Case-control study finds no link between Toxoplasma gondii, IFN-γ polymorphism, and paranoid schizophrenia in males

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Frontiers in Medicine Published March 30, 2026 Medically reviewed May 1, 2026 DOI ↗ By Dr. Ji-eun Park, MD · Brain, Mind & Pain

Key Takeaway

Consider these null results when evaluating TG serostatus as a potential biomarker for paranoid schizophrenia risk.

A case-control study conducted at two mental health centers in Israel examined whether Toxoplasma gondii (TG) serostatus and the IFN-γ +874T/A polymorphism genotype jointly increase risk for paranoid schizophrenia. The study included 103 adult males meeting DSM-IV criteria for paranoid schizophrenia and 102 healthy male controls. The primary outcome was case status as a function of TG serostatus, genotype, and their interaction.

Results showed the TG seropositivity rate was nearly identical in cases and controls. TG serostatus was not associated with case status, and no TG×genotype interaction was detected. The IFN-γ +874T/A polymorphism showed no evidence of contributing to disease risk. Exact numbers, effect sizes, and p-values were not reported for these null findings.

Safety and tolerability data were not reported. The study's limitations were not explicitly detailed, but the authors note these are transparent null results that refine plausible effect sizes. The practice relevance is cautious: these findings argue against overinterpreting adult TG seropositivity as a biomarker of psychosis risk. Future studies should target developmental timing and immune-functional markers before infection-related screening or prevention can be justified.

Study Details

Study typeCohort

EvidenceLevel 3

PublishedMar 2026

View Original Abstract ↓

Background and HypothesisToxoplasma gondii (TG) exposure and host immunogenetic variation have been implicated in psychosis. Interferon-gamma (IFN-γ) is central to TG control; the IFN-γ +874T/A polymorphism has been linked to variability in IFN-γ production. We hypothesized that TG seropositivity and IFN-γ +874T/A jointly increase risk for paranoid schizophrenia in males.Study designWe conducted a case–control study of adult males (103 cases meeting DSM-IV criteria for paranoid schizophrenia; 102 healthy controls) from two mental health centers in Israel. TG status was assessed serologically using automated ELFA/VIDAS assays. IFN-γ +874T/A was genotyped with Applied Biosystems TaqMan assays. Logistic regression modeled case status as a function of TG serostatus, genotype (AA/TA/TT), their interaction, and age. Hardy–Weinberg equilibrium (HWE) was tested among controls. Sensitivity analyses explored dominant, recessive, and additive genetic encodings.Study resultsTG seropositivity rates were nearly identical in cases and controls. Genotype distributions among controls conformed to HWE. In the primary model, TG serostatus was not associated with case status, and no TG×genotype interaction was detected. Findings were consistent across sensitivity analyses.ConclusionsIn this male paranoid-schizophrenia cohort, we found no evidence that TG serostatus, IFN-γ +874T/A, or their interaction contribute to disease risk. The near-identical TG+ prevalence across groups argues against large interaction effects under the exposure and measurement definitions used here. Transparent null results refine plausible effect sizes and caution against overinterpreting adult TG seropositivity as a biomarker of psychosis risk. Future studies should target developmental timing and immune-functional markers before infection-related screening or prevention can be justified.