# Study of early brain alterations that predict development of chronic PTSD

> **NIH NIH R01** · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · 2020 · $658,730

## Abstract

Millions of Americans survive traumatic events (1). Symptom trajectories over the initial year 
after trauma can lead to development of chronic post-traumatic stress disorder (PTSD) or to a 
recovery free of PTSD (2-16). Neuroimaging studies indicate chronic PTSD symptoms are associated 
with changes in brain function and structure (17-32); consequently, recognition of early 
post-trauma brain changes provides an opportunity to predict chronic PTSD (33-35). Identification 
of brain changes that underlie post-trauma symptom progressions will also provide insight into 
mechanisms that distinguish PTSD development from PTSD free recovery (27, 36- 38). Surprisingly, 
progressive brain changes early after trauma have rarely been studied in trauma survivors who 
subsequently develop PTSD (33, 34). Recent results from the PI’s R21 grant provide indications of 
both early and progressive brain differences in trauma survivors who were subsequently diagnosed 
with PTSD at 3 months as compared to non-PTSD survivors. These differences include smaller volumes 
of left hippocampus (HC) and rostral anterior cingulate cortex (rACC) and greater prefrontal cortex 
(PFC) activation to an fMRI emotion appraisal task within 10 days after trauma. Furthermore, in 
survivors who developed PTSD at 3 months, progressive decreases in PFC structure and fear appraisal 
activation and increases in emotional responses in insular cortex (IC) were found over 3 months. 
Based on these findings we developed a working hypothesis on early and progressive emotion circuit 
changes that lead to PTSD development. To test this hypothesis, we propose to use a cohort of 
trauma survivors to identify early and progressive brain changes that contribute to, and that can 
be used to predict, chronic PTSD.
Trauma survivors recruited in Emergency Departments (EDs) will be longitudinally studied, starting 
within 2 weeks and out to 1 year after trauma. Functional MRI (fMRI) activation associated with 
processing, memory, and regulation of negative emotions will be studied in PTSD and non-PTSD trauma 
survivors using Shifted- attention Emotion Appraisal (SEAT) and Fear Conditioning (FCT) tasks. 
Structural MRI (sMRI) will examine structures in brain emotion circuits. Early brain functional and 
structural differences and symptoms in survivors who do versus do not develop PTSD at 1 year after 
trauma will be identified and analyzed using machine learning approaches to predict PTSD versus 
non-PTSD outcomes. Differences over time in brain function and structure in PTSD and non-PTSD 
survivors will be identified, and associations between these differences and progressions of 
symptoms will be examined. The proposed work fills an important gap in current understanding by 
identifying early and progressive brain changes that contribute to PTSD development. Our approach 
can serve to identify brain-based markers for PTSD development and to identify trauma survivors at 
high risk for chronic PTSD.

## Key facts

- **NIH application ID:** 10004715
- **Project number:** 5R01MH110483-05
- **Recipient organization:** UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
- **Principal Investigator:** Xin Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $658,730
- **Award type:** 5
- **Project period:** 2016-09-23 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004715

## Citation

> US National Institutes of Health, RePORTER application 10004715, Study of early brain alterations that predict development of chronic PTSD (5R01MH110483-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10004715. Licensed CC0.

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