TY - JOUR
T1 - MRI signature of brain age underlying post-traumatic stress disorder in World Trade Center responders
AU - Invernizzi, Azzurra
AU - La Rosa, Francesco
AU - Sather, Anna
AU - Rechtman, Elza
AU - Nabeel, Ismail
AU - Morrison, R. Sean
AU - Pellecchia, Alison C.
AU - Santiago-Michels, Stephanie
AU - Bromet, Evelyn J.
AU - Lucchini, Roberto G.
AU - Luft, Benjamin J.
AU - Clouston, Sean A.
AU - Beck, Erin S.
AU - Tang, Cheuk Y.
AU - Horton, Megan K.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2026/12
Y1 - 2026/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105027589824
U2 - 10.1038/s41398-025-03769-7
DO - 10.1038/s41398-025-03769-7
M3 - Article
C2 - 41315231
AN - SCOPUS:105027589824
SN - 2158-3188
VL - 16
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 23
ER -