Decreased serum pyridoxal levels in schizophrenia: meta-analysis and Mendelian randomization analysis.
J Psychiatry Neurosci
From the Department of Psychiatry, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan (Tomioka, Numata, Kinoshita, Umehara, Watanabe, Nakataki, Ohmori); the Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan (Iwayama, Toyota, Yoshikawa); the Department of Psychiatry, School of Medicine, Fujita Health University, Aichi, Japan (Ikeda, Iwata); the Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan (Yamamori, Hashimoto); the Department of Neuropsychiatry, Kochi Medical School, Kochi University, Kochi, Japan (Shimodera); the Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Ishikawa, Japan (Tajima); and the Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan (Hashimoto).
Published: May 2018
AI Article Synopsis
- The study associated alterations in one-carbon metabolism, specifically lower serum pyridoxal (a form of vitamin B6), with schizophrenia in a large Japanese cohort.
- Despite finding significantly lower pyridoxal levels in patients with schizophrenia, genetic analysis did not show a significant link between a specific SNP (rs4654748) and the disorder.
- The Mendelian randomization approach did not establish a causal relationship between pyridoxal levels and schizophrenia risk, suggesting more research is needed to understand this connection.
Article Abstract
Background: Alterations in one-carbon metabolism have been associated with schizophrenia, and vitamin B6 is one of the key components in this pathway.
Methods: We first conducted a case-control study of serum pyridoxal levels and schizophrenia in a large Japanese cohort ( = 1276). Subsequently, we conducted a meta-analysis of association studies ( = 2125). Second, we investigated whether rs4654748, which was identified in a genome-wide association study as a vitamin B6-related single nucleotide polymorphism, was genetically implicated in patients with schizophrenia in the Japanese population ( = 10 689). Finally, we assessed the effect of serum pyridoxal levels on schizophrenia risk using a Mendelian randomization (MR) approach.
Results: Serum pyridoxal levels were significantly lower in patients with schizophrenia than in controls, not only in our cohort, but also in the pooled data set of the meta-analysis of association studies (standardized mean difference -0.48, 95% confidence interval [CI] -0.57 to -0.39, = 9.8 × 10-24). We failed to find a significant association between rs4654748 and schizophrenia. Furthermore, an MR analysis failed to find a causal relationship between pyridoxal levels and schizophrenia risk (odds ratio 0.99, 95% CI 0.65-1.51, = 0.96).
Limitations: Food consumption and medications may have affected serum pyridoxal levels in our cross-sectional study. Sample size, number of instrumental variables and substantial heterogeneity among patients with schizophrenia are limitations of an MR analysis.
Conclusion: We found decreased serum pyridoxal levels in patients with schizophrenia in this observational study. However, we failed to obtain data supporting a causal relationship between pyridoxal levels and schizophrenia risk using the MR approach.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915240 | PMC |
| http://dx.doi.org/10.1503/jpn.170053 | DOI Listing |
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