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Prevalence and clinical demography of hyperhomocysteinemia in Han Chinese patients with schizophrenia

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Abstract

Previous studies have shown that high homocysteine worsens the occurrence, symptoms, and prognosis of patients with schizophrenia. The purpose of this study was to evaluate the prevalence, clinical correlation, and demographic characteristics of hyperhomocysteinemia in Han Chinese schizophrenia patients. In this study, we enrolled 330 schizophrenia patients and 190 healthy controls. Positive and Negative Syndrome Scale (PANSS) was used to evaluate the psychiatric symptoms of patients with schizophrenia. The plasma homocysteine level was measured by the enzyme cycle method and the concentration of homocysteine > 15 μmol/L was defined as hyperhomocysteinemia. The prevalence of hyperhomocysteinemia in Han Chinese schizophrenia patients and healthy controls was 55.05% and 26.98%, respectively. Schizophrenia patients with hyperhomocysteinemia had more male proportion, older age, higher smoking rate, lower HDL level, higher PANSS total score, and higher negative factor than those patients without hyperhomocysteinemia. Binary logical regression result showed that gender and age were the independent risk factors of hyperhomocysteinemia. Han Chinese patients with schizophrenia had high prevalence hyperhomocysteinemia than healthy controls, and elderly male patients have a higher risk of hyperhomocysteinemia. This study was registered in the China Clinical Trial Registration Center (chiCTR 1800017044).

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References

  1. Huang Y, Wang Y, Wang H, Liu Z, Yu X, Yan J et al (2019) Prevalence of mental disorders in China: a cross-sectional epidemiological study. Lancet Psychiatry 6(3):211–224

    PubMed  Google Scholar 

  2. Puhl MD, Mintzopoulos D, Jensen JE, Gillis TE, Konopaske GT, Kaufman MJ, Coyle JT (2015) In vivo magnetic resonance studies reveal neuroanatomical and neurochemical abnormalities in the serine racemase knockout mouse model of schizophrenia. Neurobiol Dis 73:269–274

    CAS  PubMed  Google Scholar 

  3. Allen P, Modinos G, Hubl D, Shields G, Cachia A, Jardri R et al (2012) Neuroimaging auditory hallucinations in schizophrenia: from neuroanatomy to neurochemistry and beyond. Schizophr Bull 38(4):695–703

    PubMed  PubMed Central  Google Scholar 

  4. Abu-Akel A, Shamay-Tsoory S (2011) Neuroanatomical and neurochemical bases of theory of mind. Neuropsychologia 49(11):2971–2984

    PubMed  Google Scholar 

  5. Carlsson A (2006) The neurochemical circuitry of schizophrenia. Pharmacopsychiatry 39(S1):10–14

    Google Scholar 

  6. Finkelstein JD, Martin JJ (2000) Homocysteine. Int J Biochem Cell Biol 32(4):385–389

    CAS  PubMed  Google Scholar 

  7. Obeid R, Herrmann W (2006) Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett 580(13):2994–3005

    CAS  PubMed  Google Scholar 

  8. Zieminska E, Matyja E, Kozlowska H, Stafiej A, Lazarewicz JW (2006) Excitotoxic neuronal injury in acute homocysteine neurotoxicity: role of calcium and mitochondrial alterations. Neurochem Int 48(6–7):491–497

    CAS  PubMed  Google Scholar 

  9. Zieminska E, Lazarewicz JW (2006) Excitotoxic neuronal injury in chronic homocysteine neurotoxicity studied in vitro: the role of NMDA and group I metabotropic glutamate receptors. Acta Neurobiol Exp (Wars) 66(4):301–309

    Google Scholar 

  10. Regland B, Johansson BV, Grenfeldt B, Hjelmgren LT, Medhus M (1995) Homocysteinemia is a common feature of schizophrenia. J Neural Transm/Gen Sect JNT 100(2):165–169

