Association of Folate Level in Blood with the Risk of Schizophrenia

Comb Chem High Throughput Screen. 2017;20(2):116-122. doi: 10.2174/1386207320666170117120828.


Aim and objective: The aim of this study was to evaluate the association between folate level and the risk of schizophrenia and to identify possible biomarker for schizophrenia.

Materials and methods: Data about folate were extracted from 16 high quality studies. The association of folate level in blood and schizophrenia was evaluated using standardized mean difference (SMD) and 95% confidence interval (CI).

Results: Totally 1183 (52.1%) cases and 1089 (47.9%) controls were included in the current metaanalysis. Folate level in schizophrenia patients was significantly lower than that in healthy controls (SMD= -0.65; 95% CI: [-0.86, -0.45]; P <0.00001). Subgroup analysis demonstrated that the decreased folate level was found in both Asian and European patients (SMD=-0.86, P<0.00001; SMD=-0.44, P<0.00001, respectively), while there were no significant differences in patients from other areas (P>0.05). Sensitivity analysis confirmed that these results were stable and reliable, no publication bias existed in our meta-analysis based on Egger's and Begg's tests (P=0.48 and 0.30, respectively).

Conclusion: These results suggest that decreased folate may be a risk factor for schizophrenia. More epidemiological and biochemistry studies are required to describe how folate or folate supplementation play roles in the progress of schizophrenia.

Keywords: Folate; case-control study; folic acid; meta-analysis; neurodevelopmental disorders; schizophrenia.

Publication types

  • Meta-Analysis

MeSH terms

  • Biomarkers / blood
  • Disease Susceptibility / blood
  • Disease Susceptibility / diagnosis
  • Folic Acid / blood*
  • Humans
  • Racial Groups
  • Risk Factors
  • Schizophrenia / blood*


  • Biomarkers
  • Folic Acid