A prospective study of pre-trauma fear learning and extinction as risk factors for posttraumatic stress disorder.

Identifying risk for developing trauma-related disorders is a critical step in future prevention and intervention strategies. Impairments in inhibition of learned fear, such as safety signal learning and fear extinction, are suggested to be core mechanisms underlying symptom development and maintenance of posttraumatic stress disorder (PTSD). However, it is unclear if these impairments are pre-existing risk factors for PTSD, or if fear inhibition abnormalities arise only after trauma and symptom development. We utilized a prospective-longitudinal study in human, male service members at high risk for trauma exposure to test the hypothesis that learned fear impairments are pre-existing risk factors for PTSD. PTSD symptoms, fear learning, and fear extinction were assessed prior to a 7-month combat deployment to Afghanistan and 4-6 months after return (final N = 643). Fear learning and extinction were measured by fear-potentiated startle, self-reported anxiety, and threat expectancy ratings. Poor discrimination between threat and safety signals before trauma predicted higher likelihood for development of new onset PTSD after trauma, but not PTSD severity. This effect remained when controlling for trauma exposure. Lower fear extinction learning rate at the pre-trauma time-point predicted PTSD severity but not PTSD status. These findings support the hypothesis that both overgeneralization of fear and/or poor safety signal learning as well as slower fear extinction learning may predispose individuals for development of PTSD. These findings support further study of cue discrimination and slow fear extinction learning as "intermediate phenotypes" for intervention strategies and mechanistic studies targeting the neurobiology of risk and resilience to trauma-related disorders.