Background: Dohan first proposed that there may be an association between gluten sensitivity and schizophrenia in the 1950s. Since then, this association has been measured using several different serum biomarkers of gluten sensitivity. At this point, it is unclear which serum biomarkers of gluten sensitivity are elevated in patients with schizophrenia. However, evidence suggests that the immune response in this group is different from the immune response to gluten found in patients with Celiac disease.

Methods: A systematic literature review was performed to identify all original articles that measured biomarkers of gluten sensitivity in patients with schizophrenia and non-affective psychoses compared to a control group. Three databases were used: Ovid MEDLINE, Psych INFO, and Embase, dating back to 1946. Forward tracking and backward tracking were undertaken on retrieved papers. A meta-analysis was performed of specific biomarkers and reported according to MOOSE guidelines.

Results: 17 relevant original articles were identified, and 12 met criteria for the meta-analysis. Five biomarkers of gluten sensitivity were found to be significantly elevated in patients with non-affective psychoses compared to controls. The pooled odds ratio and 95% confidence intervals were Anti-Gliadin IgG OR=2.31 [1.16, 4.58], Anti-Gliadin IgA OR=2.57 [1.13, 5.82], Anti-TTG2 IgA OR=5.86 [2.88, 11.95], Anti-Gliadin (unspecified isotype) OR=7.68 [2.07, 28.42], and Anti-Wheat OR=2.74 [1.06, 7.08]. Four biomarkers for gluten sensitivity, Anti-EMA IgA, Anti-TTG2 IgG, Anti-DGP IgG, and Anti-Gluten were not found to be associated with schizophrenia.

Conclusions: Not all serum biomarkers of gluten sensitivity are elevated in patients with schizophrenia. However, the specific immune response to gluten in this population differs from that found in patients with Celiac disease.