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_{no_PTSD} = -0.43 y; BAD_{WTC_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.