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Homocysteine levels in schizophrenia patients newly admitted to an acute psychiatric ward

Published online by Cambridge University Press:  28 May 2015

Rosaria Di Lorenzo ,
Alessandra Amoretti ,
Samantha Baldini ,
Marcello Soli ,
Giulia Landi ,
Gabriella Pollutri ,
Rossella Corradini  and
Paola Ferri
Rosaria Di Lorenzo*
Affiliation:
Department of Mental Health, AUSL-MODENA, Servizio Psichiatrico di Diagnosi e Cura-Modena Centro, Baggiovara (Modena), Italy
Alessandra Amoretti
Affiliation:
Accredited Private Psychiatric Hospital, Villa Maria Luigia, Monticelli Terme (PR), Italy
Samantha Baldini
Affiliation:
Department of Mental Health, CPS, Viadana, ASL Mantova, Italy
Marcello Soli
Affiliation:
Department of Mental Health, Az.-USL, Corso Vallisneri, Scandiano (Reggio nell’Emilia), Italy
Giulia Landi
Affiliation:
School of Psychiatry, University of Modena and Reggio Emilia, Policlinico, Modena, Italy
Gabriella Pollutri
Affiliation:
School of Psychiatry, University of Modena and Reggio Emilia, Policlinico, Modena, Italy
Rossella Corradini
Affiliation:
AUSL-MODENA, NOCSAE, Baggiovara (Modena), Italy
Paola Ferri
Affiliation:
University of Modena and Reggio Emilia, Policlinico, Modena, Italy
*
Rosaria Di Lorenzo, rua Muro, 92, 41100 Modena, Italia. Tel: +39-059-3962320; Fax: +39-059-3961379; E-mail: [email protected]
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Abstract

Objective

After the discovery of ‘homocystinuria syndrome’, many studies have suggested that high blood levels of homocysteine may be associated with schizophrenia. The aim of this study was to analyse the association between hyperhomocysteinaemia and schizophrenia.

Methods

In a population of inpatients suffering from exacerbated schizophrenic disorders (N=100), we evaluated homocysteine levels the day after their admission to an acute psychiatric ward and compared it with that of a non-patient control group (N=110), matched for age and gender. We statistically analysed the correlation between homocysteine levels and selected variables: gender, age, years of illness and number of previous psychiatric admissions as well as Brief Psychiatric Rating Scale, Positive Negative Syndrome Scale and Global Assessment Functioning (GAF) Scores.

Results

We observed elevated homocysteine levels (an increase of 7.84 µM on average per patient) in 32% of the patients, but we did not find any statistically significant difference between the homocysteine levels of our patients and controls. Hyperhomocysteinaemia presented a positive statistically significant correlation with years of illness (p<0.005) and a negative statistically significant correlation with GAF score (p<0.001), but not with other clinical variables.

Conclusions

Hyperhomocysteinaemia, which occurred in our schizophrenia patients with poor social and relational functioning after many years of illness, could represent an effect of altered lifestyle due to psychosis, but not a specific marker for schizophrenia.

Keywords

hyperhomocysteinaemiainpatientslifestyleschizophrenia
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 27 , Issue 6 , December 2015 , pp. 336 - 344
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Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

