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 per cent 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 by 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 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 PhD 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 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

"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."