Investigating the Impact of Inflammation on Brain Reward Regions using Diffusion Tensor Imaging and their Relationship to Negative Symptoms in Patients with Schizophrenia Open Access

Abstract

This thesis aims to better understand brain-immune interactions using diffusion tensor imaging (DTI) to determine if structural changes in the brain are related to negative symptoms of schizophrenia. Negative symptoms, including motivational deficits, are some of the most debilitating aspects of schizophrenia, being both treatment resistant and impede functional recovery. One potential mechanism that may contribute to negative symptoms and motivational deficits is inflammation. Specifically, this thesis looks at the effect of inflammation on the regions of interest (ROI) of the ventral striatum (VS) and the ventromedial prefrontal cortex (vmPFC). Both these areas of interest have been shown in previous work by the lead mentor, Dr. David Goldsmith, as well as other teams, in transdiagnostic work in depression, to be involved in inflammation’s effect on anhedonia and negative symptoms. DTI is a neuroimaging technique used to study structural brain changes by determining water movement on a microscopic level, measuring fractional anisotropy (FA) and mean diffusivity (MD). The underlying hypothesis of this thesis is that inflammatory markers will be associated with changes in brain structure of the ROI using DTI which will be associated with negative symptom burden in patients with schizophrenia. To asses this hypothesis, 39 patients with schizophrenia or schizoaffective disorder, ages of 18 to 45, who had been recruited at the outpatient Grady Behavioral Health Clinic were analyzed. Baseline hsCRP and other markers of inflammation were gathered, as well as DTI scans for each patient. Here we show in the subset of individuals with high inflammation (hsCRP>2), an association between VS MD and increased inflammation (measured by hsCRP) as well as an association between vmPFC FA and increased inflammation (measured by hsCRP). The results from the data did not broadly demonstrate an association between inflammation and the DTI measures MD and FA for the ROI otherwise. Nor did it show a statistically significant association between the FA MD values for the ROI and negative symptoms. The results from this thesis showed mixed results. Further studies using longitudinal study design and anti-inflammatory challenges may yield more conclusive evidence. 

  

Table of Contents

 

1.    Introduction

5.  Specific Aims

9.  Methods

13. Figure 1

16. Results

16. Table 1

17. Table 2

18. Table 3

18. Table 4

19. Table 5

20. Table 6

20. Table 7

21. Discussion

24. Conclusion

 

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Mental Health
Keyword	Schizophrenia Psychiatry DTI
Committee Chair / Thesis Advisor	Dr. Amita Manatunga, Emory University
Committee Members	Dr. David Goldsmith, Emory University Dr. Robert Cotes, Emory University Dr. Jordan Kempker, Emory University

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