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 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

A significant proportion of patients with schizophrenia have increased homocysteine levels that are unrelated to psychopharmacological medication or nutrient deficiency in folate or cobalamin. This supports the hypothesis that inherent methylation deficiency is involved in the pathogenesis of schizophrenia.
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PMID:Homocysteinemia is a common feature of schizophrenia. 896 86

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

Folates function as a single carbon donor in the synthesis of serine from glycine, in the synthesis of nucleotides form purine precursors, indirectly in the synthesis of transfer RNA, and as a methyl donor to create methylcobalamin, which is used in the re-methylation of homocysteine to methionine. Oral folates are generally available in two supplemental forms, folic and folinic acid. Administration of folinic acid bypasses the deconjugation and reduction steps required for folic acid. Folinic acid also appears to be a more metabolically active form of folate, capable of boosting levels of the coenzyme forms of the vitamin in circumstances where folic acid has little to no effect. Therapeutically, folic acid can reduce homocysteine levels and the occurrence of neural tube defects, might play a role in preventing cervical dysplasia and protecting against neoplasia in ulcerative colitis, appears to be a rational aspect of a nutritional protocol to treat vitiligo, and can increase the resistance of the gingiva to local irritants, leading to a reduction in inflammation. Reports also indicate that neuropsychiatric diseases secondary to folate deficiency might include dementia, schizophrenia-like syndromes, insomnia, irritability, forgetfulness, endogenous depression, organic psychosis, peripheral neuropathy, myelopathy, and restless legs syndrome.
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PMID:Folates: supplemental forms and therapeutic applications. 963 Jul 38

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

Moderate hyperhomocysteinemia is associated with several diseases, including coronary artery disease, stroke, Alzheimer's disease, schizophrenia, and spina bifida. However, the mechanisms for their pathogenesis are unknown but could involve the interaction of homocysteine or its metabolites with molecular targets such as neurotransmitter receptors, channels, or transporters. We discovered that L-homocysteine sulfinic acid (L-HCSA), L-homocysteic acid, L-cysteine sulfinic acid, and L-cysteic acid are potent and effective agonists at several rat metabotropic glutamate receptors (mGluRs). These acidic homocysteine derivatives 1) stimulated phosphoinositide hydrolysis in the cells stably expressing the mGluR1, mGluR5, or mGluR8 (plus Galpha(qi9)) and 2) inhibited the forskolin-induced cAMP accumulation in the cells stably expressing mGluR2, mGluR4, or mGluR6, with different potencies and efficacies depending on receptor subtypes. Of the four compounds, L-HCSA is the most potent agonist at mGluR1, mGluR2, mGluR4, mGluR5, mGluR6, and mGluR8. The effects of the four agonists were selective for mGluRs because activity was not discovered when L-HCSA and several other homocysteine derivatives were screened against a large panel of cloned neurotransmitter receptors, channels, and transporters. These findings imply that mGluRs are candidate G-protein-coupled receptors for mediating the intracellular signaling events induced by acidic homocysteine derivatives. The relevance of these findings for the role of mGluRs in the pathogenesis of homocysteine-mediated phenomena is discussed.
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PMID:L-homocysteine sulfinic acid and other acidic homocysteine derivatives are potent and selective metabotropic glutamate receptor agonists. 1264 61

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

Homocysteinemia has been reported to be a risk factor for dementia, depression and also schizophrenia, the latter in a gender-specific manner. We have determined homocysteine in female inpatients suffering from various psychiatric diseases to further investigate a possible association between homocysteinemia and psychiatric disorders. Homocysteine was not elevated in schizophrenic females (mean, 11.6+/-5.8 micromol/l); in accordance with previous studies, homocysteinemia could be found frequently in dementia of different aetiology (mean, 17.2+/-6.7 micromol/l), but also to a slighter extent in depressive disorders (mean, 12.9+/-3.8 micromol/l), especially in elderly subjects. We thus suggest that homocysteinemia, at least in females, is an unspecific risk factor for organic brain disorders, but not endogenous psychoses.
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PMID:Homocysteinemia in psychiatric disorders: association with dementia and depression, but not schizophrenia in female patients. 1466 12

Hyperhomocysteinemia is a risk factor for vascular and neuronal lesions often observed with concomitant high levels of homocysteic acid. In contrast to homocysteine, homocysteic acid induces calcium influx into neurons, with characteristics of an excitotoxic glutamatergic agonist at elevated concentrations. On the molecular level this is correlated to fast modifications of proteins (phosphorylation and proteolysis). Within the homocysteic acid induced molecular signature we focused in more detail on phosphorylation of two proteins implicated as risk factors in schizophrenia and neurodegeneration: Dihydropyrimidinase related protein and 14-3-3 protein isoforms. Among the identified proteins there are known chaperones and oxidative metabolism enzymes, but a few are new in context of neuronal stress: Lasp-1, a vitamin D associated factor and an expressed sequence with features of a Rho GDP dissociation inhibitor. Moreover, we detect a specific proteolytic processing of heat shock protein 70 and proteindisulfide isomerase, which is abolished by vitamins (folic acid, vitamin B12, and vitamin B6), which also decrease elevated intracellular calcium levels induced by homocysteic acid.
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PMID:Molecular analysis of homocysteic acid-induced neuronal stress. 1525 39

Homocysteine is a neurotoxic amino acid originally found to be an independent risk factor for cardiovascular and cerebral vascular disease and more recently suggested to be a risk factor for Alzheimer's disease. Several authors have observed high plasma homocysteine levels among schizophrenia patients. We reported that such high levels characterize young male schizophrenia patients. We now studied two groups of schizophrenia patients (N=41) and controls (N=29) for CSF homocysteine levels. No difference was found for CSF homocysteine levels between schizophrenia patients and controls (p=.041 for Study A and p=.52 for Study B).
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PMID:CSF homocysteine is not elevated in schizophrenia. 1565 44


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