PTSD Is Linked To Accelerated Brain Aging In World Trade Center First Responders

Post-traumatic stress disorder (PTSD) is traditionally recognized as a psychological condition associated with exposure to extreme events, such as violence, natural disasters, or terrorist attacks. However, growing evidence indicates that PTSD may affect not only mental health but also brain biology over time.

A new study conducted by researchers at the Icahn School of Medicine at Mount Sinai investigated this possibility in a particularly vulnerable group: first responders who participated in rescue and recovery operations following the September 11, 2001 attacks on the World Trade Center (WTC).

This study shows that World Trade Center first responders with PTSD exhibit accelerated brain aging, measured by artificial intelligence, suggesting that psychological trauma may have lasting biological effects on brain structure.

Post-traumatic stress disorder (PTSD) is traditionally recognized as a psychological condition associated with exposure to extreme events, such as violence, natural disasters, or terrorist attacks. However, growing evidence indicates that PTSD may affect not only mental health but also brain biology over time.

A new study conducted by researchers at the Icahn School of Medicine at Mount Sinai investigated this possibility in a particularly vulnerable group: first responders who worked in rescue and recovery operations after the September 11, 2001 attacks on the World Trade Center (WTC). About a quarter of the men and women who worked at the WTC site developed persistent and clinically significant PTSD.

Previous neuroimaging studies had already shown structural and functional differences in the brains of these first responders when compared to those who did not develop the disorder. However, it was still unclear whether these changes could be interpreted as a process of accelerated brain aging.

To answer this question, the researchers used a new biomarker called brain age. Brain age is an estimate of how “old” the brain appears to be based on its structural characteristics, regardless of the person's actual chronological age. When brain age is greater than actual age, it suggests accelerated brain aging.

The study was the first to apply this type of deep learning-based model to the WTC first responder population. The team used BrainAgeNeXt, an advanced artificial intelligence model trained with over 11,000 structural MRI scans.

Unlike traditional methods, this model directly analyzes complete brain images without the need to segment the brain into specific regions, which increases its robustness and sensitivity to detect subtle structural changes.

Researchers analyzed MRI scans of two groups of first responders: one group diagnosed with WTC-related PTSD and a control group, matched for age and sex, without PTSD. For each participant, the model predicted brain age, which was then compared to actual chronological age. The difference between these two measures, called the Brain Age Difference, indicates whether the brain appears younger or older than expected.

The results showed a clear difference between the groups. First responders without PTSD had brain ages close to or even slightly lower than their chronological age. In contrast, first responders with PTSD had brains that appeared, on average, about three years older than expected for their actual age. This difference was statistically robust and clinically relevant.

Furthermore, the researchers observed that the length of exposure to the WTC environment played an important role. The longer the period of work at Ground Zero, the greater the effect of PTSD on brain aging. This suggests that the combination of psychological trauma and prolonged exposure to an extreme environment can intensify structural changes in the brain over time.

These findings reinforce the idea that PTSD should not be understood solely as a psychological disorder, but also as a condition with measurable neurobiological consequences.

The accelerated brain aging observed in first responders with PTSD may help explain why individuals exposed to severe trauma have a higher risk of developing age-related neurological diseases later in life, such as cognitive deficits and neurodegenerative diseases.

From a clinical perspective, the study introduces brain age as a promising biomarker for monitoring the neurological health of trauma-exposed populations. This type of measurement may, in the future, assist in the early identification of individuals at higher risk, allowing for preventive interventions aimed at protecting brain health.

Taken together, the results indicate that the impact of psychological trauma can extend for decades, leaving detectable structural marks on the brain. Recognizing these changes is an important step toward fully understanding the consequences of PTSD and developing care strategies that consider both the mental and neurological health of people exposed to extreme traumatic events.

READ MORE:

MRI signature of brain age underlying post-traumatic stress disorder in World Trade Center responders

Azzurra Invernizzi, Francesco La Rosa, Anna Sather, Elza Rechtman, Ismail Nabeel, R. Sean Morrison, Alison C. Pellecchia, Stephanie Santiago-Michels, Evelyn J. Bromet, Roberto G. Lucchini, Benjamin J. Luft, Sean A. Clouston, Erin S. Beck, Cheuk Y. Tang, and Megan K. Horton 

Translational Psychiatry, 28 November 2025.

https://doi.org/10.1038/s41398-025-03769-7

Abstract:

Approximately 23% of the men and women who participated in rescue and recovery efforts at the 9/11 World Trade Center (WTC) site experience persistent, clinically significant post-traumatic stress disorder (PTSD). Recent structural and functional magnetic resonance imaging (MRI) studies demonstrate significant neural differences between WTC responders with and without PTSD. Here, we used brain age, a novel MRI-based data-driven biomarker optimized to detect accelerated structural aging and examined the impact of PTSD on this process. Using BrainAgeNeX, a novel convolutional neural network that bypasses brain parcellation and has been trained and validated on over 11,000 T1-weighted MRI scans, we predicted brain age in WTC responders with PTSD (WTC-PTSD, n = 47) and age/sex matched responders without PTSD (non-PTSD, n = 52). Brain Age Difference (BAD) was then calculated for each WTC responder by subtracting chronological age from brain age. We found that BAD was significantly older in WTC-PTSD compared to non-PTSD responders (BADno_PTSD = −0.43 y; BADWTC_PTSD = 3.07 y; p < 0.001). Further, we found that WTC exposure duration (months working on site) moderates the association between PTSD and BAD (p = 0.005). Our results suggest that brain age is a relevant marker of structural damage in WTC responders with and without PTSD. PTSD may be a risk factor for accelerated aging in trauma-exposed populations.