Amygdala hyperactivity in PTSD: disentangling predisposing from consequential factors in a prospective longitudinal design.

Abstract

Background: Substantial inter-individual differences exist in the vulnerability to develop post-traumatic stress disorder (PTSD) symptoms following trauma exposure. Identification of neurocognitive risk markers for PTSD-symptoms could aid early assessment and identification of preventive intervention-targets for PTSD, particularly in high-risk professionals. Therefore, large prospective longitudinal studies with pre-trauma measurements are essential to disentangle whether previously observed neurobiological alterations in PTSD are a cause or consequence of trauma exposure or PTSD symptoms.

Methods: In police recruits (n=221) without current trauma symptoms but at high risk for trauma exposure, we employed functional magnetic resonance imaging (fMRI) to disentangle predictive and acquired neural markers of post-traumatic stress symptoms. Using an experimental paradigm, we investigated anticipatory threat responses and the switch into defensive action.

Results: Those recruits who showed relatively heightened dorsal amygdala responses and heightened amygdala-precuneus coupling during threat anticipation demonstrated relatively stronger increase in PTSD symptoms after trauma exposure. While the experience of traumatic events, independent of PTSD symptoms, was associated with increased lateral amygdala activation in response to the aversive stimulus (i.e. receiving an electrical shock).

Conclusions: This prospective longitudinal study shows a predictive role for dorsal amygdala responsivity during threat anticipation for the development of trauma symptoms, while lateral amygdala responding to aversive events after trauma may reflect a failure to regulate. Our findings not only inform neurobiological theories of PTSD risk and vulnerability but also provide a starting point for prediction and intervention studies.