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

Research output: Contribution to journalArticle

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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 (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.

Original languageEnglish
Pages (from-to)194-200
Number of pages7
JournalJournal of Psychiatry and Neuroscience
Volume43
Issue number3
DOIs
Publication statusPublished - 05-2018

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Mendelian Randomization Analysis
Pyridoxal
Meta-Analysis
Schizophrenia
Serum
Vitamin B 6
Random Allocation
Odds Ratio
Confidence Intervals
Genome-Wide Association Study
Sample Size

All Science Journal Classification (ASJC) codes

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

Cite this

Tomioka, Y., Numata, S., Kinoshita, M., Umehara, H., Watanabe, S. Y., Nakataki, M., ... 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
Tomioka, Yukiko ; Numata, Shusuke ; Kinoshita, Makoto ; Umehara, Hidehiro ; Watanabe, Shin ya ; Nakataki, Masahito ; Iwayama, Yoshimi ; Toyota, Tomoko ; Ikeda, Masashi ; Yamamori, Hidenaga ; Shimodera, Shinji ; Tajima, Atsushi ; Hashimoto, Ryota ; Iwata, Nakao ; Yoshikawa, Takeo ; Ohmori, Tetsuro. / Decreased serum pyridoxal levels in schizophrenia : Meta-analysis and Mendelian randomization analysis. In: Journal of Psychiatry and Neuroscience. 2018 ; Vol. 43, No. 3. pp. 194-200.
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title = "Decreased serum pyridoxal levels in schizophrenia: Meta-analysis and Mendelian randomization analysis",
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 (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.",
author = "Yukiko Tomioka and Shusuke Numata and Makoto Kinoshita and Hidehiro Umehara and Watanabe, {Shin ya} and Masahito Nakataki and Yoshimi Iwayama and Tomoko Toyota and Masashi Ikeda and Hidenaga Yamamori and Shinji Shimodera and Atsushi Tajima and Ryota Hashimoto and Nakao Iwata and Takeo Yoshikawa and Tetsuro Ohmori",
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Tomioka, Y, Numata, S, Kinoshita, M, Umehara, H, Watanabe, SY, 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, vol. 43, no. 3, pp. 194-200. https://doi.org/10.1503/jpn.170053

Decreased serum pyridoxal levels in schizophrenia : Meta-analysis and Mendelian randomization analysis. / Tomioka, Yukiko; Numata, Shusuke; Kinoshita, Makoto; Umehara, Hidehiro; Watanabe, Shin ya; Nakataki, Masahito; Iwayama, Yoshimi; Toyota, Tomoko; Ikeda, Masashi; Yamamori, Hidenaga; Shimodera, Shinji; Tajima, Atsushi; Hashimoto, Ryota; Iwata, Nakao; Yoshikawa, Takeo; Ohmori, Tetsuro.

In: Journal of Psychiatry and Neuroscience, Vol. 43, No. 3, 05.2018, p. 194-200.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Decreased serum pyridoxal levels in schizophrenia

T2 - Meta-analysis and Mendelian randomization analysis

AU - Tomioka, Yukiko

AU - Numata, Shusuke

AU - Kinoshita, Makoto

AU - Umehara, Hidehiro

AU - Watanabe, Shin ya

AU - Nakataki, Masahito

AU - Iwayama, Yoshimi

AU - Toyota, Tomoko

AU - Ikeda, Masashi

AU - Yamamori, Hidenaga

AU - Shimodera, Shinji

AU - Tajima, Atsushi

AU - Hashimoto, Ryota

AU - Iwata, Nakao

AU - Yoshikawa, Takeo

AU - Ohmori, Tetsuro

PY - 2018/5

Y1 - 2018/5

N2 - 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.

AB - 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.

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U2 - 10.1503/jpn.170053

DO - 10.1503/jpn.170053

M3 - Article

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EP - 200

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