The role of Toxoplasma gondii and Kynurenine metabolism in cognitive impairments in Schizophrenia Open Access

Gandhi,Zeal (Spring 2018)

Permanent URL: https://etd.library.emory.edu/concern/etds/g445cd164?locale=en
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Abstract

Around 85% of schizophrenic patients suffer from some form of cognitive impairment and the severity of these cognitive impairments correspond to the severity of impaired everyday functioning. The neurobiological mechanisms underlying these cognitive impairments is not well understood, impeding drug discovery efforts. Previous studies have shown an association between infection and immune dysfunction and cognitive deficits with higher levels of some cytokines corresponding to worse cognitive scores. Chronic inflammation linked to persistent infections can modulate tryptophan/ kynurenine metabolism. The aim of this study is to assess levels of various metabolites of the “Kynurenine Pathway of Tryptophan metabolism” and related biomarkers (neopterin, tyrosine and phenylalanine) in relation to cognitive deficits across domains including processing speed, working memory, verbal, and visual learning. The effect of Kynurenic Acid (KYNA) is determined by the characteristics of the specific receptors on which it acts, and we hypothesized that the relative potency of KYNA at GPR35 receptors to reduce inflammation may correspond to better cognition. Thus, KYNA may have either a deleterious or salutary effect on cognition in schizophrenia, but this has not been previously assessed. Demographic, biologic, and cognitive data from 71 patients recruited from the Atlanta Veterans Affairs Medical Center was assessed in this study. Linear regression analysis was conducted for each of the cognitive variables and immune biomarkers adjusted for covariates like age, sex, race, and smoking status. Results indicate that KYNA levels in blood were higher in controls and were significantly associated with better cognition as determined by the Letter Number Span (LNS), fluency, Brief Assessment of Cognition in Schizophrenia-Symbol Coding (BACS-SC), Trail Making Test (TMT), Wisconsin Card Sorting Test (WCST), and RIST Index. The levels of Tryptophan were significantly higher in controls and corresponded to better scores on LNS, WCST and WMS. These findings may indicate the protective effect of KYNA through the GPR35 receptor in the periphery.

 

Table of Contents

Table of Contents

 

 

Chapter 1. Literature Review and Background. 1

Chapter 2. Thesis Manuscript 7

Introduction. 7

Methods. 9

Results. 15

Discussion. 19

References. 22

Tables and Figures. 35

Chapter 3. Public Health Implications, Future Directions and Summary. 87

Appendices. 89

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