PT  - JOURNAL ARTICLE
AU  - Yukiko Tomioka
AU  - Shusuke Numata
AU  - Makoto Kinoshita
AU  - Hidehiro Umehara
AU  - Shin-ya Watanabe
AU  - Masahito Nakataki
AU  - Yoshimi Iwayama
AU  - Tomoko Toyota
AU  - Masashi Ikeda
AU  - Hidenaga Yamamori
AU  - Shinji Shimodera
AU  - Atsushi Tajima
AU  - Ryota Hashimoto
AU  - Nakao Iwata
AU  - Takeo Yoshikawa
AU  - Tetsuro Ohmori
TI  - Decreased serum pyridoxal levels in schizophrenia: meta-analysis and Mendelian randomization analysis
AID  - 10.1503/jpn.170053
DP  - 2018 May 01
TA  - Journal of Psychiatry and Neuroscience
PG  - 194--200
VI  - 43
IP  - 3
4099  - http://jpn.ca/content/43/3/194.short
4100  - http://jpn.ca/content/43/3/194.full
SO  - J Psychiatry Neurosci2018 May 01; 43
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.