    CAS  Google Scholar 

  11. Liu Y, Tao H, Yang X, Huang K, Zhang X, Li C (2019) Decreased serum oxytocin and increased homocysteine in first-episode schizophrenia patients. Front Psychiatry 10:217

    PubMed  PubMed Central  Google Scholar 

  12. Ma YY, Shek CC, Wong MC, Yip KC, Ng RM, Nguyen DG, Poon TK (2009) Homocysteine level in schizophrenia patients. Aust N Zeal J Psychiatry 43:760–765

    Google Scholar 

  13. Trześniowska-Drukała B, Kalinowska S, Safranow K, Kłoda K, Misiak B, Samochowiec J (2019) Evaluation of hyperhomocysteinemia prevalence and its influence on the selected cognitive functions in patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 95:109679

    PubMed  Google Scholar 

  14. Muntjewerff JW, Kahn RS, Blom HJ, den Heijer M (2006) Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis. Mol Psychiatry 11(2):143–149

    CAS  PubMed  Google Scholar 

  15. Nishi A, Numata S, Tajima A, Kinoshita M, Kikuchi K, Shimodera S et al (2014) Meta-analyses of blood homocysteine levels for gender and genetic association studies of the MTHFR C677T polymorphism in schizophrenia. Schizophr Bull 40(5):1154–1163

    PubMed  PubMed Central  Google Scholar 

  16. Misiak B, Frydecka D, Slezak R, Piotrowski P, Kiejna A (2014) Elevated homocysteine level in first-episode schizophrenia patients—the relevance of family history of schizophrenia and lifetime diagnosis of cannabis abuse. Metab Brain Dis 29(3):661–670

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Goff DC, Bottiglieri T, Arning E, Shih V, Freudenreich O, Evins AE et al (2004) Folate, homocysteine, and negative symptoms in schizophrenia. Am J Psychiatry 161(9):1705–1708

    PubMed  Google Scholar 

  18. Petronijević ND, Radonjić NV, Ivković MD, Marinković D, Piperski VD, Đuričić BM, Paunović VR (2008) Plasma homocysteine levels in young male patients in the exacerbation and remission phase of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 32(8):1921–1926

    PubMed  Google Scholar 

  19. Levine J, Stahl Z, Sela BA, Ruderman V, Shumaico O, Babushkin I et al (2006) Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry 60(3):265–269

    CAS  PubMed  Google Scholar 

  20. Akanji AO, Ohaeri JU, Al-Shammri SA, Fatania HR (2007) Associations of blood homocysteine concentrations in Arab schizophrenic patients. Clin Biochem 40(13–14):1026–1031

    CAS  PubMed  Google Scholar 

  21. Reed T, Malinow MR, Christian JC, Upson B (1991) Estimates of heritability of plasma homocyst(e)ine levels in aging adult male twins. Clin Genet 39:425–428

    CAS  PubMed  Google Scholar 

  22. Vanderjagt DJ, Patel RJ, El-Nafaty AU, Melah GS, Crossey MJ, Glew RH (2004) High-density lipoprotein and homocysteine levels correlate inversely in preeclamptic women in northern nigeria. Acta Obstet Gynecol Scand 83:536–542

    PubMed  Google Scholar 

  23. Anderson JL, Muhlestein JB, Horne BD, Carlquist JF, Bair TL, Madsen TE, Pearson RR (2000) Plasma homocysteine predicts mortality independently of traditional risk factors and c-reactive protein in patients with angiographically defined coronary artery disease. Circulation 102:1227–1232

    CAS  PubMed  Google Scholar 

  24. Sanchez-Margalet V, Valle M, Ruz FJ, Gascon F, Mateo J, Goberna R (2002) Elevated plasma total homocysteine levels in hyperinsulinemic obese subjects. J Nutr Biochem 13:75–79

