# Schizophrenia and autoimmune disorders: the role of microglial cells

> **NIH NIH P20** · UNIVERSITY OF NEVADA LAS VEGAS · 2022 · $399,485

## Abstract

ABSTRACT: RESEARCH PROJECT 3  
 Schizophrenia (SCZ) is a complex psychiatric disorder that presents unique challenges in the study of 
disease biology. There are no objective biological phenotypes and the etiology is unknown. These lead to 
tremendous difficulty in diagnosis and treatments. The study of neurobiology underlying this severe psychiatric 
disorder has been hindered by the lack of access to the tissue of interest – neurons or other cells like microglia 
(the resident immune cells) from patients' brain. In recent years, several lines of studies have found that SCZ 
has high co-occurrence with autoimmune disorders (AIDs). Lately, evidence has also highlighted that microglial 
activation contributes to the risk of SCZ. Several hypotheses have been proposed regarding these studies. 
One hypothesis is that common genetic alterations or biological pathways are involved in the pathogenesis of 
both SCZ and AIDs. Another is the microglial activation hypothesis that pro-inflammatory cytokines such as IL- 
1β, IL-6 and TNF-α, produced by chronically activated microglia in the brain, are the fundamental mediators for 
SCZ. However, genetic overlap between SCZ and AIDs at a genome-wide level is largely unknown due to both 
complex disorders have a complex genetic architecture. In addition, no studies have tested directly in microglia 
derived from living patients, and the mechanism of microglial activation in the process of SCZ remains unclear. 
In this application, we hypothesize that common genetic risk factors contribute to a high incidence between 
SCZ and AIDs, and that microglial activation is a key step in the development of SCZ. Two specific aims are 
proposed in this study. In Aim 1, we will identify the shared genetic risk factors between SCZ and AIDs using 
meta-analysis and polygenic analysis. Potential shared pathways between these disorders are also examined. 
In Aim 2, we will investigate whether the microglial activation enhance the risk of SCZ. We will first establish 
induced microglia-like cells (iMGCs) from blood monocytes. We will then characterize and validate our iMGC 
model by morphology and functional study. Finally we will apply the iMGC model to investigate the role of 
microglia in the development of SCZ. To our knowledge, we will be the first to investigate the common genetic 
risk factors/pathways between SCZ and AIDs. We will also be the first to investigate the functions of microglia 
that are directly induced from blood monocytes of SCZ patients. These studies will allow us to pinpoint if, and 
to what extent, the immune system, including the AIDs risk genes and microglial activation, involve in the 
development of SCZ. Overall, our proposal has a potential to identify the immune-related risk factors in the 
etiology of SCZ, which may in turn lead to the discovery of reliable biomarkers and new therapeutic strategies 
for the care of SCZ patients. This grant will also pave a way for my career development. As I acc...

## Key facts

- **NIH application ID:** 10458482
- **Project number:** 5P20GM121325-05
- **Recipient organization:** UNIVERSITY OF NEVADA LAS VEGAS
- **Principal Investigator:** Jingchun Chen
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $399,485
- **Award type:** 5
- **Project period:** 2018-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458482

## Citation

> US National Institutes of Health, RePORTER application 10458482, Schizophrenia and autoimmune disorders: the role of microglial cells (5P20GM121325-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10458482. Licensed CC0.

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