Accessible neurobehavioral anger-related markers for vulnerability to post-traumatic stress symptoms in a population of male soldiers

Identifying vulnerable individuals prone to develop post-traumatic stress symptoms (PTSS) is of paramount importance, especially in populations at high risk for stress exposure such as combat soldiers. While several neural and psychological risk factors are known, no post-traumatic stress disorder (PTSD) biomarker has yet progressed to clinical use. Here we present novel and clinically applicable angerrelated neurobehavioral risk markers for military-related PTSS in a large cohort of Israeli soldiers. The psychological, electrophysiological and neural (Simultaneous recording of scalp electroencephalography [EEG] and functional magnetic resonance imaging [fMRI]) reaction to an anger-inducing film were measured prior to advanced military training and PTSS were recorded at 1-year follow-up. Limbic modulation was measured using a novel approach that monitors amygdala modulation using fMRI-inspired EEG, hereafter termed amygdala electrical fingerprint (amyg-EFP). Inter-subject correlation (ISC) analysis on fMRI data indicated that during movie viewing participants’ brain activity was synchronized in limbic regions including the amygdala. Self-reported state-anger and amyg-EFP modulation successfully predicted PTSS levels. Stateanger significantly accounted for 20% of the variance in PTSS, and amyg-EFP signal modulation significantly accounted for additional 15% of the variance. Our study was limited by the moderate PTSS levels and lack of systematic baseline symptoms assessment. These results suggest that pre-stress neurobehavioral measures of anger may predict risk for later PTSS, pointing to anger-related vulnerability factors that can be measured efficiently and at a low cost before stress exposure. Possible mechanisms underlying the association between the anger response and risk for PTSS are discussed.