Association between Toxoplasma gondii IgG seropositivity and schizophrenia: A case-control study in Colombia

Whether Toxoplasma gondii contributes to schizophrenia remains debated. We evaluated this association using a matched case-control design with two comparison groups and examined serotype distribution and clinical/cognitive correlates. We included 100 schizophrenia cases, 97 genetic controls (biological relatives up to third degree), and 100 environmental controls (age- and neighborhood-matched). Anti-T. gondii IgG/IgM were measured using an enzyme-linked fluorescence assay; among IgG-positive participants, serotyping was performed with GRA6-based ELISA. Associations were estimated using unadjusted odds ratios, Mantel-Haenszel common odds ratios, and conditional logistic regression by matched sets. Symptoms, functioning, and MATRICS cognitive performance were compared by serostatus among cases. Serology was available for 292 participants. IgG seropositivity was lower in cases than in genetic and environmental controls (20.2% vs 45.7% and 31.3% respectively). The unadjusted odds ratio for schizophrenia was 0.41 (95% CI 0.23-0.72), and the Mantel-Haenszel estimate was 0.32 (95% CI 0.17-0.62). In conditional models, the inverse association persisted for the case-environmental contrast after adjustment (aOR 0.32, 95% CI 0.07-1.51), whereas the case-genetic contrast was non-estimable due to quasi-complete separation. Serotyping showed predominance of GRA6-III without group differences. Among cases, symptoms, functioning, and MATRICS performance did not differ by serostatus, and leave-one-stratum-out analyses supported stable directionality. In this Colombian sample, findings do not support a positive association between T. gondii exposure and schizophrenia. Regional factors such as strain diversity, exposure timing, and host/environmental characteristics may modify risk. Prospective studies incorporating molecular genotyping and temporal measures of exposure are warranted.