Toxoplasmosis and Schizophrenia: A Systematic Review and Meta-Analysis of Prevalence and Associations and Future Directions

Despina G Contopoulos-Ioannidis; Maria Gianniki; Angeline Ai-Nhi Truong; Jose G Montoya

doi:10.1176/appi.prcp.20210041

Toxoplasmosis and Schizophrenia: A Systematic Review and Meta-Analysis of Prevalence and Associations and Future Directions

Psychiatr Res Clin Pract. 2022 Apr 22;4(2):48-60. doi: 10.1176/appi.prcp.20210041. eCollection 2022 Summer.

Authors

Despina G Contopoulos-Ioannidis¹, Maria Gianniki², Angeline Ai-Nhi Truong³, Jose G Montoya⁴

Affiliations

¹ Department of Pediatrics, Division of Infectious Diseases, Stanford University School of Medicine Stanford California USA.
² Department of Pediatrics, University Hospital Athens Greece.
³ Stanford Prevention Research Center, Stanford University School of Medicine Stanford California USA.
⁴ Dr. Jack S. Remington Laboratory for Specialty Diagnostics, National Reference Center for the Study and Diagnosis of Toxoplasmosis Palo Alto Medical Foundation Palo Alto California USA.

Abstract

Background: A potential link between toxoplasmosis with schizophrenia (SCZ) has been extensively studied over the past 2 decades. Our study was aimed to determine whether, beyond an association, the field is primed for randomized clinical trials of anti-Toxoplasma prophylaxis in Toxoplasma seropositive patients with SCZ.

Methods: We performed a methodological appraisal of toxoplasmosis-SCZ association studies, a meta-analysis, and a compilation of claims and pathophysiologic hypotheses.

Results: We analyzed 66 studies with 11,540 patients with SCZ and 69,491 controls. For patients with SCZ, 54 studies targeted Toxoplasma-IgG seropositivity, 18 targeted Toxoplasma-IgG serointensity, and 17 targeted Toxoplasma-IgM seropositivity. For SCZ-phenotypes, 26 targeted Toxoplasma-IgG seropositivity, six targeted Toxoplasma-IgG serointensity, and three targeted Toxoplasma-IgM seropositivity. Two-thirds of these studies reported a positive association. Statistically significant associations with SCZ were reported in 31/54 studies, 11/18 studies, and 3/17 studies. Significant associations with SCZ-phenotypes were reported in 20/26 studies, 2/6 studies, and 0/3 studies, respectively. Toxoplasma-IgG seropositivity increased the odds of SCZ (OR = 1.91; 95% CI: 1.61-2.27). Heterogeneity across studies was large (I ² = 80.03%). Adjusted analyses for at least age and socioeconomic status/place of residence were done in 17 studies; temporality was addressed only in 4.

Conclusion: A large number of observational studies revealed a modest to large association between toxoplasmosis and SCZ. Although important methodological biases were identified, further association studies are unlikely to change this association and are not justified. It is time to test this association in randomized double-blind placebo-controlled clinical trials of first line anti-Toxoplasma prophylaxis in Toxoplasma seropositive patients with SCZ.