Amygdala response to negative stimuli predicts PTSD symptom onset following a terrorist attack

Abstract

Objective: Individuals with posttraumatic stress disorder (PTSD) exhibit heightened amygdala reactivity and atypical activation patterns in the medial prefrontal cortex (mPFC) in response to negative emotional information. It is unknown whether these aspects of neural function are risk factors for PTSD or consequences of either trauma exposure or onset of the disorder. We had a unique opportunity to investigate this issue following the terrorist attacks at the 2013 Boston Marathon and the ensuing manhunt and shelter in place order. We examined associations of neural function measured prior to the attack with PTSD symptom onset related to these events.

Methods: A sample of 15 adolescents (mean age = 16.5 years) who previously participated in a neuroimaging study completed a survey assessing posttraumatic symptoms related to the terrorist attack. We examined blood oxygen level dependent (BOLD) response to viewing and actively down-regulating emotional responses to negative stimuli in regions previously associated with PTSD, including the amygdala, hippocampus, and mPFC, as prospective predictors of posttraumatic symptom onset.

Results: Increased BOLD signal to negative emotional stimuli in the left amygdala was strongly associated with posttraumatic symptoms following the attack. Reduced bilateral hippocampal activation during effortful attempts to down-regulate emotional responses to negative stimuli was also associated with greater posttraumatic symptoms. Associations of amygdala reactivity with posttraumatic symptoms were robust to controls for pre-existing depression, anxiety, and PTSD symptoms and prior exposure to violence.

Conclusions: Amygdala reactivity to negative emotional information might represent a neurobiological marker of vulnerability to traumatic stress and, potentially, a risk factor for PTSD.

Keywords: amygdala; hippocampus; posttraumatic stress disorder; stress; terrorism; trauma.

Figure 1

Structural regions of interest (ROIs) for cortical and subcortical regions. Three regions within medial prefrontal cortex (mPFC) were examined. These included dorsal anterior cingulate cortex (light purple; caudal_acc), rostral anterior cingulate cortex (dark purple; rostral_acc) and ventromedial prefrontal cortex (pink; medial orbitofrontal and frontal pole). All regions of interest are defined anatomically based on the individual’s own anatomy using FreeSurfer and shown on the expanded cortical surface for viewing purposes; cortical regions were defined using the 2005 segmentation atlas. Within the subcortex two regions were identified: the amygdala (blue) and hippocampus (yellow). All regions shown here are from individual representative subject’s aparc (cortex) and aseg (subcortex) segmentation. Activation during contrasts of interest was extracted from within the entire structure for each ROI.

Figure 2

Amygdala reactivity to negative vs. neutral images and PTSD symptoms related to the Boston Marathon terrorist attack. Left amygdala activation for the contrast of look negative > look neutral. Model controls for age, gender, time since scan, and symptoms of depression and anxiety prior to the attack; R² represents contribution of amygdala activity over and above these covariates.

Figure 3

Hippocampal activation during effortful emotion regulation vs. viewing negative images and PTSD symptoms related to the Boston Marathon terrorist attack. Left hippocampal activation for the contrast of decrease > look negative. Model controls for age, gender, time since scan, and symptoms of depression and anxiety prior to the attack; R² represents contribution of hippocampal activity over and above these covariates.