Examining the interrelationship between the levels of neuroactive cytokines and T.gondii exposure on the risk for schizophrenia 公开

Saaber, Sadaf (2017)

Permanent URL: https://etd.library.emory.edu/concern/etds/k930bx986?locale=zh
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Abstract

Schizophrenia is a severe mental disorder that affects an individuals' everyday ability to function. While much is known about the symptoms of schizophrenia little is understood about what causes this disease. A potential route of inquiry is the possible role of infectious agents such as the parasite T. gondii. Mechanistically this parasitic infection may act through or in concert with immune factors such as cytokines. To examine this mechanism, I analyzed two cohorts: the Atlanta VA cohort that consists of 369 subjects and the Augusta Cohort of 123 subjects. Combining the cohorts (n=473), we saw that after adjusting for age, sex, race, and smoking status, the adjusted odds ratio for the association between T. gondii in the combined cohorts was 0.93 (95% CI 0.44-1.94). The adjusted odds ratio in the Augusta Cohort was 1.21 (0.21-7.00) and the Atlanta VA was 0.98 (.42-2.29). I also conducted analysis on a subgroup of our total sample that had cytokine data (n=213) and saw that after adjusting for the same factors, the odds ratio for the association between the infection and schizophrenia outcome was 1.24 (0.37-4.12). I also examined the relationship between being seropositive for T.gondii and cytokine levels. This analysis revealed that the cytokines Il-4, IFN-Gamma, IL-2, Il-1Beta and Il-6 were significantly different between infected and non-infected individuals (alpha=0.05). The finding with IL-4 and IFN-Gamma is relevant to the tryptophan/kynurenine pathway, which is regulated by these two cytokines and has been of considerable prior interest in schizophrenia.

Table of Contents

Abstract.....................................................................................Page 4

Background / Literature Review. ....................................................... Page 8

Methods....................................................................................Page 15

Results.....................................................................................Page 19

Discussion. ............................................................................... Page 27

Future Directions...........................................................................Page 31

References..................................................................................Page 33

Tables/Figures..............................................................................Page 37

Appendices..................................................................................Page 49

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