Folate, homocysteine, interleukin-6, and tumor necrosis factor alfa levels, but not the methylenetetrahydrofolate reductase C677T polymorphism, are risk factors for schizophrenia

Journal of Psychiatric Research

Volumn 44, Issue 7, 2010, Pages 441-446

  García Miss, María del Rosario ^a   Pérez Mutul, José ^a   López Canul, Belém ^a   Solís Rodríguez, Francisco ^a   Puga Machado, Luis ^b   Oxté Cabrera, Adrián ^a   Gurubel Maldonado, Jesús ^a   Arankowsky Sandoval, Gloria ^a  

^a UNIVERSIDAD AUTÓNOMA DE YUCATÁN   (Mexico)

^b U Invest y Psicofarmacologia Clin   (Mexico)

Author keywords

B vitamins; Cytokines; Homocysteine; MTHFR genotype; Schizophrenia

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); FOLIC ACID; HOMOCYSTEINE; INTERLEUKIN 6; TUMOR NECROSIS FACTOR ALPHA;

ADULT; ARTICLE; CONTROLLED STUDY; FEMALE; GENE AMPLIFICATION; GENE FREQUENCY; GENE MUTATION; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENOTYPE; HETEROZYGOSITY; HOMOZYGOSITY; HUMAN; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RISK ASSESSMENT; RISK FACTOR; SCHIZOPHRENIA; VITAMIN BLOOD LEVEL;

EID: 77952888355     PISSN: 00223956     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jpsychires.2009.10.011     Document Type: Article

References (55)

