Toxoplasma gondii: Biological Parameters of the Connection to Schizophrenia

Abstract

It is increasingly evident that the brain is not truly an immune privileged site and that cells of the central nervous system are sensitive to the inflammation generated when the brain is fighting off infection. Among the many microorganisms that have access to the brain, the apicomplexan protozoan Toxoplasma gondii has been one of the most studied. This parasite has been associated with many neuropsychiatric disorders including schizophrenia. This article provides a comprehensive review of the status of Toxoplasma research in schizophrenia. Areas of interest include (1) the limitations and improvements of immune-based assays to detect these infections in humans, (2) recent discoveries concerning the schizophrenia-Toxoplasma association, (3) findings of Toxoplasma neuropathology in animal models related to schizophrenia pathogenesis, (4) interactions of Toxoplasma with the host genome, (5) gastrointestinal effects of Toxoplasma infections, and (6) therapeutic intervention of Toxoplasma infections.

Fig. 1.

Odds ratios associated with Toxoplasma exposure by clinical diagnosis. Bars represent odds ratios (Mean-95% confidence interval) associated with the indicated clinical diagnosis calculated by logistic regression as described in the text with age, gender, race, maternal education, and place of birth as covariates. The abbreviations used are as follows: Scz = nonrecent schizophrenia; Bp = nonrecent bipolar disorder; Maj Depr = major depressive disorder without recent onset psychosis; ROP-All = recent onset psychosis, all cases; ROP-Non-aff = recent onset psychosis, individuals with nonaffective psychosis; ROP-Aff = recent onset psychosis, individuals with affective psychosis. *** P < .003, **P < .03. Not recent onset refers to individuals who did not have recent onset of psychosis. Reprinted from PLoS Negl Trop Dis. 2017 Nov; 11(11): e0006040.

Fig. 2.

Underestimates of Toxoplasma seropositivity revealed by immunoblotting. We performed a pilot study of 34 individuals, 25 of whom had psychiatric disorders. Cellular lysate from Toxoplasma gondii strain RH were homogenized and subjected to sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) and Western blotting using the human sera characterized in ELISAs. A total protein stain of the cellular lysate is shown in the first lane. Standards listed in the far left of the diagram refer to kilodaltons. ELISA mod negative refers to an absorbance value that was slightly elevated from a true negative value. ELISA positive refers to an absorbance value that was slightly below the positivity cutoff value. Twelve of 34 individuals were positive for IgG via immunoblotting compared to 3 who were positive based on ELISAs.

Fig. 3.

Individual differences at the species level in chronic Toxoplasma infected and uninfected mice. Female CD-1 mice were infected intraperitoneally with 500 GT1 tachyzoite, whereas uninfected controls received PBS only (5 per group). To establish a chronic infection, both control and infected mice were treated with sulfadiazine sodium (400 mg/L) from day 5 to 30. Mice were killed at 5 months postinfection. 16S rDNA libraries were sequenced using the MiSeq Illumina sequencing platform. Sequences were analyzed utilizing QIIME 1 focusing on v3–v4 region. The graph shows the relative bacterial composition of the intestinal microflora in each mouse. Species that has higher than 100 average counts are depicted individually, lower counts are combined in the “Other” taxa.