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

November 28, 2025pubmed logopapers

Authors

Invernizzi A,La Rosa F,Sather A,Rechtman E,Nabeel I,Morrison RS,Pellecchia AC,Santiago-Michels S,Bromet EJ,Lucchini RG,Luft BJ,Clouston SA,Beck ES,Tang CY,Horton MK

Affiliations (12)

  • Department of Environmental Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected].
  • Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Windreich Department of Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Department of Environmental Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
  • World Trade Center Health and Wellness Program, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA.
  • Department of Psychology, The Graduate Center, City University of New York, New York, NY, USA.
  • Department of Psychiatry, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA.
  • Department of Environmental Health Sciences, Robert Stempel School of Public Health, Florida International University, Miami, FL, USA.
  • Department of Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA.
  • Program in Public Health and Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA.
  • Department of Radiology and Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

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 (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.

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