# Peripheral and central nervous system inflammation associated with military sexual trauma and PTSD

> **NIH VA IK2** · VA SAN DIEGO HEALTHCARE SYSTEM · 2024 · —

## Abstract

Military sexual trauma (MST) is unfortunately common in Veterans, particularly in women, and has life-
long consequences for physical and mental health. MST, which includes both sexual assault and harassment,
is strongly associated with post-traumatic stress disorder (PTSD) and co-morbid conditions including,
depression, anxiety, substance use, obesity and eating disorders, chronic pain, and autoimmunity. While other
psychiatric conditions, including depression and anxiety, are associated with inflammation, PTSD is uniquely
associated with a >50% increase in autoimmune disorder prevalence (e.g., rheumatoid arthritis, thyroiditis, and
inflammatory bowel disease). Exposure to MST further increases the risk of developing an autoimmune
disorder by over two-fold. Although increased peripheral inflammation is well characterized in PTSD, it is
unclear if peripheral inflammation reflects a disruption in immune signaling in the central nervous system
(CNS). Moreover, phenotyping the immune dysregulation that occurs with PTSD has almost exclusively
occurred through cross-sectional data collection. However, without longitudinal studies that track immune
biomarkers in conjunction with symptoms, it is unknown if immune biomarkers have clinical utility in guiding
treatment. Furthermore, while epidemiological data support that trauma disorders, particularly MST, may have
shared risk factors with autoimmune disorders, it is unknown if MST confers unique effects on immune
signaling. Filling these gaps is critical to understanding if and how immune dysregulation contributes to
symptom "state" in Veterans with MST to inform its viability as a potential mechanism for targeted treatment.
 This proposal will address these knowledge gaps by quantifying circulating inflammatory cytokines in
Veterans with MST-related PTSD (+MST/+PTSD) and comparing cytokine levels to Veterans without PTSD or
MST. In addition to examining circulating plasma cytokines, we will also measure cytokines and miRNA
isolated from and astrocyte-derived exosomes (ADEs), which are extracellular vesicles that carry RNA and
protein cargo to the blood from the CNS. Measuring biomarkers from exosome populations derived from CNS-
tissue sources can non-invasively assess neuroinflammation and compare peripheral vs. central inflammation
links to PTSD symptoms. We hypothesize that levels of baseline peripheral (plasma) and central (exosome)
inflammatory markers will be altered in female Veterans with +MST/+PTSD compared to female Veterans
without MST or PTSD. Based on the existing literature of psychoneuroimmunologic correlates of PTSD, we will
quantify IL-1β, IL-2, IL-6, IFNγ, and TNFα cytokines from both plasma and exosome cargo using multiplex
arrays. We will also quantify immune regulatory miRNA from exosome cargo. In the +MST/+PTSD group, we
will also collect plasma samples at 3- and 6-month follow-up visits to determine if inflammatory biomarkers are
associated with symptom trajectory across time. A h...

## Key facts

- **NIH application ID:** 10909796
- **Project number:** 5IK2CX002343-03
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Victoria B Risbrough
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909796

## Citation

> US National Institutes of Health, RePORTER application 10909796, Peripheral and central nervous system inflammation associated with military sexual trauma and PTSD (5IK2CX002343-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10909796. Licensed CC0.

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