# Neuroinflammation and Oxidative Stress in Veterans with Schizophrenia

> **NIH VA IK2** · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · 2022 · —

## Abstract

This Veterans Affairs Career Development Award (CDA-2) proposes to examine levels of neuroinflammation
and oxidative stress in the brains of Veterans with schizophrenia, and to relate these processes to each other
and to important functional outcomes. Neuroinflammation, which refers to the recruitment of immune cells in
response to injury, and the antioxidant defense system (AODS), which refers to the molecules and enzymes
that neutralize an excess of free radicals (oxidative stress), are important protective responses to injury in the
brain. Both have been shown to be altered in schizophrenia compared to healthy controls, and may be related
to the pathogenesis of schizophrenia. Furthermore, their relationship to disrupted functional outcomes in
schizophrenia including occupational status, housing status, and social relationships, remains relatively
unstudied. Until recently, markers for neuroinflammation and the AODS have only been examined in
postmortem tissue, peripheral blood, or cerebrospinal fluid (CSF) of patients. This CDA-2 proposes to
examine both neuroinflammation and the AODS directly in brain of Veterans with schizophrenia and control
subjects with two relatively novel techniques: 1) neuroinflammation will be measured with second-generation
radioligand binding to the molecule translocator protein (TSPO), using positron emission tomography (PET);
subjects will be genotyped in order to exclude the low affinity binding phenotype prior to entering the study, and
2) the AODS will be measured with levels of glutathione, the most important antioxidant molecule in the brain,
using magnetic resonance spectroscopy (MRS). The specific area of focus will be dorsolateral prefrontal
cortex in light of this area’s importance for cognitive function in schizophrenia. The project has three scientific
goals: a) Brain levels of neuroinflammation and the AODS will be compared between patients with
schizophrenia and healthy controls. b) The relationship of neuroinflammation and oxidative stress to each
other in patients will be examined, along with their relationship to cognitive performance and community
function via clinical assessments and interviews. c) The peripheral inflammatory markers TNF-a, IL-6, IL-10,
INF-g and CRP will be measured, and their relationship to the above central markers will be examined. This
information will shed light on the roles of two key processes in the brain in schizophrenia, and their influence
on quality of life for Veterans with schizophrenia. In addition to these scientific aims, this proposal will provide
the applicant, Dr. Yvonne Yang, with expertise in PET neuroimaging and MRS neuroimaging, and expertise in
the field of neuroinflammation in schizophrenia. Dr. Yang’s training plan includes regular meetings with her
mentors: expert in PET neuroimaging Dr. Mark Mandelkern, MRS physicist Dr. Albert Thomas, psychiatrist and
expert in MRS of glutathione Dr. Richard Maddock, expert in psychoneuroimmunology Dr. Michael Irwi...

## Key facts

- **NIH application ID:** 10426029
- **Project number:** 5IK2CX001875-03
- **Recipient organization:** VA GREATER LOS ANGELES HEALTHCARE SYSTEM
- **Principal Investigator:** Yvonne S Yang
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426029

## Citation

> US National Institutes of Health, RePORTER application 10426029, Neuroinflammation and Oxidative Stress in Veterans with Schizophrenia (5IK2CX001875-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10426029. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*