Metabolic syndrome and insulin resistance in schizophrenia patients receiving antipsychotics genotyped for the methylenetetrahydrofolate reductase ( MTHFR) 677C/T and 1298A/C variants

Vicki L Ellingrod; Del D Miller; Stephan F Taylor; Jessica Moline; Timothy Holman; Jane Kerr

doi:10.1016/j.schres.2007.09.030

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Metabolic syndrome and insulin resistance in schizophrenia patients receiving antipsychotics genotyped for the methylenetetrahydrofolate reductase ( MTHFR) 677C/T and 1298A/C variants

Journal article

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Metabolic syndrome and insulin resistance in schizophrenia patients receiving antipsychotics genotyped for the methylenetetrahydrofolate reductase ( MTHFR) 677C/T and 1298A/C variants

Vicki L Ellingrod, Del D Miller, Stephan F Taylor, Jessica Moline, Timothy Holman and Jane Kerr

Schizophrenia research, Vol.98(1), pp.47-54

2008

DOI: 10.1016/j.schres.2007.09.030

PMCID: PMC2271139

PMID: 17976958

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Abstract

The metabolic syndrome and insulin resistance represent growing concerns related to atypical antipsychotic (AAP) use as their incidence in the schizophrenia population is two-to-four-fold higher than the general population. Reduced methylenetetrahydrofolate reductase ( MTHFR) activity, resulting in aberrant folate metabolism and hyperhomocysteinemia, has been linked to cardiovascular disease and is unstudied in relation to AAP associated metabolic complications. To examine the relationship between MTHFR, metabolic syndrome, and insulin resistance in schizophrenia subjects receiving AAPs for ≥ 12 months. Fifty-eight subjects were included in this cross-sectional analysis and screened for the metabolic syndrome, insulin resistance and MTHFR 677C/T and 1298A/C genotype. Overall, 23 subjects (40%) met metabolic syndrome criteria. There were no differences in age, gender, race, or AAP exposure between genotype groups. For the 677 T allele carriers, 53% met metabolic syndrome criteria, compared to 23% in the CC genotype group, giving an OR = 3.7, (95% CI = 1.24–12.66, p = 0.02). Thus, for T allele subjects, the risk was almost four times greater, despite similar antipsychotic exposure. Both waist circumference and MTHFR genotype significantly predicted insulin resistance ( F = 8.35, df = 5, 51, p < 0.0001), with these two terms interacting ( F = 8.6, df = 2, p = 0.0006) suggesting that TT subjects are at greater risk for insulin resistance with increasing central adiposity, which is independent of age, gender, BMI, or metabolic syndrome diagnosis. Results should be taken cautiously due to the small sample size, but suggest the MTHFR 677C/T variant may predispose patients to AAP metabolic complications.

Schizophrenia

Antipsychotics

Metabolic syndrome

MTFHR

Folate

Pharmacogenomics

Details

Title: Subtitle: Metabolic syndrome and insulin resistance in schizophrenia patients receiving antipsychotics genotyped for the methylenetetrahydrofolate reductase ( MTHFR) 677C/T and 1298A/C variants
Creators: Vicki L Ellingrod - University of Michigan College of Pharmacy, Department of Clinical Sciences, United States
Del D Miller - University of Iowa Carver College of Medicine, Department of Psychiatry, United States
Stephan F Taylor - University of Michigan School of Medicine, Department of Psychiatry, United States
Jessica Moline - University of Michigan College of Pharmacy, Department of Clinical Sciences, United States
Timothy Holman - University of Iowa Carver College of Medicine, Department of Psychiatry, United States
Jane Kerr - University of Iowa Carver College of Medicine, Department of Psychiatry, United States
Resource Type: Journal article
Publication Details: Schizophrenia research, Vol.98(1), pp.47-54
DOI: 10.1016/j.schres.2007.09.030
PMID: 17976958
PMCID: PMC2271139
NLM abbreviation: Schizophr Res
ISSN: 0920-9964
eISSN: 1573-2509
Publisher: Elsevier B.V
Language: English
Date published: 2008
Academic Unit: Psychiatry
Record Identifier: 9984003914502771

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