Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of a folate-responsive psychosis that was associated with a defect in N5-10-methylenetetrahydrofolate reductase (methylene reductase) suggested the need to examine whether abnormally low activity of this enzyme might be of etiological importance in schizophrenia. We now report that there were no statistically significant differences in the platelet methylene reductase activity of chronic schizophrenics, compared with either hospitalized or nonhospitalized age-matched control subjects. Although it is possible that a larger survey might reveal a subpopulation of schizophrenics who are characterized by abnormal methylene reductase activity, this study suggests that chronic schizophrenia is not generally associated with such changes.
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PMID:Platelet methylene reductase activity in schizophrenia. 87 76

A 27-year-old woman is described whose disorder meets the DSM-III-R criteria for a diagnosis of schizophrenia and who was found to have a significantly increased serum level of homocysteine. Repeatedly, she improved on frequent cobalamin injections and deteriorated in periods without treatment. The effects of prolonged weekly treatment appeared to diminish as time went on, suggesting that the abnormality was not wholly cobalamin-dependent. It was found that methylenetetrahydrofolate reductase (MR) activity in cultured skin fibroblasts was reduced to a magnitude that is found among people with heterozygous deficiency. A defect in MR activity indicates a deficiency in methyltetrahydrofolate (MTHF), with a consequent reduction of the remethylation of homocysteine to methionine. Thus, reduced methylation may explain the increased levels of homocysteine and the transient effects of cobalamin treatment in the patient. Theoretically, MTHF should be the optimal treatment for her. The case reported highlights the importance of assessing the serum homocysteine level in order to detect methylation deficiency in patients with schizophrenia.
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PMID:Homocysteinemia and schizophrenia as a case of methylation deficiency. 773 11

Patients with methylenetetrahydrofolate reductase (MTHFR) deficiency often show psychiatric manifestations. Since a common variant of the MTHFR gene, T677(Ala), responsible for the thermolabile MTHFR with less than 50% specific MTHFR activity, has been reported, we examined whether the T677 allele is associated with psychiatric disorders in an unrelated Japanese population consisting of 297 schizophrenics, 32 patients with major depression, 40 patients with bipolar disorder, and 419 controls. The genotype homozygous for the T677 allele was significantly frequently observed in schizophrenics with an odds ratio of 1.9 (P = 0.0006), and in patients with major depression with an odds ratio of 2.8 (P = 0.005). Our data suggest associations of the MTHFR gene variant with schizophrenia and depression in the Japanese.
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PMID:Methylenetetrahydrofolate reductase variant and schizophrenia/depression. 934 5

The gene for methylenetetrahydrofolate reductase (MTHFR) has shown polymorphism in the general human population. In its homozygous form, a C677T mutation occurs in more than 5% of the grown-up population and produces a thermolabile variant which reduces the overall enzyme activity to less than 30% of normal. We investigated patients with schizophrenia-like psychosis. If hyperhomocysteinemic, their DNA-genotype for thermolabile C677T mutation was determined. Seven of 11 patients, six males and one female, were homozygous for thermolabile MTHFR. One male patient was heterozygous and all three normal homozygotes were females. In the patients who were homozygous for the C677T mutation, the homocysteine concentrations did not respond to vitamin B12 but were normalized by folate supplementation. In the normal homozygotes, however, the homocysteine concentrations were reduced by vitamin B12 alone. Our results suggest that homozygosity for thermolabile MTHFR is a risk factor for schizophrenia-like psychosis. Possibly, this risk may be reduced by folate supplementation.
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PMID:Homozygous thermolabile methylenetetrahydrofolate reductase in schizophrenia-like psychosis. 945 25

A common missense mutation of the methylenetetrahydrofolate reductase (MTHFR) gene (C677T) has been shown to be a risk factor for premature cardiovascular disease and neural tube defect. Deficient activity of MTHFR has also been implicated in the pathogenesis of psychiatric conditions such as schizophrenia and affective disorders. Arinami et al found an increased frequency of homozygosity for the mutated type (T677) of the MTHFR gene in schizophrenia and depression. We tried to replicate this finding in a sample of 343 patients with schizophrenia, 143 with bipolar disorder, 71 with unipolar depression, and 258 controls; however, there was no significantly increased frequency of homozygosity for the T677 allele in any of the diagnostic groups, compared to the controls. Our results suggest that homozygosity for the T677 allele of the MTHFR gene is unlikely to play a major role in the pathogenesis of schizophrenia or affective disorders in our sample.
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PMID:C677T polymorphism in methylenetetrahydrofolate reductase gene and psychoses. 1020 43

Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associated with schizophrenia. Homozygosity for the T677 allele of the methylenetetrahydrofolate reductase (MTHFR) gene, which encodes for a thermolabile enzyme associated with hyperhomocysteinemia, has been found to be increased in schizophrenic patients. We have investigated whether plasma homocysteine concentration and the frequency of C677T MTHFR variant were increased in schizophrenic inpatients of a psychiatric hospital (n=210) compared with controls (n=218). There were no significant differences in plasma homocysteine concentrations between the schizophrenia and the control group. The distributions of T allele and TT genotype frequencies were similar in both groups (40% and 15%). These results show that impaired homocysteine metabolism is unlikely in schizophrenia.
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PMID:Plasma homocysteine and the methylenetetrahydrofolate reductase C677T gene variant: lack of association with schizophrenia. 1042 70

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. Compared to non-responders, schizophrenic patients who are responders to neuroleptic medications are characterized by a high female/male ratio, a better long-term outcome and more frequently disturbed dopamine neurotransmission. 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 and was previously associated with schizophrenia. 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. 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.
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PMID:Association between the methylenetetrahydrofolate reductase 677C-->T missense mutation and schizophrenia. 1088 37

To investigate the role of methylenetetrahydrofolate reductase gene polymorphisms in schizophrenia, we analyzed the genotypes of MTHFR677 and MTHFR1298 of 130 schizophrenic patients and 226 controls, using a polymerase chain reaction restriction fragment length polymorphism method. The MTHFR T677 allele was significantly distributed (chi(2)=7.900; P=0.019), between schizophrenic cases and healthy controls. The T677T genotype was overrepresented in the schizophrenic patients (OR=2.504; 95% CI=1.276-4.915; chi(2)=7.477; P=0.006). The T677T/A1298A, and C677T/C1298C compound genotypes were greater in the schizophrenic patients (OR=3.157; 95% CI=1.522-6.545; chi(2)=10.336; P=0.001 and OR=1.744; 95% CI=0.108-28.121; chi(2)=0.158; P=0.691, respectively). The MTHFR T677 allele and T677T and T677T/A1298A genotypes are genetic risk factors for schizophrenia.
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PMID:Methylenetetrahydrofolate reductase gene polymorphisms in patients with schizophrenia. 1449 87

Two apparently unrelated disorders, neural tube defects (NTD) and schizophrenia showed increased risks in birth cohorts exposed to famine during early gestation. NTD is associated with impaired folate metabolism. We investigated whether schizophrenia is also linked with a dysfunctional folate metabolism. In addition to the prevalence of the 677C-->T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, we compared plasma and red blood cell (RBC) folate, vitamin B6, vitamin B12, and homocysteine (Hcy) concentrations of 35 schizophrenic patients with those of 104 unrelated controls. Schizophrenic patients had significantly lower plasma folate concentrations after adjustment for Hcy levels, and elevated RBC folate levels compared to controls. Vitamin B6, vitamin B12, and Hcy levels did not differ from control values. Plasma folate levels below the 10th percentile of controls were associated with an approximate 4-7-fold (before and after adjustment of folate levels for Hcy, respectively) risk of having schizophrenia. In addition, a significant dose-response relation between plasma folate concentrations and risk for schizophrenia suggested a protective effect by high plasma folate concentrations. Elevated Hcy levels and, in line with this finding, homozygosity for the 677C-->T mutation in the MTHFR gene were not associated with an increased risk for schizophrenia. Evidence is presented suggesting that folate metabolism is disturbed in schizophrenic patients, independently of Hcy.
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PMID:Homocysteine metabolism and B-vitamins in schizophrenic patients: low plasma folate as a possible independent risk factor for schizophrenia. 1457 19

Evidence for an involvement of aberrant homocysteine metabolism in the aetiology of schizophrenia is limited and controversial. A case-control study was performed to quantify the risk of schizophrenia in the presence of elevated homocysteine concentrations or homozygosity for the 677C --> T polymorphism (677TT) in the methylenetetrahydrofolate reductase (MTHFR) gene in subjects of Dutch ancestry. We determined the 677C --> T MTHFR genotype distribution in 254 well-defined patients and 414 healthy controls. Plasma homocysteine concentrations were measured in 62 patients with schizophrenia and 432 control subjects. When homocysteine concentrations were stratified into quartiles of the control distribution, we calculated an increased risk for schizophrenia in the fourth and third quartile versus the lowest quartile [odds ratio (OR) = 3.3; 95% confidence interval (CI): 1.2-9.2, and OR = 3.1; 95% CI: 1.2-8.0, respectively]. A significant dose-response relation of increasing homocysteine levels and increasing risk for schizophrenia was observed (P = 0.036). The 677TT genotype was associated with an OR of 1.6 [95% CI: 0.96-2.8] of having schizophrenia. Heterozygosity for the T allele compared to 677CC subjects accounted for an OR of 1.3 [95% CI: 0.91-1.8]. Elevated homocysteine levels and the MTHFR 677TT genotype are associated with an increased risk for schizophrenia. These observations support a causal relation between disturbed homocysteine metabolism and schizophrenia.
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PMID:Hyperhomocysteinemia, methylenetetrahydrofolate reductase 677TT genotype, and the risk for schizophrenia: a Dutch population based case-control study. 1580 5


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