SynthesisMolecular psychiatry2006
Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis.
Synthesis in Molecular psychiatry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 9 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
76 citing papers in PubMed, 9 syntheses or guidelines pooled it.
- Association between MTHFR (677C>T and 1298A>C) polymorphisms and psychiatric disorder: A meta-analysis.PloS one · 2022Pooled it
- Changes of Serum Homocysteine and Vitamin B12, but Not Folate Are Correlated With Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis of Case-Control Studies.Frontiers in psychiatry · 2022Pooled it
- Nutritional Deficiencies and Clinical Correlates in First-Episode Psychosis: A Systematic Review and Meta-analysis.Schizophrenia bulletin · 2018Pooled it
- Folic acid/methylfolate for the treatment of psychopathology in schizophrenia: a systematic review and meta-analysis.Psychopharmacology · 2018Pooled it
- Methylenetetrahydrofolate reductase A1298C genetic variant& risk of schizophrenia: A meta-analysis.The Indian journal of medical research · 2017Pooled it
- Evaluation of an association between plasma total homocysteine and schizophrenia by a Mendelian randomization analysis.BMC medical genetics · 2015Pooled it
- Meta-analyses of blood homocysteine levels for gender and genetic association studies of the MTHFR C677T polymorphism in schizophrenia.Schizophrenia bulletin · 2014Pooled it
- Diagnostic and treatment implications of psychosis secondary to treatable metabolic disorders in adults: a systematic review.Orphanet journal of rare diseases · 2014Pooled it
- Different roles of MTHFR C677T and A1298C polymorphisms in colorectal adenoma and colorectal cancer: a meta-analysis.Journal of human genetics · 2007Pooled it
- Higher peripheral blood homocysteine levels are associated with schizophrenia: evidence from a case-control study and a meta-analysis.Molecular psychiatry · 2026Article
- Folate and global health: part 5. syntheses on neuropsychiatric disorders.Journal of global health · 2026Review
- Associations among homocysteine, left cortical thickness, and working memory in patients with treatment-resistant schizophrenia: preliminary findings of a cohort study.BMC psychiatry · 2026Article
- Hyperhomocysteinemia in chronic schizophrenia: prevalence, clinical correlates, and paradoxical associations with symptom severity.European archives of psychiatry and clinical neuroscience · 2026Article
- Cognitive functioning and hyperhomocysteinemia in schizophrenia.Schizophrenia research. Cognition · 2026Article
- Association of homocysteine with white matter dysconnectivity in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2024Article
- Association of Prolactin, Oxytocin, and Homocysteine With the Clinical and Cognitive Features of a First Episode of Psychosis Over a 1-Year Follow-Up.The international journal of neuropsychopharmacology · 2023Article
- Serum 5-Methyltetrahydrofolate Status Is Associated with One-Carbon Metabolism-Related Metabolite Concentrations and Enzyme Activity Indicators in Young Women.International journal of molecular sciences · 2023Article
- Abnormalities in one-carbon metabolism in young patients with psychosis.Frontiers in psychiatry · 2023Article
- Genetic impairment of folate metabolism regulates cortical interneurons and social behavior.Frontiers in neuroscience · 2023Article
- Nutrition, nutritional deficiencies, and schizophrenia: An association worthy of constant reassessment.World journal of clinical cases · 2021Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 677C>T 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 677C>T polymorphism was carried out to assess if this association is causal. A 5 micromol/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 677C>T polymorphism provides support for causality between a disturbed homocysteine metabolism and risk of schizophrenia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.