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References

1. Carson, NA, Neill, DW. Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland. Arch Dis Child 1962;37:505–513.Google Scholar
2. Finkelstein, JD. The metabolism of homocysteine: pathways and regulation. Eur J Pediatr 1998;157:S40–S44.CrossRefGoogle Scholar
3. Griffiths, R, Grieve, A, Allen, S, Olverman, HJ. Neuronal and glial plasma membrane carrier-mediated uptake of L-homocysteate is not selectively blocked by beta-p-chlorophenylglutamate. Neurosci Lett 1992;147:175–178.Google Scholar
4. Muntjewerff, JW, Kahn, RS, Blom, HJ, Den Heijer, M. Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis. Mol Psychiatry 2006;11:143–149.CrossRefGoogle ScholarPubMed
5. Joober, R, Benkelfat, C, Lal, S et al. Association between the methylenetetrahydrofolate reductase 677C-->T missense mutation and schizophrenia. Mol Psychiatry 2000;5:323–326.Google Scholar
6. Kunugi, H, Fukuda, R, Hattori, M et al. C677T polymorphism in methylenetetrahydrofolate reductase gene and psychoses. Mol Psychiatry 1998;3:435–437.CrossRefGoogle ScholarPubMed
7. Wei, J, Hemmings, GP. Allelic association of the MTHFR gene with schizophrenia. Mol Psychiatry 1999;4:115–116.Google Scholar
8. Vilella, E, Virgos, C, Murphy, M et al. Further evidence that hyperhomocysteinemia and methylenetetrahydrofolate reductase C677T and A1289C polymorphisms are not risk factors for schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:1169–1174.Google Scholar
9. Kevere, L, Purvina, S, Bauze, D et al. Elevated serum levels of homocysteine as an early prognostic factor of psychiatric disorders in children and adolescents. Schizophr Res Treatment 2012;2012:373261.Google Scholar
10. Garcìa-Miss mdel, R, Pérez-Mutul, J, Lòpez-Canul, B et al. Folate, homocysteine, interleukin-6, and tumor necrosis factor alfa levels, but not the methylentetrahydrofolate reductase C677T polymorphism, are risk factors for schizophrenia. J Psychiatr Res 2010;44:441–446.CrossRefGoogle ScholarPubMed
11. Vares, M, Saetre, P, Deng, H et al. Association between methylentetrahydrofolate reductase (MTHFR) C677T polymorphism and age of onset in schizophrenia. Am J Med Genet B Neuropsychiatr Gene 2010;153:610–618.Google Scholar
12. Muntjewerff, JW, Gellekink, H, Den Heijer, M et al. Polymorphisms in catechol-O-methyltransferase and methylenetetrahydrofolate reductase in relation to the risk of schizophrenia. Eur Neuropsychopharmacol 2008;18:99–106.Google Scholar
13. Roffman, JL, Brohawn, DG, Nitenson, AZ, Macklin, EA, Smoller, JW, Goff, DC. Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia. Schizophr Bull 2013;39:330–338.Google Scholar
14. Van Winkel, R, Rutten, BP, Peerbooms, O, Peuskens, J, Van OS, J, De Hert, M. MTHFR and risk of metabolic syndrome in patients with schizophrenia. Schizophr Res 2010;121:193–198.CrossRefGoogle ScholarPubMed
15. Ellingrod, VL, Taylor, SF, Dalack, G et al. Risk factors associated with metabolic syndrome in bipolar and schizophrenia subjects treated with antipsychotics: the role of folate pharmacogenetics. J Clin Psychopharmacol 2012;32:261–265.Google Scholar
16. Vuksan-Cusa, B, Sagud, M, Jakovljevic, M et al. Association between C-reactive protein and homocysteine with the subcomponents of metabolic syndrome in stable patients with bipolar disorder and schizophrenia. Nord J Psychiatry 2013;67:320–325.Google Scholar
17. Sakuta, H, Suzuki, T. Alcohol consumption and plasma homocysteine. Alcohol 2005;37:73–77.CrossRefGoogle ScholarPubMed
18. Panagiotakos, DB, Pitsavos, C, Zampelas, A et al. The association between coffee consumption and plasma total homocysteine levels: the “ATTICA” study. Heart Vessels 2004;19:280–286.Google Scholar
