ArticleSchizophrenia bulletin2013
Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia.
Article in Schizophrenia bulletin, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Integrative analysis of genome-wide association studies identifies novel loci associated with neuropsychiatric disorders.Translational psychiatry · 2021Pooled it
- Meta-analyses of blood homocysteine levels for gender and genetic association studies of the MTHFR C677T polymorphism in schizophrenia.Schizophrenia bulletin · 2014Pooled it
- Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial.Molecular psychiatry · 2018Trial
- Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia.JAMA psychiatry · 2013Trial
- Folate Receptor Alpha (FRα) and the Developing Brain: From Molecular Function to Neurodevelopmental Outcomes.Molecular neurobiology · 2026Review
- Case report: Rare variants in theFrontiers in psychiatry · 2024Article
- Biomarkers for Psychosis: Are We There Yet? Umbrella Review of 1478 Biomarkers.Schizophrenia bulletin open · 2024Article
- Abnormalities in one-carbon metabolism in young patients with psychosis.Frontiers in psychiatry · 2023Article
- Associations of Genetic Variants of Methylenetetrahydrofolate Reductase and Serum Folate Levels with Metabolic Parameters in Patients with Schizophrenia.International journal of environmental research and public health · 2021Article
- Early-Onset Schizophrenia: A Special Phenotype of the Disease Characterized by Increased MTHFR Polymorphisms and Aggravating Symptoms.Neuropsychiatric disease and treatment · 2021Article
- Methylenetetrahydrofolate reductase and psychiatric diseases.Translational psychiatry · 2018Review
- Prenatal one-carbon metabolism dysregulation programs schizophrenia-like deficits.Molecular psychiatry · 2018Article
- A Cross-Sectional Study of Dietary and Genetic Predictors of Blood Folate Levels in Healthy Young Adults.Nutrients · 2017Article
- Current and emergent treatments for symptoms and neurocognitive impairment in schizophrenia.Current treatment options in psychiatry · 2015Article
- Effects of second-generation antipsychotics on selected markers of one-carbon metabolism and metabolic syndrome components in first-episode schizophrenia patients.European journal of clinical pharmacology · 2014Observational
- Nutritional interventions for the adjunctive treatment of schizophrenia: a brief review.Nutrition journal · 2014Review
- Placebo analgesia and reward processing: integrating genetics, personality, and intrinsic brain activity.Human brain mapping · 2014Article
- Elevated homocysteine level in first-episode schizophrenia patients--the relevance of family history of schizophrenia and lifetime diagnosis of cannabis abuse.Metabolic brain disease · 2014Article
- The epigenome and postnatal environmental influences in psychotic disorders.Social psychiatry and psychiatric epidemiology · 2014Review
- Dopamine genetic risk score predicts depressive symptoms in healthy adults and adults with depression.PloS one · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Low serum folate levels previously have been associated with negative symptom risk in schizophrenia, as has the hypofunctional 677C>T variant of the MTHFR gene. This study examined whether other missense polymorphisms in folate-regulating enzymes, in concert with MTHFR, influence negative symptoms in schizophrenia, and whether total risk allele load interacts with serum folate status to further stratify negative symptom risk. Medicated outpatients with schizophrenia (n = 219), all of European origin and some included in a previous report, were rated with the Positive and Negative Syndrome Scale. A subset of 82 patients also underwent nonfasting serum folate testing. Patients were genotyped for the MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), MTR 2756A>G (rs1805087), MTRR 203A>G (rs1801394), FOLH1 484T>C (rs202676), RFC 80A>G (rs1051266), and COMT 675G>A (rs4680) polymorphisms. All genotypes were entered into a linear regression model to determine significant predictors of negative symptoms, and risk scores were calculated based on total risk allele dose. Four variants, MTHFR 677T, MTR 2756A, FOLH1 484C, and COMT 675A, emerged as significant independent predictors of negative symptom severity, accounting for significantly greater variance in negative symptoms than MTHFR 677C>T alone. Total allele dose across the 4 variants predicted negative symptom severity only among patients with low folate levels. These findings indicate that multiple genetic variants within the folate metabolic pathway contribute to negative symptoms of schizophrenia. A relationship between folate level and negative symptom severity among patients with greater genetic vulnerability is biologically plausible and suggests the utility of folate supplementation in these patients.
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Registered trials
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