Schizophrenia Research
Volume 98, Issue 1 , Pages 47-54 , January 2008

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

      Affiliations

    • University of Michigan College of Pharmacy, Department of Clinical Sciences, United States
    • University of Michigan School of Medicine, Department of Psychiatry, United States
    • Corresponding Author InformationCorresponding author. The University of Michigan, College of Pharmacy, Department of Clinical, Social and Administrative Sciences, 428 Church Street, Ann Arbor, MI 48109, United States. Tel.: +1 734 615 4728.
  • ,
  • Del D. Miller

      Affiliations

    • University of Iowa Carver College of Medicine, Department of Psychiatry, United States
  • ,
  • Stephan F. Taylor

      Affiliations

    • University of Michigan School of Medicine, Department of Psychiatry, United States
  • ,
  • Jessica Moline

      Affiliations

    • University of Michigan College of Pharmacy, Department of Clinical Sciences, United States
  • ,
  • Timothy Holman

      Affiliations

    • University of Iowa Carver College of Medicine, Department of Psychiatry, United States
  • ,
  • Jane Kerr

      Affiliations

    • University of Iowa Carver College of Medicine, Department of Psychiatry, United States

Received 27 July 2007 ,Revised 18 September 2007 ,Accepted 24 September 2007.

References 

  1. Ames BN. DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat. Res. 2001;475(1–2):7–20
  2. Applebaum J, Shimon H, Sela BA, Belmaker RH, Levine J. Homocysteine levels in newly admitted schizophrenic patients. J. Psychiatr. Res. 2004;38(4):413–416
  3. Brattstrom L, Wilcken DE, Ohrvik J, Brudin L. Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis. Circulation. 1998;98(23):2520–2526
  4. Carlson C, Hornbuckle K, Delisle F, Kryzhanovskaya L, Breier A, Cavazzoni P. Diabetes mellitus and antipsychotic treatment in the United Kingdom. Eur. Neuropsychopharmacol. 2006;16(5):366–375
  5. Danesh J, Lewington S. Plasma homocysteine and coronary heart disease: systematic review of published epidemiological studies. J. Cardiovasc. Risk. 1998;5(4):229–232
  6. Friso S, Choi SW. Gene-nutrient interactions in one-carbon metabolism. Curr. Drug Metab. 2005;6(1):37–46
  7. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat. Genet. 1995;10(1):111–113
  8. Gaulin BD, Markowitz JS, Caley CF, Nesbitt LA, Dufresne RL. Clozapine-associated elevation in serum triglycerides. Am. J. Psychiatry. 1999;156(8):1270–1272
  9. Gianfrancesco F, White R, Wang RH, Nasrallah HA. Antipsychotic-induced type 2 diabetes: evidence from a large health plan database. J. Clin. Psychopharmacol. 2003;23(4):328–335
  10. Gueant JL, Gueant-Rodriguez RM, Anello G, et al. Genetic determinants of folate and vitamin b12 metabolism: a common pathway in neural tube defect and down syndrome?. Clin. Chem. Lab. Med. 2003;41(11):1473–1477
  11. Gueant-Rodriguez RM, Juilliere Y, Candito M, et al. Association of Mtrra66g polymorphism (but not of Mthfr C677t and A1298c, Mtra2756g, Tcn C776g) with homocysteine and coronary artery disease in the French population. Thromb. Haemost. 2005;94(3):510–515
  12. Guo JJ, Keck PE, Corey-Lisle PK, et al. Risk of diabetes mellitus associated with atypical antipsychotic use among patients with bipolar disorder: a retrospective, population-based, case–control study. J. Clin. Psychiatry. 2006;67(7):1055–1061
  13. Henderson DC, Cagliero E, Gray C, et al. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: a five-year naturalistic study. Am. J. Psychiatry. 2000;157(6):975–981