19. Chrysohoou, C, Panagiotakos, DB, Pitsavos, C et al. The associations between smoking, physical activity, dietary habits and plasma homocysteine levels in cardiovascular disease-free people: the ‘ATTICA’ study. Vasc Med 2004;9:117–123.Google Scholar
20. Schwaninger, M, Ringleb, P, Winter, R et al. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment. Epilepsia 1999;40:345–350.CrossRefGoogle ScholarPubMed
21. Prolla, TA, Mattson, MP. Molecular mechanisms of brain aging and neurodegenerative disorders: lessons from dietary restriction. Trends Neurosci 2001;24:S21–S31.Google Scholar
22. Fruchart, JC, Nierman, MC, Stroes, ES, Kastelein, JJ, Duriez, P. New risk factors for atherosclerosis and patient risk assessment. Circulation 2004;109:15–19.CrossRefGoogle ScholarPubMed
23. Elias, MF, Sullivan, LM, D’Agostino, RB et al. Homocysteine and cognitive performance in the Framingham offspring study: age is important. Am J Epidemiol 2005;162:644–653.Google Scholar
24. Selhub, J. Public health significance of elevated homocysteine. Food Nutr Bull 2008;29:S116–S125.CrossRefGoogle ScholarPubMed
25. Kruman, II, Culmsee, C, Chan, SL et al. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 2000;20:6920–6926.Google Scholar
26. Seshadri, S, Beiser, A, Selhub, J et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002;346:476–483.Google Scholar
27. Wright, CB, Paik, MC, Brown, TR et al. Total homocysteine is associated with white matter hyperintensity volume: the Northern Manhattan Study. Stroke 2005;36:1207–1211.Google Scholar
28. Seshadri, S, Wolf, PA, Beiser, AS et al. Association of plasma total homocysteine levels with subclinical brain injury: cerebral volumes, white matter hyperintensity, and silent brain infarcts at volumetric magnetic resonance imaging in the Framingham offspring study. Arch Neurol 2008;65:642–649.Google Scholar
29. O’Suilleabhain, PE, Sung, V, Hernandez, C et al. Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations. Arch Neurol 2004;61:865–868.Google Scholar
30. Lerner, V, Miodownik, C, Kaptsan, A, Vishne, T, Sela, BA, Levine, J. High serum homocysteine levels in young male schizophrenic and schizoaffective patients with tardive parkinsonism and/or tardive diskinesia. J Clin Psychiatry 2005;66:1558–1563.Google Scholar
31. Agnati, LF, Ferré, S, Genedani, S et al. Allosteric modulation of dopamine D2 receptors by homocysteine. J Proteome Res 2006;5:3077–3083.CrossRefGoogle ScholarPubMed
32. Upchurch, GR Jr., Welch, GN, Fabian, AJ et al. Homocyst(e)ine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase. J Biol Chem 1997;272:17012–17017.CrossRefGoogle ScholarPubMed
33. Shi, Q, Savage, J, Hufeisen, S et al. L-Homocysteine sulfonic acid and other acidic homocysteine derivatives are potent and selective metabotropic glutamate receptors agonists. J Pharm Exp Ther 2003;305:131–142.Google Scholar
34. Mattson, MP, Shea, TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosc 2003;26:137–146.Google Scholar
35. Coyle, JT, Tsai, JC. NMDA receptor function, neuroplasticity, and the pathophysiology of schizophrenia. Int Rev Neurobiol 2004;59:491–515.Google Scholar
36. Brown, AS, Bottiglieri, T, Schaefer, CA et al. Elevated prenatal homocysteine levels as a risk factor for schizophrenia. Arch Gen Psychiatry 2007;64:31–39.Google Scholar
37. Kochunov, P, Hong, LE. Neurodevelopmental and neurodegenerative models of schizophrenia: white matter at the center stage. Schizophr Bull 2014;40:721–728.Google Scholar
38. Spiro, HR, Schimke, RN, Welch, JP. Schizophrenia in a patient with a defect in methionine metabolism. J Nerv Ment Dis 1965;141:285–290.Google Scholar
