Interferon-γ +874T/A polymorphism, Toxoplasma gondii serostatus, and risk of paranoid schizophrenia in males: a case–control study

Background and Hypothesis Toxoplasma 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 design We 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 results TG 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. Conclusions In 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.