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

The men and women involved in rescue and recovery operations at the 9/11 World Trade Center (WTC) site have a greater prevalence (23%) of 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 BrainAgeNeXt, a novel convolutional neural network trained and validated on 11,574 magnetic resonance imaging (MRI) T1- weighted 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). Predicted Age Difference (PAD) was then calculated for each WTC responder by subtracting chronological age from brain age. A positive PAD indicates that the responders brain is aging faster than expected for their chronological age. We found that PAD is significantly greater with WTC-PTSD compared to non-PTSD responders (p < 0.001). Further, we found that WTC exposure duration (months working on site) moderates the association between PTSD and PAD (p=0.0050). Our results suggested that brain age is a valid biomarker to compare aging trajectories in responders with and without PTSD. In particular, PTSD may be a substantial risk factor for accelerated neurodegeneration in this vulnerable and aging population.