39. Freeman, JM, Finkelstein, JD, Mudd, SH. Folate-responsive homocystinuria and schizophrenia. A defect in methylation due to deficient 5,10-methylenetetrahydrofolate reductase activity. New Engl J Med 1975;292:491–496.CrossRefGoogle Scholar
40. Pollin, W, Cardon, PV Jr., Kety, SS. Effects of amino acid feedings in schizophrenic patients treated with iproniazid. Science 1961;133:104–105.CrossRefGoogle ScholarPubMed
41. Antun, FT, Burnett, GB, Cooper, AJ, Daly, RJ, Smythies, JR, Zealley, AK. The effects of L-methionine (without MAOI) in schizophrenia. J Psychiatr Res 1971;8:63–71.CrossRefGoogle ScholarPubMed
42. Cohen, SM, Nichols, A, Wyatt, R, Pollin, W. The administration of methionine to chronic schizophrenic patients: a review of ten studies. Biol Psychiatry 1974;8:209–225.Google Scholar
43. Regland, B, Johansson, BV, Grenfeldt, B, Hjelmgren, LT, Medhus, M. Homocysteinemia is a common feature of schizophrenia. J Neural Transm 1995;100:165–169.Google Scholar
44. Susser, E, Brown, AS, Klonowski, E, Allen, RH, Lindenbaum, J. Schizophrenia and impaired homocysteine metabolism possible association. Biol Psychiatry 1998;44:141–143.CrossRefGoogle ScholarPubMed
45. 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;159:1790–1792.Google Scholar
46. Applebaum, J, Shimon, H, Sela, BA, Belmaker, RH, Levine, J. Homocysteine levels in newly admitted schizophrenic patients. J Psychiatr Res 2004;38:413–416.Google Scholar
47. Adler Nevo, G, Meged, S, Sela, BA, Hanoch-Levi, A, Hershko, R, Weizman, A. Homocysteine levels in adolescent schizophrenia patients. Eur Neuropsychopharm 2006;16:588–591.Google Scholar
48. Haidemenos, A, Kontis, D, Gazi, A, Kallai, E, Allin, M, Lucia, B. Plasma homocysteine, folate and B12 in chronic schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:1289–1296.Google Scholar
49. Neeman, G, Blanaru, M, Bloch, B et al. Relation of plasma glycine, serine, and homocysteine levels to schizophrenia symptoms and medication type. Am J Psychiatry 2005;162:1738–1740.Google Scholar
50. Petronijević, ND, Radonjić, NV, Ivković, MD et al. Plasma homocysteine levels in young male patients in the exacerbation and remission phase of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:1921–1926.Google Scholar
51. Fisekovic, S, Serdarevic, N, Memic, A, Serdarevic, R, Sahbegovic, S, Kucukalic, A. Correlation between serum concentrations of homocysteine, folate and vitamin B12 in patients with schizophrenia. J Health Sci 2013;3:138–144.Google Scholar
52. Virgos, C, Martorell, L, Simó, JM et al. Plasma homocysteine and the methylenetetrahydrofolate reductase C677T gene variant: lack of association with schizophrenia. Neuroreport 1999;10:2035–2038.Google Scholar
53. Goff, DC, Bottiglieri, T, Arning, E et al. Folate, homocysteine, and negative symptoms in schizophrenia. Am J Psychiatry 2004;161:1705–1708.Google Scholar
54. Wysokinski, A, Kloszewska, I. Homocysteine levels in patients with schizophrenia on clozapine monotherapy. Neurochem Res 2013;38:2056–2062.Google Scholar
55. Dietrich-Muszalska, A, Malinowska, J, Olas, B et al. The oxidative stress may be induced by the elevated homocysteine in schizophrenic patients. Neurochem Res 2012;37:1057–1062.Google Scholar
56. García-Bueno, B, Bioque, M, Mac-Dowell, KS et al. Pro-/anti-inflammatory dysregulation in patients with first episode of psychosis: toward an integrative inflammatory hypothesis of schizophrenia. Schizophr Bull 2014;40:376–387.Google Scholar
57. Kinoshita, M, Numata, S, Tajima, A, Shimodera, S, Imoto, I, Ohmori, T. Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia. Epigenetics 2013;8:584–590.CrossRefGoogle ScholarPubMed
