# Imaging Microglial Activation in PTSD with PET

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $753,301

## Abstract

Project Summary
Nearly 9 in 10 Americans will be exposed to trauma in their lifetime and 1 in 10 will develop post-traumatic
stress disorder (PTSD), which is characterized by elevated threat (e.g., intrusions, anxious arousal), loss (e.g.,
anhedonia, negative affect) and neurocognitive (e.g., verbal learning, attention) symptoms. Individuals with
PTSD have elevated rates of physical health conditions, as well as functional impairment, with loss symptoms
in particular contributing to decreased quality of life. The immune system is responsible for maintaining health,
which includes mounting a response to physical (e.g., virus, injury) and psychological (e.g., stress) insults, as
well as modulating the progression of neurodegenerative disorders such as Alzheimer’s disease. All of these -
physical health conditions, psychological distress, and neurodegenerative disorders - are more prevalent in
individuals with than without PTSD. There are peripheral immune system abnormalities in PTSD; however, no
known study has evaluated the role of the neuroimmune system in PTSD. In the healthy immune system, the
response of the central nervous system to an insult or damage is mediated by the activation of microglia, which
carry out repair functions. However, excessive activation can lead to neuronal dysfunction and damage
through the release of inflammatory cytokines and stress hormones, and may contribute to neurodegeneration,
such as that found in individuals with PTSD. When microglia are activated, there is a robust increase in the
expression of translocator protein (TSPO). Positron emission tomography (PET) radiotracers such as
[11C]PBR28, which bind to TSPO, can therefore be used to measure levels of activated microglia in vivo. In
addition to measuring levels of activated microglia in individuals with PTSD (vs. controls), we can also
challenge the immune system by administering E. Coli lipopolysaccharide (LPS), a potent immune activator
and measure increases in activated microglia within subject. We have recently demonstrated robust LPS-
induced increases in activated microglia, and concomitant increases in peripheral inflammatory cytokines, and
associated mood, anxiety, and neurocognitive symptoms in humans. In the proposed study, we will
systematically evaluate the relationship between “neuroinflammation”, as assessed with [11C]PBR28 and PET,
and the expression of threat, loss, and neurocognitive symptoms in 80 trauma-exposed individuals presenting
with the full dimensional spectrum of PTSD symptoms. Specifically, we will (1) determine whether individuals
with PTSD have higher levels of activated microglia compared to trauma-exposed controls; (2) use a novel
neuroimmune “stress test” to determine whether individuals with PTSD have a dysfunctional neuroimmune
response to systemic administration of LPS; and (3) determine the role of activated microglia in mediating the
relationship between peripheral inflammatory markers (e.g., TNF-α), and trauma-related s...

## Key facts

- **NIH application ID:** 10004712
- **Project number:** 5R01MH110674-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Kelly P. Cosgrove
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $753,301
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004712

## Citation

> US National Institutes of Health, RePORTER application 10004712, Imaging Microglial Activation in PTSD with PET (5R01MH110674-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10004712. Licensed CC0.

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