Scrutinizing the causal relationship between schizophrenia and vitamin supplementation: a Mendelian randomization study

Abstract Objective: Observational studies have reported malnutrition and vitamin deficiency in patients with schizophrenia (SZ), which can lead to serious metabolic syndromes and decrease anti-psychiatric drug outcomes. Whereas, vitamin intake along with psychiatric medication can enhance the medication outcomes. However, it is still unknown if SZ induces vitamin deficiency. Herein, we conduct the Mendelian randomization analysis to explore the causal relationship between schizophrenia and vitamins supplementation. Methods: We retrieved the genome-wide summary statistical data for schizophrenia from recent SZ GWAS data (43,175 cases and 65,166 controls) and vitamins supplementation GWAS data from Neale's GWAS datasets (more than 337,000 samples from the European population) and performed a two-sample Mendelian randomization analysis to determine the causal association of SZ with vitamin supplementation, in addition, we conduct the sensitivity analysis to obtain reliable results and remove confounding bias. Results: SZ have causal relationships with vitamins A, B, C, D, and E (SZ/vitamin A: β = 0.002, se = 0.001, 95% confidence interval (CI): 0.001 to 0.004, P = 1.41E-05, heterogeneity P = 0.4486; SZ/vitamin B: β = 0.004, se = 0.001, 95% CI: 0.002-0.005, P = 7.0E-05, heterogeneity P = 0.2217; SZ/vitamin C: β = 0.004, se = 0.001, 95% CI: 0.002-0.007, P = 0.001, heterogeneity P = 0.1349; SZ/vitamin D: β = 0.003, se = 0.001, 95% CI: 0.002-0.005, P = 0.001, heterogeneity P = 0.433; SZ/vitamin E: β = 0.003, se = 0.001, 95% CI: 0.002-0.005, P = 5.0E-05, heterogeneity P = 0.1382). Conclusion: Our findings suggest that vitamin levels and supplementation should be carefully controlled in patients with SZ, which in turn may enhance the therapeutic effects of antipsychotic drug treatments.