58. Bromberg, A, Levine, J, Nemetz, B, Belmaker, RH, Agam, G. No association between global leukocyte DNA methylation and homocysteine levels in schizophrenia patients. Schizophr Res 2008;101:50–57.Google Scholar
59. Stahl, Z, Belmaker, RH, Friger, M, Levine, J. Nutritional and life style determinants of plasma homocysteine in schizophrenia patients. Eur Neuropsychopharm 2005;15:291–295.Google Scholar
60. Muntjewerff, JW, Van Der Put, N, Eskes, T et al. Homocysteine metabolism and B-vitamins in schizophrenic patients: low plasma folate as a possible independent risk factor for schizophrenia. Psychiatry Res 2003;121:1–9.CrossRefGoogle ScholarPubMed
61. Levine, J, Stahl, Z, Sela, BA et al. Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry 2006;60:265–269.Google Scholar
62. Godfrey, PS, Toone, BK, Carney, MW et al. Enhancement of recovery from psychiatric illness by methyl folate. Lancet 1990;336:392–395.CrossRefGoogle Scholar
63. Akanji, AO, Ohaeri, JU, Al-Shammri, SA, Fatania, HR. Associations of blood homocysteine concentrations in Arab schizophrenic patients. Clin Biochem 2007;40:1026–1031.Google Scholar
64. Ma, YY, Shek, CC, Wong, MC et al. Homocysteine level in schizophrenia patients. Aus N Z Psychiatry 2009;43:760–765.Google Scholar
65. Narayan, SK, Verman, A, Kattimani, S, Ananthanarayanan, PH, Adithan, C. Plasma homocysteine levels in depression and schizophrenia in South Indian Tamilian population. Indian J Psychiatry 2014;56:46–53.Google Scholar
66. Nishi, A, Numata, S, Tajima, A et al. Meta-analyses of blood homocysteine levels for gender and genetic association studies of the MTHFR C677T polymorphism in schizophrenia. Schizophr Bull 2014;40:1154–1163.Google Scholar
67. Kim, TH, Moon, SW. Serum homocysteine and folate levels in Korean schizophrenic patients. Psychiatry Investig 2011;8:134–140.Google Scholar
68. Ministero del lavoro, della salute e delle politiche sociali. Classificazione delle malattie, dei traumatismi, degli interventi chirurgici e delle procedure diagnostiche e terapeutiche, Italian Version International Classification of Diseases-9th Revision-Clinical Modification (ICD-9-CM) 2007. Roma: Istituto Poligrafico e Zecca dello Stato, 2008.Google Scholar
69. WHO. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. WHO Technical Report Series 854. Geneva: World Health Organization, 1995.Google Scholar
70. Refsum, H, Smith, AD, Ueland, PM et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 2004;50:3–32.CrossRefGoogle ScholarPubMed
71. Flare, M, Mitchell, J, Doan, T et al. The Abbott IMx automated bench top immunochemistry analyser system. Clin Chem 1988;34:1726–1732.Google Scholar
72. Overall, IE, Gorham, DR. The Brief Psychiatric Rating Scale. Psychol Rep 1962;10:799–812.Google Scholar
73. Kay, SR, Fiszbein, A, Opler, LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276.CrossRefGoogle ScholarPubMed
74. Endicott, J, Spitzer, RL, Fleiss, JL, Cohen, J. The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry 1976;33:766–771.Google Scholar
75. Stata Version 12. Stata Statistical Software: Release 12. College Station, TX: Stata Corp LP 2011.Google Scholar
76. Szőke, D, Dolci, A, Russo, U, Panteghini, M. Determination of plasma homocysteine: recommendations for test requesting. Biochimica Clinica 2014;38:234–237.Google Scholar
77. Dittmann, S, Seemüller, F, Schwarz, MJ et al. Association of cognitive deficits with elevated homocysteine levels in euthymic bipolar patients and its impact on psychosocial functioning: preliminary results. Bipolar Disord 2007;9:63–70.CrossRefGoogle ScholarPubMed
78. Moustafa, AA, Hewedi, DA, Eissa, AM et al. Homocysteine levels in schizophrenia and affective disorders-focus on cognition. Front Behav Neurosci 2014;8:343.Google Scholar