A causal model of post-traumatic stress disorder: disentangling predisposed from acquired neural abnormalities

• PTSD is triggered by well-delineated stressors, facilitating causal brain models.
• Amygdala and dACC abnormalities confer vulnerability for increased fear upon stress.
• Reduced hippocampus–vmPFC connectivity following stress may impair fear inhibition.
• The functions of these brain circuits imply a temporal trajectory of PTSD symptoms.

Discriminating neural abnormalities into the causes versus consequences of psychopathology would enhance the translation of neuroimaging findings into clinical practice. By regarding the traumatic encounter as a reference point for disease onset, neuroimaging studies of post-traumatic stress disorder (PTSD) can potentially allocate PTSD neural abnormalities to either predisposing (pre-exposure) or acquired (post-exposure) factors. Based on novel research strategies in PTSD neuroimaging, including genetic, environmental, twin, and prospective studies, we provide a causal model that accounts for neural abnormalities in PTSD, and outline its clinical implications. Current data suggest that abnormalities within the amygdala and dorsal anterior cingulate cortex represent predisposing risk factors for developing PTSD, whereas dysfunctional hippocampal–ventromedial prefrontal cortex (vmPFC) interactions may become evident only after having developed the disorder.