIH5P60 DK 20572), The authors have no conflicts of interest that are directly relevant to the content of this review.

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Correspondence to Vicki L. Ellingrod.

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Burghardt, K.J., Ellingrod, V.L. Detection of Metabolic Syndrome in Schizophrenia and Implications for Antipsychotic Therapy. Mol Diagn Ther 17, 21–30 (2013). https://doi.org/10.1007/s40291-013-0017-8

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