Exploring Toxoplasma Gondii Seropositivity and Neuroimmune Markers Across Neuropsychiatric Disorders Restricted; Files Only

Abstract

This thesis had two primary aims. The first was to determine the seroprevalence of Toxoplasma gondii (T. gondii), a neurotropic parasite, in three neuropsychiatric cohorts: individuals with 22q11.2 deletion syndrome (22q11DS, N=72), posttraumatic stress disorder (PTSD, N=30), and opioid use disorder (OUD, N=20). The second aim focused on evaluating immune and neurophysiological associations in the 22q11DS cohort. T. gondii IgG was assayed using ELISA, while cytokines (e.g. interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha)) and BBB markers (e.g. glial fibrillary acidic protein (GFAP), matrix metalloproteinase-9 (MMP9)) were quantified using Mesoscale Discovery assays. Across all cohorts, T. gondii seropositivity was relatively low (0-12.5%) compared to expected population estimates. For the  22q11DS cohort, I also examined the levels of circulating inflammatory cytokines, IFN-gamma and TNF-alpha), along with markers of BBB disruption, to determine whether they predicted alterations in psychophysiological indices (specifically acoustic startle parameters). In linear regression analysis with pre-chosen covariates, most of the biomolecular predictors were not statistically associated with the acoustic startle parameters. However, when models were further explored using backward stepwise regression analysis, there was evidence that higher logIFN-gamma (pg/ml) was associated with longer startle latency (log ms), B=4.497 (95% CI .796, 8.790), whereas TNF-alpha showed the opposite effect, B=-7.394 (95% CI -13.806,-.982). These models were adjusted for body mass index (BMI), race, age, and the interaction term of these cytokines with BBB markers: GFAP (log fg/ml), which had a negative interaction coefficient with IFN-gamma and a positive interaction term for TNF-alpha. The model included an interaction term for MMP9 (Log pg/ml), which showed some evidence of interaction with IFN-gamma (p=0.097). Taken together, using various statistical techniques, my thesis indicates that T. gondii seropositivity is relatively low in the three neuropsychiatric cohorts examined. Moreover, among persons with 22q11DS, there may be an association between inflammatory cytokines and acoustic startle parameters. This work should be followed up with analysis using a larger sample size, additional cytokines, and blood-brain barrier markers. Further studies could use similar techniques to examine the association between these blood molecules and a variety of psychometric test scores that are available in these cohorts.

Table of Contents

Introduction ................................................................................................................................... 1

Toxoplasma gondii ...................................................................................................................................................... 1

22q11.2 deletion syndrome ................................................................................................................................... 3

Posttraumatic stress disorder (PTSD) .................................................................................................................. 5

Substance Use Disorders – Opioids: .................................................................................................................... 6

Research Context and Objectives ......................................................................................................................... 7

Methods .......................................................................................................................................... 8

Study Selection and Data Extraction ................................................................................................................... 8

a) 22q11.2DS: .......................................................................................................................................................... 8

b) PTSD: ................................................................................................................................................................... 10

c) Opioid: ................................................................................................................................................................ 10

Statistical Analysis ..................................................................................................................................................... 11

Detection of Antibodies (anti-Toxo. gondii IgG, anti-SARS-COV-2) ..................................................... 11

quantification of Antibodies cytokines and blood brain barrier markers ........................................... 12

Results ........................................................................................................................................... 13

Demographic Characteristics ............................................................................................................................... 13

T. gondii Seropositivity (amongst all three cohorts) ................................................................................... 16

Further exploration into 22q11DS ...................................................................................................................... 17

Discussion ..................................................................................................................................... 46

References .................................................................................................................................... 50

Appendix .......................................................................................................................................... i

About this Master's Thesis

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• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Global Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Biology, Molecular Health Sciences, Immunology Health Sciences, Epidemiology
Keyword	Psychiatric Illness Toxoplasma Gondii Molecular Epidemiology
Committee Chair / Thesis Advisor	Brad Pearce, Emory University

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