Summary: New research reveals that witnessing trauma triggers unique brain changes, distinct from those caused by experiencing trauma firsthand. The study found that indirect trauma leads to different protein degradation patterns in key brain regions involved in fear memory.
Researchers also identified sex-specific differences, which may explain why women are twice as likely to develop PTSD. These findings suggest that bystander PTSD may require different treatment strategies, paving the way for more targeted therapies.
Key Facts:
- Distinct Brain Changes: Witnessing trauma alters brain protein degradation patterns differently than experiencing trauma firsthand.
- Sex-Specific Differences: Women’s brains process indirect fear memories differently, possibly explaining their higher PTSD risk.
- New Treatment Potential: Findings highlight the need for targeted PTSD therapies based on trauma type and biological factors.
Source: Virginia Tech
For years, post-traumatic stress disorder (PTSD) has been studied primarily in people who experience trauma firsthand.
But what about those who witness it — military veterans, first responders, health care workers, or bystanders to violence — who constitute 10 percent of all PTSD cases?
New research from Virginia Tech, published in PLOS ONE, reveals that witnessing trauma triggers unique brain changes, distinct from those caused by experiencing trauma firsthand.
The study is the first to shed light on the molecular differences between directly acquired PTSD and bystander PTSD and could pave the way for changes in how the disorders are treated.
“Currently, patients with directly acquired PTSD and bystander PTSD are treated the same way – with a combination of therapy and medication,” said Timothy Jarome, the project’s principal investigator and associate professor of neurobiology in the College of Agriculture and Life Sciences.
“Our research suggests that indirect trauma and direct trauma create different biological responses, which could mean they require different treatment strategies that target distinct brain pathways.”
Understanding how observation leads to PTSD
Jarome’s research focuses on understanding the neurobiological mechanisms behind memory-related disorders, including PTSD, dementia, and Alzheimer’s disease. His interest in bystander PTSD arose after learning about PTSD symptoms reported in people who witnessed the deadly 2021 collapse of a Miami condominium.
“People who saw it from across the street reported that they were suffering from nightmares, insomnia, and anxiety,” he said.
“They were showing symptoms of PTSD, but didn’t go through it or have any connection to the people in the building. We sought out to understand the brain mechanisms behind how that occurred.”
For the study, researchers focused on protein changes caused by a fear stimulus in three key brain regions involved in fear memory: the amygdala, the anterior cingulate cortex, and the retrosplenial cortex. They discovered that witnessing trauma triggered distinct protein degradation patterns in all three regions, compared to directly experiencing trauma.
Additionally, they uncovered sex-specific differences in how male and female brains process indirect fear memories.
These findings build on previous research from Jarome’s lab, which identified a specific protein, known as K-63 ubiquitin, linked to PTSD development in women.
“Our findings highlight significant biological differences in how male and female brains respond to witnessing trauma,” said the paper’s lead author, Shaghayegh Navabpour, a former Ph.D. student in translational biology, medicine, and health who is now a postdoctoral researcher at Stanford University.
“These differences may help explain why women are twice as likely as men to develop PTSD, leading to more targeted treatments that consider these sex-specific factors.”
In future research, Jarome hopes to explore how these how these molecular pathways could be leveraged to develop more precise PTSD therapies. He also hopes to examine the role of empathy, which originates in a different brain region called the anterior insular cortex, in bystander PTSD.
The vital role of student researchers
The research was funded by a $420,000 grant from the National Institute of Mental Health, which is part of the National Institutes of Health. In addition to supporting equipment and materials costs of the research, the grant helped pay the stipends of graduate and undergraduate research assistants on the project.
“At academic institutions, students — undergraduate, graduate, and postdocs — are the driving force for research,” Jarome said.
“While faculty members might secure the funding to do the projects, the reality is that the work is done by these students as they’re going through their training. Without graduate students, especially, but also undergraduates and postdocs, science doesn’t advance.”
Navabpour, who earned her Ph.D. from Virginia Tech in 2023, is now working at Stanford to develop a drug to help treat Alzheimer’s disease.
“My time in Dr. Jarome’s lab was hugely valuable in shaping my career and preparing me for my current role as a postdoc and my goal of becoming a faculty member,” she said.
“I learned how to think scientifically — how to ask the right questions and approach problems critically — and gained hands-on experience with key methods and techniques that continue to inform my research.”
About this neuroscience and PTSD research news
Author: Margaret Ashburn
Source: Virginia Tech
Contact: Margaret Ashburn – Virginia Tech
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Indirectly acquired fear memories have distinct, sex-specific molecular signatures from directly acquired fear memories” by Timothy Jarome et al. PLOS One
Abstract
Indirectly acquired fear memories have distinct, sex-specific molecular signatures from directly acquired fear memories
Post-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects women more than men. About 30% of patients suffering from PTSD develop the disorder by witnessing a traumatic event happen to someone else.
However, as the focus has remained on those directly experiencing the traumatic event, whether indirectly acquired fear memories that underlie PTSD have the same molecular signature as those that are directly acquired remains unknown.
Here, using a rodent indirect fear learning paradigm where one rat (observer) watches another rat (demonstrator) associate an auditory cue with foot shock, we found that fear can be indirectly acquired by both males and females regardless of the sex or novelty (familiarity) of the demonstrator animal.
However, behaviorally, indirectly acquired fear responses resemble those of pseudoconditioning, a behavioral response that is thought to not represent learning.
Despite this, using unbiased proteomics, we found that indirectly acquired fear memories have distinct protein degradation profiles in the amygdala and anterior cingulate cortex (ACC) relative to directly acquired fear memories and pseudoconditioning, which further differed significantly by sex.
Additionally, Egr2 and c-fos expression in the retrosplenial cortex of observer animals resembled that of demonstrator rats but was significantly different than that of pseudoconditioned rats.
Together, these findings reveal that indirectly acquired fear memories have sex-specific molecular signatures that differ from those of directly acquired fear memories or pseudoconditioning.
These data have important implications for understanding the neurobiology of indirectly acquired fear memories that may underlie bystander PTSD.