  14. Henderson DC, Cagliero E, Copeland PM, et al. Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: a frequently sampled intravenous glucose tolerance test and minimal model analysis. Arch. Gen. Psychiatry. 2005;62(1):19–28
  15. Huang TL, Chen JF. Serum lipid profiles and schizophrenia: effects of conventional or atypical antipsychotic drugs in Taiwan. Schizophr. Res. 2005;80(1):55–59
  16. Kato MM, Currier MB, Gomez CM, Hall L, Gonzalez-Blanco M. Prevalence of metabolic syndrome in Hispanic and non-Hispanic patients with schizophrenia. Prim. Care Companion J. Clin. Psychiat. 2004;6(2):74–77
  17. Kempisty B, Mostowska A, Gorska I, et al. Association of 677c> T polymorphism of methylenetetrahydrofolate reductase (Mthfr) gene with bipolar disorder and schizophrenia. Neurosci. Lett. 2006;400(3):267
  18. Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG. Mthfr 677c–> T polymorphism and risk of coronary heart disease: a meta-analysis. Jama. 2002;288(16):2023–2031
  19. Lambert BL, Chou CH, Chang KY, Tafesse E, Carson W. Antipsychotic exposure and type 2 diabetes among patients with schizophrenia: a matched case–control study of California Medicaid claims. Pharmacoepidemiol. Drug Saf. 2005;14(6):417–425
  20. Lee TH, Cleeman JI, Grundy SM, et al. Executive summary of the Third Report of the National Cholesterol Education Program (Ncep) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel Iii). Jama. 2001;285(19):2486–2497
  21. Lee YS, Han DH, Jeon CM, et al. Serum homocysteine, folate level and methylenetetrahydrofolate reductase 677, 1298 gene polymorphism in Korean schizophrenic patients. Neuroreport. 2006;17(7):743–746
  22. Levine J, Stahl Z, Sela BA, Gavendo S, Ruderman V, Belmaker RH. Elevated homocysteine levels in young male patients with schizophrenia. Am J Psychiatry. 2002;159(10):1790–1792
  23. Lewis SJ, Ebrahim S, Davey Smith G. Meta-analysis of Mthfr 677c–> T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate?. Bmj. 2005;331(7524):1053
  24. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. 2005;353(12):1209–1223
  25. Maggi S, Noale M, Gallina P, et al. metabolic syndrome, diabetes, and cardiovascular disease in an elderly caucasian cohort: the Italian longitudinal study on aging. J. Gerontol., Ser. A, Biol. Sci. Med. Sci. 2006;61(5):505–510
  26. Martin YN, Salavaggione OE, Eckloff BW, Wieben ED, Schaid DJ, Weinshilboum RM. Human methylenetetrahydrofolate reductase pharmacogenomics: gene resequencing and functional genomics. Pharmacogenet Genomics. 2006;16(4):265–277
  27. Matthews RG. Methylenetetrahydrofolate reductase: a common human polymorphism and its biochemical implications. Chem. Rec. 2002;2(1):4–12
  28. McEvoy JP, Meyer JM, Goff DC, et al. Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (Catie) schizophrenia trial and comparison with national estimates from Nhanes Iii. Schizophr. Res. 2005;80(1):19–32
  29. McEvoy JP, Lieberman JA, Stroup TS, et al. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am. J. Psychiatry. 2006;163(4):600–610
  30. Moat SJ, Lang D, McDowell IF, et al. Folate, homocysteine, endothelial function and cardiovascular disease. J. Nutr. Biochem. 2004;15(2):64–79
  31. Muntjewerff JW, Blom HJ. Aberrant folate status in schizophrenic patients: what is the evidence?. Prog. Neuro-Psychopharmacol. Biol. Psychiatry. 2005;29(7):1133
  32. Muntjewerff JW, Kahn RS, Blom HJ, den Heijer M. Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis. Mol. Psychiatry. 2005;11(2):143
  33. Nasrallah HA. Metabolic findings from the Catie trial and their relation to tolerability. CNS Spectr. 2006;11(7 Suppl 7):32–39
