Platelet Methylene Reductase Activity in Schizophrenia

Berger, Philip A.; Elliott, Glen R.; Erdelyi, Elizabeth; Watson, Stanley J.; Wyatt, Richard Jed; Barchas, Jack D.

doi:10.1001/archpsyc.1977.01770190070006

Cited by 7 publications

(4 citation statements)

References 19 publications

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“…For schizophrenia, our results accord with the Berger et al's study 12 which found no significant difference in platelet MTHFR activity between schizophrenic and normal individuals. However, the possibility remains that the polymorphism is related to a small proportion of patients with psychoses.…”

supporting

confidence: 92%

C677T polymorphism in methylenetetrahydrofolate reductase gene and psychoses

et al. 1998

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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 1 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.Methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) catalyses the NADPH-linked reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cofactor for methylation of homocysteine to methionine and a compound which possibly serves as the methylation of biogenic amines. Frosst et al 2 identified a common mutation (C677T), which converts an alanine to a valine residue. This mutation is associated with MTHFR activity and plasma homocysteine levels; homocysteine levels in individuals homozygous for the mutated type were almost twice the value for heterozygous or homozygous for the wild-type. Furthermore, the mutation has been shown to be a risk factor for premature cardiovascular disease 3,4 and neural tube defect. 5,6 Deficient activity of MTHFR may also be associated with psychiatric conditions such as mental retardation, schizophrenia, 7-9 and affective disorders. 10 In line with this, a recent study of Arinami et al 1 examined the C677T polymorphism for patients with schizophrenia, bipolar disorder, and depression, and found an increased frequency of homozygosity for the T677 allele among schizophrenics (odds ratio 1.9, P = 0.0006) and among patients with unipolar depression (odds ratio 2.8, P = 0.005), but not among patients with bipolar disorder (odds ratio 1.0). In the present study, we tried to replicate these findings. Table 1 shows the genotype distribution and allele frequency for the C677T polymorphism of the MTHFR gene among the patients with schizophrenia, bipolar disorder, unipolar depression, and controls. The genotype distributions were in Hardy-Weinberg equilibrium for the four groups ( 2 = 0.1, df = 1, ns for the schizophrenics; 2 = 0.6, df = 1, ns for the patients with bipolar disorder; 2 = 0.7, df = 1, ns for the patients with unipolar depression; 2 = 0.9, df = 1, ns for the controls). The frequency of the T677 allele in our control subjects was 0.38, which was consistent with two other Japanese studies; Nshio et al 11 investigated 129 men aged 40-59 years and obtained an allele frequency of 0.38 and Arinami et al 1 reported 0.37 ...

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supporting

confidence: 92%

C677T polymorphism in methylenetetrahydrofolate reductase gene and psychoses

et al. 1998

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“…Methionine synthase requires methyltetrahydrofolate as methyl donor and cobalamin as cofactor. Methyltetrahydrofolate, in turn, is synthesized by the catalytic action of MR. Deficient activity of this enzyme has been associated with schizophrenia (Freeman et al, 1975;Regland et al, 1994), although such a deficiency is not a general feature of schizophrenia (Berger et al, 1977).…”

Section: Discussionmentioning

confidence: 99%

Homocysteinemia is a common feature of schizophrenia

Regland¹,

Johansson

Grenfeldt³

et al. 1995

J. Neural Transmission

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“…Our positive association with schizophrenia is, however, inconsistent with previous studies on MTHFR activity in schizophrenics and with linkage studies. MTHFR deficiency in platelets is not a general feature of schizophrenia [Berger et al, 1977;Carl et al, 1978]. However, MTHFR activity in platelets is less than one tenth and exhibits an extraordinary wide range [Berger et al, 1977;Carl et al, 1978] compared with lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

“…MTHFR deficiency in platelets is not a general feature of schizophrenia [Berger et al, 1977;Carl et al, 1978]. However, MTHFR activity in platelets is less than one tenth and exhibits an extraordinary wide range [Berger et al, 1977;Carl et al, 1978] compared with lymphocytes. Positive linkage for schizophrenia to the MTHFR locus that is assigned to 1p36.3 has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase variant and schizophrenia/depression

et al. 1997

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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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Platelet Methylene Reductase Activity in Schizophrenia

Cited by 7 publications

References 19 publications

C677T polymorphism in methylenetetrahydrofolate reductase gene and psychoses

C677T polymorphism in methylenetetrahydrofolate reductase gene and psychoses

Homocysteinemia is a common feature of schizophrenia

Methylenetetrahydrofolate reductase variant and schizophrenia/depression

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