    CAS  PubMed  Google Scholar 

  25. Lin YH, Pao KY, Yang WS, Wu VC, Chen YJ, Lin YL, Tsai WS, Tsai IJ, Gau CS, Hwang JJ (2008) Waist-to-hip ratio correlates with homocysteine levels in male patients with coronary artery disease. Clin Chem Lab Med 46:125–130

    CAS  PubMed  Google Scholar 

  26. Zhong Y, Xia L, Zhao TT, Zhang YL, Zhang YL, Li WZ et al (2019) The prevalence of suicide attempts and independent demographic and clinical correlates among chronic schizophrenia patients in agricultural areas of China. Psychiatr Q 90(4):683–691

    PubMed  Google Scholar 

  27. Muntjewerff JW, Hoogendoorn ML, Kahn RS, Sinke RJ, Heijer MD, Kluijtmans LA, Blom HJ (2005) Hyperhomocysteinemia, methylenetetrahydrofolate reductase 677TT genotype, and the risk for schizophrenia: a Dutch population based case-control study. Am J Med Genet Part B Neuropsychiatric Genet 135(1):69–72

    Google Scholar 

  28. Geller V, Friger M, Sela BA, Levine J (2013) Elevated homocysteine level in siblings of patients with schizophrenia. Psychiatry Res 210(3):769–772

    CAS  PubMed  Google Scholar 

  29. Lee YS, Han DH, Jeon CM, Lyoo IK, Na C, Chae SL, Cho SC (2006) Serum homocysteine, folate level and methylenetetrahydrofolate reductase 677, 1298 gene polymorphism in Korean schizophrenic patients. NeuroReport 17(7):743–746

    CAS  PubMed  Google Scholar 

  30. Kadam PD (2016) Rectocutaneous fistula with transmigration of the suture: a rare delayed complication of vault fixation with the sacrospinous ligament. Int Urogynecol J 27(1):155–157

    PubMed  Google Scholar 

  31. Roffman JL, Weiss AP, Purcell S, Caffalette CA, Freudenreich O, Henderson DC, Bottiglieri T, Wong DH, Halsted CH, Goff DC (2008) Contribution of methylenetetrahydrofolate reductase (mthfr) polymorphisms to negative symptoms in schizophrenia. Biol Psychiatry 63:42–48

    CAS  PubMed  Google Scholar 

  32. Roffman JL, Weiss AP, Deckersbach T, Freudenreich O, Henderson DC, Purcell S, Wong DH, Halsted CH, Goff DC (2007) Effects of the methylenetetrahydrofolate reductase (mthfr) c677t polymorphism on executive function in schizophrenia. Schizophr Res 92:181–188

    PubMed  Google Scholar 

  33. Moustafa AA, Hewedi DH, Eissa AM, Frydecka D, Misiak B (2014) Homocysteine levels in schizophrenia and affective disorders—focus on cognition. Front Behav Neurosci 8:343

    PubMed  PubMed Central  Google Scholar 

  34. Lipton SA, Kim WK, Choi YB, Kumar S, D'Emilia DM, Rayudu PV, Arnelle DR, Stamler JS (1997) Neurotoxicity associated with dual actions of homocysteine at the n-methyl-d-aspartate receptor. Proc Natl Acad Sci USA 94:5923–5928

    CAS  PubMed  Google Scholar 

  35. Applebaum J, Shimon H, Sela BA, Belmaker RH, Levine J (2004) Homocysteine levels in newly admitted schizophrenic patients. J Psychiatr Res 38(4):413–416

    PubMed  Google Scholar 

  36. Dimitrova KR, DeGroot K, Myers AK, Kim YD (2002) Estrogen and homocysteine. Cardiovasc Res 53(3):577–588

    CAS  PubMed  Google Scholar 

  37. Shah S, Bell RJ, Davis SR (2006) Homocysteine, estrogen and cognitive decline. Climacteric 9(2):77–87

    CAS  PubMed  Google Scholar 

  38. Nygård O, Vollset SE, Refsum H, Stensvold I, Tverdal A, Nordrehaug JE et al (1995) Total plasma homocysteine and cardiovascular risk profile: the Hordaland Homocysteine Study. JAMA 274(19):1526–1533

