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Examining the Relationship between Toxoplasma gondii and Seropositivity and Serointensity and Depression in Adults from the United Kingdom and the United States: A Cross-Sectional Study.

ABSTRACT: Infecting approximately one-third of the world's population, the neurotropic protozoan Toxoplasma gondii has been associated with cognition and several neuropsychiatric diseases including schizophrenia and bipolar disorder. Findings have been mixed, however, about the relationship between Toxoplasma gondii and depression, with some studies reporting positive associations and others finding no associations. To further investigate the association between Toxoplasma gondii and depression, we used data from the UK Biobank and the National Health and Examination Survey (NHANES). Results from adjusted multiple-regression modeling showed no significant associations between Toxoplasma gondii and depression in either the UK Biobank or NHANES datasets. Further, we found no significant interactions between Toxoplasma gondii and age, sex, educational attainment, and income in either dataset that affected the association between Toxoplasma gondii and depression. These results from two community-based datasets suggest that in these samples, Toxoplasma gondii is not associated with depression. Differences between our findings and other findings showing an association between Toxoplasma gondii and depression could be due to several factors including differences in socioeconomic variables, differences in Toxoplasma gondii strain, and use of different covariates in statistical modeling.

SUBMITTER: Gale SD

PROVIDER: S-EPMC8470860 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Toxoplasma gondii (TOXO) is a neuroinvasive protozoan parasite that induces the formation of persistent cysts in mammalian brains. It infects approximately 1.1million people in the United States annually. Latent TOXO infection is implicated in the etiology of psychiatric disorders, especially schizophrenia (SCZ), and has been correlated with modestly impaired cognition. The acoustic startle response (ASR) is a reflex seen in all mammals. It is mediated by a simple subcortical circuit, and provides an indicator of neural function. We previously reported the association of TOXO with slowed acoustic startle latency, an index of neural processing speed, in a sample of schizophrenia and healthy control subjects. The alterations in neurobiology with TOXO latent infection may not be specific to schizophrenia. Therefore we examined TOXO in relation to acoustic startle in an urban, predominately African American, population with mixed psychiatric diagnoses, and healthy controls. Physiological and diagnostic data along with blood samples were collected from 364 outpatients treated at an inner-city hospital. TOXO status was determined with an ELISA assay for TOXO-specific IgG. A discrete titer was calculated based on standard cut-points as an indicator of seropositivity, and the TOXO-specific IgG concentration served as serointensity. A series of linear regression models were used to assess the association of TOXO seropositivity and serointensity with ASR magnitude and latency in models adjusting for demographics and psychiatric diagnoses (PTSD, major depression, schizophrenia, psychosis, substance abuse). ASR magnitude was 11.5% higher in TOXO seropositive subjects compared to seronegative individuals (p=0.01). This effect was more pronounced in models with TOXO serointensity that adjusted for sociodemographic covariates (F=7.41, p=0.0068; F=10.05, p=0.0017), and remained significant when psychiatric diagnoses were stepped into the models. TOXO showed no association with startle latency (t=0.49, p=0.63) in an unadjusted model, nor was TOXO associated with latency in models that included demographic factors. After stepping in individual psychiatric disorders, we found a significant association of latency with a diagnosis of PTSD (F=5.15, p=0.024), but no other psychiatric diagnoses, such that subjects with PTSD had longer startle latency. The mechanism by which TOXO infection is associated with high startle magnitude is not known, but possible mechanisms include TOXO cyst burden in the brain, parasite recrudescence, or molecular mimicry of a host epitope by TOXO. Future studies will focus on the neurobiology underlying the effects of latent TOXO infection as a potential inroad to the development of novel treatment targets for psychiatric disease.

Project description:ImportanceThe parasite Toxoplasma gondii has been associated with behavioral alterations and psychiatric disorders. Studies investigating neurocognition in people with T gondii infection have reported varying results. To systematically analyze these findings, a meta-analysis evaluating cognitive function in healthy people with and without T gondii seropositivity is needed.ObjectiveTo assess whether and to what extent T gondii seropositivity is associated with cognitive function in otherwise healthy people.Data sourcesA systematic search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. A systematic search of PubMed, MEDLINE, Web of Science, PsycInfo, and Embase was performed to identify studies from database inception to June 7, 2019, that analyzed cognitive function among healthy participants with available data on T gondii seropositivity. Search terms included toxoplasmosis, neurotoxoplasmosis, Toxoplasma gondii, cognition disorder, neuropsychological, and psychomotor performance.Study selectionStudies that performed cognitive assessment and analyzed T gondii seroprevalence among otherwise healthy participants were included.Data extraction and synthesisTwo researchers independently extracted data from published articles; if needed, authors were contacted to provide additional data. Quantitative syntheses were performed in predefined cognitive domains when 4 independent data sets per domain were available. Study quality, heterogeneity, and publication bias were assessed.Main outcomes and measuresPerformance on neuropsychological tests measuring cognitive function.ResultsThe systematic search yielded 1954 records. After removal of 533 duplicates, an additional 1363 records were excluded based on a review of titles and abstracts. A total of 58 full-text articles were assessed for eligibility (including reference list screening); 45 articles were excluded because they lacked important data or did not meet study inclusion or reference list criteria. The remaining 13 studies comprising 13 289 healthy participants (mean [SD] age, 46.7 [16.0] years; 6586 men [49.6%]) with and without T gondii seropositivity were included in the meta-analysis. Participants without T gondii seropositivity had favorable functioning in 4 cognitive domains: processing speed (standardized mean difference [SMD], 0.12; 95% CI, 0.05-0.19; P = .001), working memory (SMD, 0.16; 95% CI, 0.06-0.26; P = .002), short-term verbal memory (SMD, 0.18; 95% CI, 0.09-0.27; P < .001), and executive functioning (SMD, 0.15; 95% CI, 0.01-0.28; P = .03). A meta-regression analysis found a significant association between older age and executive functioning (Q = 6.17; P = .01). Little suggestion of publication bias was detected.Conclusions and relevanceThe study's findings suggested that T gondii seropositivity was associated with mild cognitive impairment in several cognitive domains. Although effect sizes were small, given the ubiquitous prevalence of this infection globally, the association with cognitive impairment could imply a considerable adverse effect at the population level. Further research is warranted to investigate the underlying mechanisms of this association.

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Examining the Relationship between Toxoplasma gondii and Seropositivity and Serointensity and Depression in Adults from the United Kingdom and the United States: A Cross-Sectional Study.

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