Special Issue: Does latent Toxoplasma infection mimic the immune profile of schizophrenia? Sex-specific cytokine and brain-marker alterations suggest partial overlap.

Abstract

Schizophrenia often features low-grade neuroinflammation. Because latent toxoplasmosis (LT) is more prevalent among individuals with schizophrenia, we tested whether LT yields a biomarker pattern resembling that reported in schizophrenia. We quantified 15 cytokines and 15 blood markers of brain injury in 65 LT-positive individuals and 103 matched LT-negative controls using multiplex immunoassays. Multivariate effects of infection, age, sex, and their interaction were assessed by MANCOVA and PERMANOVA. Effects on individual biomarkers were tested by partial Kendall correlation (controlling for age and sex). Differences in the internal correlation structure were evaluated with Mantel tests on dissimilarity matrices derived from partial correlations. LT was associated with higher KLK6, S100B, and TDP-43, and lower MIF; several other markers showed nonsignificant but sizable trends. Cytokines showed reduced IFN-γ, IL-1β, and MCP-1, and elevated IL-13 and IL-17 in the infected group. Sex-stratified analyses suggested stronger effects on brain-injury markers in women and on cytokines in men. Correlation structure also diverged: infected individuals exhibited more negative links between brain-injury markers and cytokines, whereas controls showed predominantly positive associations (Mantel r = 0.461, p = 0.043). The LT profile overlapped with schizophrenia in elevated KLK6 and S100B and, in men, reduced GDNF, but contrasted for MIF and for the overall cytokine pattern (no consistent IL-6/TNF-α elevation). LT entails neuroinflammatory and neuroimmune alterations that only partly recapitulate schizophrenia; the biomarker pattern and interrelationships differ, arguing against LT as the main driver of schizophrenia-related neuroinflammation.