1. Allen N.C., Bagade S., McQueen M.B., Ioannidis J.P.A., Kavvoura F.K., Khoury M.J., et al. Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nature Genetics 2008, 40:827-834.
2. Amani R. Is dietary pattern of schizophrenia patients different from healthy subjects?. BioMed Central Psychiatry 2006, 7:15-19.
3. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th ed. Washington: American Psychiatric Press; 2003.
4. Arinami T., Yamada N., Yamakagua-Kobayashi K., Hamaguchi H., Toru M. Methylenetetrahydrofolate reductase variant and schizophrenia/depression. American Journal of Medical Genetics 1997, 74:526-528.
5. 2 dominance in patients with acute exacerbation of schizophrenia. Croatian Medical Journal 2005, 46:268-274.
6. Feng L.G., Song Z.W., Xin F., Hu J. Association of plasma homocysteine and methylenetetrahydrofolate reductase C677T gene variant with schizophrenia: a Chinese Han population-based case-control study. Psychiatry Research 2009, 168:205-208.
7. Ferrando I, Bobes J, Gilbert J, Soto M. Mini-international psychiatric interview, version 5.0.0 DSM-IV, 2000.
8. Fricchione G., Rogers M.P., Daly R., Vaccaro B. The role of the monocyte-macrophage in neuropsychiatric and stress disorders. Modern Aspects of Immunobiology 2001, 1:210-215.
9. Friso S., Choi S.W. Gene-nutrient interactions in one-carbon metabolism. Current Drug Metabolism 2005, 6:37-46.
10. Frosst P., Blom H.J., Milos R., Goyette R., Sheppard C.A., Matthews R.G., et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genetics 1995, 10:111-113.
11. Fuchs D., Jaeger M., Widner B., Wirleitner B., Artner-Dzworzak E., Leblhuber F. Is hyperhomocysteinemia due to oxidative depletion of folate rather than to insufficient dietary intake? Clinical Chemistry and Laboratory Medicine 2001, 9:691-694.
12. Garver D.L., Tamas R.L., Holcomb J.A. Elevated interleukin-6 in the cerebrospinal fluid of a previously delineated schizophrenia subtype. Neuropsychopharmacology 2003, 28:1515-1520.
13. Gilbody S., Lewis S., Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HUGE review. American Journal of Epidemiology 2007, 65:1-13.
14. Goff D.C., Bottiglieri T., Arning E., Shih V., Freudenreich O., Evins A.E., et al. Folate, homocysteine, and negative symptoms in schizophrenia. The American Journal of Psychiatry 2004, 161:1705-1708.
15. González-Herrera L., García-Escalante G., Castillo-Zapata I., Canto-Herrera J., Pinto-Escalante D., Díaz-Rubio F., et al. Frequency of the thermolabile variant C677T in the MTHFR gene and lack of association with neural tube defects in the State of Yucatan, Mexico. Clinical Genetics 2002, 62:394-398.
16. Goyette P., Sumner J.S., Milos R., Duncan A.R., Rosenblatt D.S., Matthews R.G., et al. Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nature Genetics 1994, 7:195-200.
17. Guéant-Rodriguez R.M., Guéant J.L., Debard R., Thirion S., Hong L.X., Bronowicki J.P., et al. Prevalence of methylenetetrahydrofolate reductase 677T and 1298C alleles and folate status: a comparative study in Mexican, West African, and European populations. The American Journal of Clinical Nutrition 2006, 83:701-707.
18. Ho P.I., Ortiz D., Rogers E., Shea T.B. Multiple aspects of homocysteine neurotoxicity: glutamate excitotoxicity, kinase hyperactivation and DNA damage. Journal of Neuroscience Research 2002, 70:694-702.
19. Holven K.B., Aukrust P., Retterstol K., Hagve T.A., Mørkrid L., Ose L., et al. Increased levels of C-reactive protein and interleukin-6 in hyperhomocysteinemic subjects. Scandinavian Journal of Clinical and Laboratory Investigation 2006, 66:45-54.
20. Jönsson E.G., Larsson K., Vares M., Hansen T., Wang A.G., Djurovic S., et al. Two methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, schizophrenia and bipolar disorder: an association study. American Journal Medical Genetics 2008, 147B:976-982.
21. Joober R., Benkelfat C., Lai S., Bloom D., Labelle A., Lalonde P. Association between the methylenetetrahydrofolate reductase 677C→T missense mutation and schizophrenia. Molecular Psychiatry 2000, 5:323-326.
22. Kempisty B., Mostowska A., Górska I., Łuczak M., Czerski P., Szczepankiewicz A., et al. Association of 677C>T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene with bipolar disorder and schizophrenia. Neuroscience Letters 2006, 400:267-271.
23. Kohn R., Levav I., Caldas de Almeida J.M., Vicente B., Andrade L., Caraveo-Anduaga J.J., et al. Mental disorders in Latin America and the Caribbean: a public health priority. Revista Panamericana de Salud Pública 2005, 18:229-240.
24. Lazzerini P.E., Selvi E., Lorenzini S., Capecchi P.L., Ghittoni R., Bisogno S., et al. Homocysteine enhances cytokine production in cultured synoviocytes from rheumatoid arthritis patients. Clinical and Experimental Rheumatology 2006, 24:387-393.
25. Levine J., Stahl Z., Sela B.A., Gavendo S., Ruderman V., Belmaker R.H. Elevated homocysteine levels in young male patients with schizophrenia. The American Journal of Psychiatry 2002, 59:1790-1792.
26. Lee Y.S., Han D.H., Jeon C.M., Lyoo I.K., Na C., Chae S.L. Serum homocysteine, folate level and methylenetetrahydrofolate reductase 677, 1298 gene polymorphism in Korean schizophrenic patients. Neuroreport 2006, 17:743-746.
27. Lewis S.J., Zammit S., Gunnell D., Smith G.D. A meta- analysis of the MTHFR C677T polymorphism and schizophrenia risk. American Journal of Medical Genetics 2005, 135B:2-4.
28. McCreadie R.G., Kell C., Connolly M., Williams S., Baxter G., Lean M., et al. Dietary improvement in people with schizophrenia. The British Journal of Psychiatry 2005, 187:346-351.
