MRI signature of brain age underlying post-traumatic stress disorder in World Trade Center responders
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 (BAD<sub>no_PTSD</sub> = -0.43 y; BAD<sub>WTC_PTSD</sub> = 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.
Authors
- Francesco La Rosa (ORCID: https://orcid.org/0000-0002-9224-4664)
- Cheuk Y. Tang (ORCID: https://orcid.org/0000-0002-9828-0092)
- Evelyn J. Bromet (ORCID: https://orcid.org/0000-0002-2648-5793)
- Megan K. Horton (ORCID: https://orcid.org/0000-0002-8139-5918)
- Sean Clouston (ORCID: https://orcid.org/0000-0002-6124-0329)
- Stephanie Santiago‐Michels (ORCID: https://orcid.org/0000-0002-9041-771X)
- Alison C. Pellecchia (ORCID: https://orcid.org/0000-0003-0150-289X)
- R. Sean Morrison
- Elza Rechtman (ORCID: https://orcid.org/0000-0002-5034-6048)
- Roberto G. Lucchini (ORCID: https://orcid.org/0000-0002-9723-0237)
- Azzurra Invernizzi (ORCID: https://orcid.org/0000-0001-7411-8552)
- Benjamin J. Luft (ORCID: https://orcid.org/0000-0001-9008-7004)
- Ismail Nabeel (ORCID: https://orcid.org/0000-0002-6909-1970)
- Erin Beck (ORCID: https://orcid.org/0000-0001-7839-7958)
- Anna Sather
Institutions
- The Graduate Center, CUNY (US)
- City University of New York (US)
- Florida International University (US)
- Stony Brook School (US)
- Stony Brook University (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Translational Psychiatry
- Published
- 2025-11-28
- DOI
- https://doi.org/10.1038/s41398-025-03769-7
- Citations
- 1
- Primary Topic
- Posttraumatic Stress Disorder Research
- Type
- article
- Field-Weighted Citation Impact
- 2.31
Funders
- National Science Foundation
- U.S. Department of Defense
- Georgia Clinical and Translational Science Alliance
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institutes of Health
- Centers for Disease Control and Prevention
- National Institute on Aging
- National Institute of Neurological Disorders and Stroke
- National Institute for Occupational Safety and Health