Homocysteinemia is a common feature of schizophrenia

Regland, Björn; Johansson, B.; Grenfeldt, B.; Hjelmgren, L T; Medhus, M

doi:10.1007/bf01271539

Cited by 92 publications

(50 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among psychiatric disorders, the association with another polymorphism of the CBS gene (844ins68) was obtained for schizophrenia and schizoaffective illness [19,20]. However, higher homocysteine levels had been described in schizophrenia a decade earlier [22] than in bipolar disorder [23]. Furthermore, a connection between the T833C (rs5742905) and 844ins68 polymorphisms in some conditions was reported [24].…”

Section: Discussionmentioning

confidence: 99%

Are Genes Connected with Homocysteine Metabolism Associated with Bipolar Disorder?

Permoda-Osip¹,

Dmitrzak‐Węglarz

Hauser

et al. 2014

Neuropsychobiology

View full text Add to dashboard Cite

Background: Increased levels of homocysteine have been observed in various psychiatric disorders, among them in schizophrenia, depression and bipolar mood disorder. Of the genes connected with homocysteine metabolism, some studies have found an association between polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and bipolar disorder. The aim of this study was to investigate a possible association between 5 polymorphisms of 4 genes coding enzymes of homocysteine metabolism and bipolar disorder. Method: A total of 120 patients with bipolar disorder (24 male, 96 female) and 167 subjects from the general population (81 male, 86 female) were included in the study. Genotyping was performed for the C677T (rs1801133) and A1298C (rs1801131) polymorphisms of the MTHFR gene, for the T833C polymorphism (rs5742905) of the cystathionine-β-synthase (CBS) gene, for the A2756G polymorphism (rs1805087) of the homocysteine methyltransferase gene, and for the A66G polymorphism (rs1801394) of the methionine synthase reductase (MTRR) gene. Results: An association with bipolar disorder was found for the T833C polymorphism (rs5742905) of the CBS gene. However, in the patient sample, the genotypes of this polymorphism were not in Hardy-Weinberg equilibrium. No relationship to bipolar disorder was obtained for the remaining polymorphisms studied. Conclusions: These results are the first suggesting a possible association between T833C polymorphism (rs5742905) of the CBS gene and bipolar disorder. We were unable to confirm an association between bipolar disorder and C677T polymorphism (rs1801133) of the MTHFR gene, as suggested in some previous studies.

show abstract

Section: Discussionmentioning

confidence: 99%

Are Genes Connected with Homocysteine Metabolism Associated with Bipolar Disorder?

Permoda-Osip¹,

Dmitrzak‐Węglarz

Hauser

et al. 2014

Neuropsychobiology

View full text Add to dashboard Cite

show abstract

“…Data for the meta-analysis were obtained from eight published case-control studies 22,[29][30][31][32][33][34][35] with a total number of 812 cases and 2113 control subjects. Figure 1 shows the ORs and 95% CIs of schizophrenia associated with a 5 mmol/l increase in measured plasma total homocysteine, separately for individual studies and for all studies when taken together.…”

Section: Homocysteine and Schizophreniamentioning

confidence: 99%

“…Susser et al 30 Regland et al 29 Muntjewerff et al 33 Muntjewerff et al 22 Goff et al 35 Virgos et al 31 Applebaum et al 34 Levine Figure 1 Odds ratios (ORs) and 95% confidence intervals (CIs) of schizophrenia for a 5 mmol/l increase in plasma total homocysteine concentration for each study separately and combined (Studies are ordered by the inverse of the s.e. of each estimate.…”

Section: Studymentioning

confidence: 99%

Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis

Muntjewerff¹,

et al. 2005

View full text Add to dashboard Cite

Elevated plasma homocysteine concentration has been suggested as a risk factor for schizophrenia, but the results of epidemiological studies have been inconsistent. The most extensively studied genetic variant in the homocysteine metabolism is the 677C4T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, resulting in reduced enzyme activity and, subsequently, in elevated homocysteine. A meta-analysis of eight retrospective studies (812 cases and 2113 control subjects) was carried out to examine the association between homocysteine and schizophrenia. In addition, a meta-analysis of 10 studies (2265 cases and 2721 control subjects) on the homozygous (TT) genotype of the MTHFR 677C4T polymorphism was carried out to assess if this association is causal. A 5 lmol/l higher homocysteine level was associated with a 70% (95% confidence interval, CI: 27-129) higher risk of schizophrenia. The TT genotype was associated with a 36% (95% CI: 7-72) higher risk of schizophrenia compared to the CC genotype. The performed meta-analyses showed no evidence of publication bias or excessive influence attributable to any given study. In conclusion, our study provides evidence for an association of homocysteine with schizophrenia. The elevated risk of schizophrenia associated with the homozygous genotype of the MTHFR 677C4T polymorphism provides support for causality between a disturbed homocysteine metabolism and risk of schizophrenia.

