Chronic Toxoplasma gondii Seropositivity and Its Association with Major Depressive Disorder and Mild Cognitive Impairment: A Case–Control Study of Inflammatory and Kynurenine Pathway Biomarkers

Abstract

Background: Chronic Toxoplasma gondii (TG) infection has been implicated in neuropsychiatric disorders through immune activation and kynurenine pathway dysregulation. Objectives: To investigate the association between chronic TG seropositivity and major depressive disorder (MDD) and mild cognitive impairment (MCI), and to assess the mediating role of inflammatory biomarkers and the kynurenine/tryptophan (Kyn/Trp) ratio. Materials and Methods: Two unmatched case–control studies were conducted in Baghdad. TG IgG/IgM measured by ELISA; IgG avidity defined chronic infection. IL-6, TNF-α, hs-CRP quantified by ELISA; Kyn/Trp measured by HPLC. Multivariable logistic regression and mediation analyses were performed. Results: TG seropositivity was significantly higher in MDD and MCI cases. Elevated inflammatory markers and Kyn/Trp ratio partially mediated these associations. Conclusion: Chronic TG infection is associated with increased odds of MDD and MCI, partly through immune-inflammatory and kynurenine pathway mechanisms.