More Than Just Fear: A New Profile of Post-traumatic Stress Disorder

Trauma may be even more complex than previously thought. Post-traumatic stress disorder (PTSD) is often portrayed in popular media as subjects experiencing hypervigilance, flashbacks, and nightmares. While these fear-based symptoms do commonly occur, new research from Yale School of Medicine (YSM) shows another distinct side to PTSD.

“PTSD is highly heterogeneous, yet most diagnostic frameworks and treatment models have historically centered on fear-related processes,” says Ziv Ben-Zion, PhD, assistant professor adjunct at YSM and assistant professor at University of Haifa. “We hypothesized that fear captures only part of the clinical picture.”

For several years, Ilan Harpaz-Rotem, PhD, ABPP, Glenn H. Greenberg Professor of Psychiatry at YSM and professor of psychology in Yale’s Faculty of Arts and Sciences, has worked with his research team to understand the unique biology underlying this complex condition. Now, according to a study published recently in Biological Psychiatry, the team—which also includes Tobias Spiller, MD, and Or Duek, PhD, both assistant professors adjunct in psychiatry at YSM—found that PTSD involves both fear and emotional pain responses.

Untangling these two distinct symptom profiles could potentially inform future treatments of the condition.

“We identified two clinical profiles with distinct neural signatures, underscoring that PTSD is not reducible to fear alone,” says Ben-Zion, first author of the study. “Clinically, this suggests that assessment and treatment should be guided by the individual’s dominant emotional experience, whether fear-based or driven by emotional pain.”

The research drew from two different analyses. In the first, more than 800 trauma-exposed individuals completed a PTSD symptom checklist, and the researchers assessed the connections between different symptoms, which revealed the two distinct profiles. While the fear profile was associated with classic “threat-reactivity” symptoms—flashbacks, exaggerated startle response, nightmares, distressing memories, and avoiding external reminders—the emotional pain profile was associated more with internal distress, including loss of interest, negative beliefs, negative emotions, trouble sleeping, and emotional reactivity.

Interestingly, when participants were asked how their symptoms interfered with daily life, almost 70% rated emotional pain as more impairing than fear.

Given these findings, the researchers were interested in exploring the potential underlying neural correlates of the symptom profiles.

In the second analysis, conducted with the help of Dustin Scheinost, PhD, associate professor of radiology and biomedical imaging at YSM, and Alexander Simon, a PhD student in the Interdepartmental Neuroscience Program at YSM, the team used functional magnetic resonance imaging (fMRI) to assess whole-brain connectivity patterns in 162 recent trauma survivors. Based on these patterns, the researchers then attempted to predict the severity of fear-based or emotional pain-based symptoms 14 months later.

“We examined whole-brain connectivity patterns, focusing on large-scale networks and their dynamic interactions rather than isolated regions,” Ben-Zion says. “Using brain connectivity measured shortly after trauma, we then predicted symptom severity 14 months later.”

The connectivity patterns that the team identified were only predictive of fear-based symptoms, not emotional pain. But the finding is still exciting, the researchers say. Because the patterns were only predictive of fear symptoms, it suggests that there may be different neural mechanisms underlying the two profiles, thus validating the existence of this new model in the first place, a finding that transcended two different studies with two different cohorts across two different time periods and geographical locations.

“One of the central goals in PTSD research is to identify principles that generalize across populations,” Ben-Zion says. “Seeing the fear versus emotional pain distinction replicate across independent samples strengthened our confidence in the model.”

Understanding the difference between fear and emotional pain in PTSD could potentially inform new treatment approaches and may shift the way that providers and patients think about the condition.

“Our laboratory at Yale is really looking into precision psychiatry of post-traumatic stress disorder because a lot of medications fail,” says Harpaz-Rotem, senior investigator of the study. “When you are trying to develop a treatment, you want to think about the things that drive the psychopathology in that specific individual.”

It all starts with a simple question, according to Ben-Zion.

“In terms of changing the way people look at PTSD, all the models from 40 to 50 years ago focused on fear and most of the treatments, both medication and psychological, are based on trying to reduce fear levels. This is one piece of the puzzle, and for some people it works, but it doesn’t work for others,” he says. “A simple but powerful clinical question is whether fear or emotional pain is driving a patient’s distress. Centering treatment on that dominant emotional experience may lead to more precise and effective care.”