  34. Ollendorf DA, Joyce AT, Rucker M. Rate of new-onset diabetes among patients treated with atypical or conventional antipsychotic medications for schizophrenia. MedGenMed. 2004;6(1):5
  35. Onat A, Hergenc G, Uyarel H, Can G, Ozhan H. Prevalence, incidence, predictors and outcome of type 2 diabetes in Turkey. Anadolu Kardiyol. Derg. 2006;6(4):314–321
  36. Oommen AM, Griffin JB, Sarath G, Zempleni J. Roles for nutrients in epigenetic events. J. Nutr. Biochem. 2005;16(2):74–77
  37. Osser DN, Najarian DM, Dufresne RL. Olanzapine increases weight and serum triglyceride levels. J. Clin. Psychiatry. 1999;60(11):767–770
  38. Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature. 2007;447(7143):425–432
  39. Roffman, J.L., Weiss, A.P., Purcell, S., et al., in press. Contribution of methylenetetrahydrofolate reductase (Mthfr) polymorphisms to negative symptoms in schizophrenia. Biol. Psychiatry [Epub ahead of print].
  40. Saari KM, Lindeman SM, Viilo KM, et al. A 4-fold risk of metabolic syndrome in patients with schizophrenia: the Northern Finland 1966 Birth Cohort Study. J. Clin. Psychiatry. 2005;66(5):559–563
  41. Sernyak MJ, Gulanski B, Rosenheck R. Undiagnosed hyperglycemia in patients treated with atypical antipsychotics. J. Clin. Psychiatry. 2005;66(11):1463–1467
  42. Setola E, Monti LD, Galluccio E, et al. Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia. Eur. J. Endocrinol. 2004;151(4):483–489
  43. Simpson GM. Atypical antipsychotics and the burden of disease. Am. J. Manag. Care. 2005;11:S235–S241(8 Suppl)
  44. Spivak B, Lamschtein C, Talmon Y, et al. The impact of clozapine treatment on serum lipids in chronic schizophrenic patients. Clin. Neuropharmacol. 1999;22(2):98–101
  45. Stamler JS, Osborne JA, Jaraki O, et al. Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J. Clin. Invest. 1993;91(1):308–318
  46. Tawakol A, Omland T, Gerhard M, Wu JT, Creager MA. Hyperhomocyst(E)Inemia is associated with impaired endothelium-dependent vasodilation in humans. Circulation. 1997;95(5):1119–1121
  47. Ueland PM, Refsum H, Beresford SA, Vollset SE. The controversy over homocysteine and cardiovascular risk. Am. J. Clin. Nutr. 2000;72(2):324–332
  48. van der Put NM, Gabreels F, Stevens EM, et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?. Am. J. Hum. Genet. 1998;62(5):1044–1051
  49. Volavka J, Czobor P, Sheitman B, et al. Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder. Am. J. Psychiatry. 2002;159(2):255–262
  50. Wall RT, Harlan JM, Harker LA, Striker GE. Homocysteine-induced endothelial cell injury in vitro: a model for the study of vascular injury. Thromb. Res. 1980;18(1–2):113–121
  51. Wilson PW, D'Agostino RB, Parise H, Sullivan L, Meigs JB. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation. 2005;112(20):3066–3072
  52. Wilson PW, Nam BH, Pencina M, D'Agostino RB, Benjamin EJ, O'Donnell CJ. C-reactive protein and risk of cardiovascular disease in men and women from the Framingham Heart Study. Arch. Intern. Med. 2005;165(21):2473–2478
  53. Zintzaras E. C677t and A1298c methylenetetrahydrofolate reductase gene polymorphisms in schizophrenia, bipolar disorder and depression: a meta-analysis of genetic association studies. Psychiatr. Genet. 2006;16(3):105–115
  54. Zipursky RB, Gu H, Green AI, et al. Course and predictors of weight gain in people with first-episode psychosis treated with olanzapine or haloperidol. Br. J. Psychiatry. 2005;187:537–543

PII: S0920-9964(07)00437-9

doi: 10.1016/j.schres.2007.09.030

Schizophrenia Research
Volume 98, Issue 1 , Pages 47-54 , January 2008