29. McMahon J.A., Green T.J., Skeaff C.M., Knight R.G., Mann J.I., Williams S.M. A controlled trial of homocysteine lowering and cognitive performance. The New England Journal of Medicine 2006, 354:2762-2764.
30. Miyamoto S., LaMantia A., Duncan G., Sullivan P., Gilmore J., Lieberman J. Recent advances in the neurobiology of schizophrenia. Molecular Interventions 2003, 3:27-39.
31. Meyer U., Nyffeler M., Engler A., Urwyler A., Schedlowsky M., Knuesel I., et al. The time of prenatal immune challenge determines the specificity of inflammation-mediates brain and behavioral pathology. Journal of Neuroscience 2006, 26:4752-4762.
32. Muntjewerff J., Van der Put N., Eskes T., Ellenbroek B., Steegers E., Blom H., et al. Homocysteine metabolism and B-vitamins in schizophrenic patients. Low plasma folate as a possible independent risk factor for schizophrenia. Psychiatry Research 2003, 121:1-9.
33. Muntjewerff J.W., Kahn R.S., Blom H.J., Heijer M. Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta- analysis. Molecular Psychiatry 2006, 11:143-149.
34. Naudin J., Capo C., Giusano B., Mège J.L., Azorin J.M. A differential role for interleukin-6 and tumor necrosis factor-alpha in schizophrenia?. Schizophrenia Research 1997, 26:227-233.
35. Perla-Kaján J., Twardoski T., Jakubowski H. Mechanisms of homocysteine toxicity in humans. Amino Acids 2007, 32:561-572.
36. Philibert R., Gunter T., Hollenbeck N., Adams W.J., Bohle P., Packer H., et al. No association of the C677T methylenetetrahydrofolate reductase polymorphism with schizophrenia. Psychiatric Genetics 2006, 16:221-223.
37. Regland B. Schizophrenia and single-carbon metabolism. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2005, 29:1124-1132.
38. Reif A., Pfuhlmann B., Lesch K. Homocysteinemia as well as methylenetetrahydrofolate reductase polymorphism are associated with affective psychoses. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2005, 29:1162-1168.
39. Ruxton G.M. The unequal variance t-test is an underused alternative to the Student's t-test and the Mann-Whitney U test. Behavioral Ecology 2006, 17:688-690.
40. Saetre P., Emilsson L., Axelsson E., Kreuger J., Lindholm E., Jazin E. Inflammation-related genes up-regulated in schizophrenia brains. BioMed Central Psychiatry 2007, 7:46-55.
41. Sambrook J., Fritsch E., Maniatis T. Molecular cloning: a laboratory manual 1989, Cold Spring Harbor Laboratory Press, Cold Spring Harbor. 2nd ed.
42. Sazci A., Ergul E., Kucukali I., Kara I., Kaya G. Association of the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene with schizophrenia. Association is significant in men but not in women. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2005, 29:1113-1123.
43. Schroecksnadel K., Frick B., Winkler C., Leblhuber F., Wirleitner B., Fuchs D. Hyperhomocysteinemia and immune activation. Clinical Chemistry and Laboratory Medicine 2003, 41:1438-1443.
44. Schroecksnadel K., Frick B., Wirleitner B., Winkler C., Schennach H., Fuchs D. Moderate hyperhomocysteinemia and immune activation. Current Pharmaceutical Biotechnology 2004, 5:107-118.
45. Shi J., Gershon E.S., Liu C. Genetic associations with schizophrenia: meta-analyses of 12 candidate genes. Schizophrenia Research 2008, 104:96-107.
46. Strous R.D., Schoenfeld Y. Schizophrenia, autoimmunity and immune system dysregulation: a comprehensive model update and revisited. Journal of Autoimmunity 2006, 27:71-80.
47. van Aken B.E., Jansen J., van Deventer S.J., Reitsma P.H. Elevated levels of homocysteine increase IL-6 production in monocytic Mono Mac 6 cells. Blood Coagulation and Fibrinolysis 2000, 11:159-164.
48. Vilella E., Virgos C., Murphy M., Martorell L., Valero J., Simó J.M., et al. Further evidence that hyperhomocysteinemia and methylenetetrahydrofolate reductase C677T and A1289C polymorphisms are not risk factors for schizophrenia. Progress in Neuropsychopharmacology and Biological Psychiatry 2005, 29:1169-1174.
49. Wang G., Dai J., Mao J., Zeng X., Yang X., Wang X. Folic acid reverses hyper-responsiveness of LPS-induced chemokine secretion from monocytes in patients with hyperhomocysteinemia. Atherosclerosis 2005, 179:395-402.
50. Zeng X.K., Remick D.G., Wang X. Homocysteine induces production of monocyte chemoattractant protein-1 and interleukin-8 in cultured human whole blood. Acta Pharmacologica Sinica 2004, 25:1419-1425.
51. Zhang X.Y., Zhou D.F., Zhang P.Y., Wu G.Y., Cao L.Y., Shen Y.C. Elevated interleukin-2, interleukin-6 and interleukin-8 serum levels in neuroleptic-free schizophrenia: association with psychopathology. Schizophrenia Research 2002, 57:247-258.
52. Zhang X.Y., Zhou D.F., Cao L.Y., Wu G.Y., Shen Y.C. Cortisol and cytokines in chronic and treatment-resistant patients with schizophrenia: association with psychopathology and response to antipsychotics. Neuropsychopharmacology 2005, 30:1532-1538.
53. Zhang L., Jin M., Hu X.S., Zhu J.H. Homocysteine stimulates nuclear factor kappa B activity and interleukin-6 expression in rat vascular smooth muscle cells. Cell Biology International 2006, 30:592-597.
54. Zieminska E., Lazarewicz J.W. Excitotoxic neuronal injury in chronic homocysteine neurotoxicity studied in vitro: the role of NMDA and group I metabotropic glutamate receptors. Acta Neurobiologiae Experimentalis (Wars) 2006, 66:301-309.
55. Zintzaras E. C677T and A1298C methylenetetrahydrofolate reductase gene polymorphisms in schizophrenia, bipolar disorder and depression: a meta-analysis of genetic association studies. Psychiatric Genetics 2006, 16:105-115.