show abstract

“…7 Several reports indicate that a high plasma level of homocysteine may be a risk factor for various pathological conditions, such as pregnancies complicated by neural tube defects 8 or abortions 9 and has been previously reported in schizophrenic patients. 10 Casereports of treatment of hyperhomocysteinemia and psychotic symptoms using folate 11,12 have been described. Furthermore, some patients with homocysteinuria, an inborn error metabolism that can be caused by rare and severe mutations in the MTHFR gene, have exhibited schizophrenia-like symptoms in addition to severe hyperhomocysteinemia, hypomethioninemia and various neurological manifestations.…”

mentioning

confidence: 99%

Association between the methylenetetrahydrofolate reductase 677C→T missense mutation and schizophrenia

et al. 2000

View full text Add to dashboard Cite

The schizophrenia phenotype is heterogeneous with respect to clinical presentation, long-term response to medication, and outcome, possibly reflecting genetic heterogeneity and/or the presence of modifier genes. 1Compared to non-responders, schizophrenic patients who are responders to neuroleptic medications are characterized by a high female/male ratio, 2 a better longterm outcome 3 and more frequently disturbed dopamine neurotransmission.4 In this study, we compared two groups of schizophrenic patients selected on the basis of their long-term response to neuroleptics (excellent responders and non-responders) and a group of healthy volunteers, with regard to a missense mutation (677C→T) in the methylenetetrahydrofolate reductase (MTHFR) gene. This polymorphism was chosen because it is functional 5 and was previously associated with schizophrenia.6 The present study revealed a significant association between schizophrenia and allele T of this gene. This association was entirely due to an over-representation of allele T in responder patients compared to controls; nonresponder patients did not differ from controls. Genotype TT was more frequent in responder patients compared to controls, thus replicating the findings of Arinami et al.6 These results strongly suggest that the MTHFR gene is involved in the pathogenesis of schizophrenia characterized by a rapid and sustained therapeutic response to typical neuroleptics and/or a good long-term prognosis/favorable therapeutic outcome. Molecular Psychiatry (2000) 5, 323-326.In order to recruit subgroups of schizophrenic patients selected on the basis of medication response, we collected 105 patients carefully assessed for long-term outcome and responsiveness to conventional neuroleptics. The responder (n = 43) and nonresponder (n = 62) schizophrenic patients did not differ according to age and gender distributions. Controls were healthy volunteers, were significantly older and included more females. In keeping with the study design, the two groups of patients differed significantly according to the severity of psychotic symptoms at the time of evaluation, the percent of time spent as inpatients since their first contact with the psychiatric institution and their age at first contact with psychiatric care facilities (see Table 1).Compared to controls, allele T of the MTHFR gene was significantly more frequent in schizophrenic patients collapsed as one sample (R + NR) ( 2 = 5.98, df = 1, P = 0.014). The most striking finding was observed when the distribution of allelic frequencies was reanalyzed according to quality of therapeutic response to conventional neuroleptics and long-term outcome. The group of responder patients showed a highly significant increase in the frequency of allele T ( 2 = 17.52, df = 1, P = 0.00003) in contrast to the group of nonresponder patients ( 2 = 0.10, df = 1, P = 0.74). The odds ratio associated with allele T (carrying at least one allele T) in the group of responder patients was 5.86 with a 95% confidence interval of [2.19, 15.70]. The att...

show abstract

Homocysteinemia is a common feature of schizophrenia

Cited by 92 publications

References 9 publications

Are Genes Connected with Homocysteine Metabolism Associated with Bipolar Disorder?

Are Genes Connected with Homocysteine Metabolism Associated with Bipolar Disorder?

Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis

Association between the methylenetetrahydrofolate reductase 677C→T missense mutation and schizophrenia

Contact Info

Product

Resources

About