    PubMed  Google Scholar 

  39. Berg K, Malinow MR, Kierulf P, Upson B (1992) Population variation and genetics of plasma homocyst(e)ine level. Clin Genet 41:315–321

    CAS  PubMed  Google Scholar 

  40. Siva A, De Lange M, Clayton D, Monteith S, Spector T, Brown MJ (2007) The heritability of plasma homocysteine, and the influence of genetic variation in the homocysteine methylation pathway. QJM Mon J Assoc Phys 100:495–499

    CAS  Google Scholar 

  41. Feng LG, Song ZW, Xin F, Hu J (2009) Association of plasma homocysteine and methylenetetrahydrofolate reductase c677t gene variant with schizophrenia: a Chinese han population-based case-control study. Psychiatry Res 168:205–208

    CAS  PubMed  Google Scholar 

  42. Kadam PD, Chuan HH (2016) Erratum to: Rectocutaneous fistula with transmigration of the suture: a rare delayed complication of vault fixation with the sacrospinous ligament. Int Urogynecol J 27:505

    PubMed  Google Scholar 

  43. Stahl Z, Belmaker RH, Friger M, Levine J (2005) Nutritional and life style determinants of plasma homocysteine in schizophrenia patients. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol 15:291–295

    CAS  Google Scholar 

  44. Schneede J, Refsum H, Ueland PM (2000) Biological and environmental determinants of plasma homocysteine. Semin Thromb Hemost 26:263–279

    CAS  PubMed  Google Scholar 

  45. Yamamoto K, Isa Y, Nakagawa T, Hayakawa T (2012) Folic acid fortification ameliorates hyperhomocysteinemia caused by a vitamin b(6)-deficient diet supplemented with l-methionine. Biosci Biotechnol Biochem 76:1861–1865

    CAS  PubMed  Google Scholar 

  46. Levine J, Stahl Z, Sela BA, Ruderman V, Shumaico O, Babushkin I, Osher Y, Bersudsky Y, Belmaker RH (2006) Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry 60:265–269

    CAS  PubMed  Google Scholar 

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Acknowledgements

Thank you to all the participants.

Funding

This study was funded by grants from the National Natural Science Foundation of China (81771449, 81801341), the Key Research and Development Projects in Anhui Province (1804h08020263), and the Scientific Research Foundation of the Institute for Translational Medicine (2017zhyx17).

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Author notes

  1. Yating Yang, Juan Wang, Zulun Xiong, and Xianhu Yao have contributed equally to this manuscript.

Authors and Affiliations

  1. Department of Psychiatry, Chaohu Hospital of Anhui Medical University, 64 North Chaohu Road, Hefei, 238000, China

    Yating Yang, Juan Wang, Yulong Zhang, Xiaoshuai Ning, Yi Zhong, Zhiwei Liu, Yelei Zhang, Tongtong Zhao, Lei Xia, Kai Zhang & Huanzhong Liu

  2. Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China

    Yating Yang, Juan Wang, Yulong Zhang, Xiaoshuai Ning, Yi Zhong, Zhiwei Liu, Yelei Zhang, Tongtong Zhao, Lei Xia, Kai Zhang & Huanzhong Liu

  3. Department of Early Intervention, Hefei Fourth People’s Hospital, Hefei, 230000, China

    Zulun Xiong

  4. Maanshan Fourth People’s Hospital, Maanshan, 243071, China

    Xianhu Yao

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  1. Yating Yang
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Correspondence to Kai Zhang or Huanzhong Liu.

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Yang, Y., Wang, J., Xiong, Z. et al. Prevalence and clinical demography of hyperhomocysteinemia in Han Chinese patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci 271, 759–765 (2021). https://doi.org/10.1007/s00406-020-01150-x

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  • DOI: https://doi.org/10.1007/s00406-020-01150-x

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