Decreased serum pyridoxal levels in schizophrenia: Meta-analysis and Mendelian randomization analysis

Yukiko Tomioka, Shusuke Numata, Makoto Kinoshita, Hidehiro Umehara, Shin ya Watanabe, Masahito Nakataki, Yoshimi Iwayama, Tomoko Toyota, Masashi Ikeda, Hidenaga Yamamori, Shinji Shimodera, Atsushi Tajima, Ryota Hashimoto, Nakao Iwata, Takeo Yoshikawa, Tetsuro Ohmori

研究成果: Article

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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 (n = 1276). Subsequently, we conducted a meta-analysis of association studies (n = 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 (n = 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, p = 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, p = 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.

元の言語English
ページ(範囲)194-200
ページ数7
ジャーナルJournal of Psychiatry and Neuroscience
43
発行部数3
DOI
出版物ステータスPublished - 05-2018

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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    Tomioka, Y., Numata, S., Kinoshita, M., Umehara, H., Watanabe, S. Y., Nakataki, M., Iwayama, Y., Toyota, T., Ikeda, M., Yamamori, H., Shimodera, S., Tajima, A., Hashimoto, R., Iwata, N., Yoshikawa, T., & Ohmori, T. (2018). Decreased serum pyridoxal levels in schizophrenia: Meta-analysis and Mendelian randomization analysis. Journal of Psychiatry and Neuroscience, 43(3), 194-200. https://doi.org/10.1503/jpn.170053