Differential Effects of Early Adversity and Posttraumatic Stress Disorder on Amygdala Reactivity: The Role of Developmental Timing

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with altered processing of threat-related stimuli. Neurobiological models implicate right amygdala hyperreactivity in these alterations, but this potential biomarker also has been observed in individuals exposed to adverse childhood experiences (ACEs) (i.e., abuse and neglect) without psychopathology. Separation of the differential contributions of PTSD and ACEs to amygdala reactivity might benefit from incorporating the developmental timing of the events. METHODS: We conducted comprehensive retrospective interviews assessing ACEs for each life year between the ages of 1 and 17 years in a sample of 60 women exposed to trauma (including 34 participants with PTSD and 26 healthy participants). Functional magnetic resonance imaging was used to extract amygdala reactivity to threatening versus neutral scenes. Amygdala reactivity was predicted from PTSD diagnosis, total ACE severity, and ACE severity by life year using random forest regression. RESULTS: PTSD and ACEs significantly predicted reactivity in the right amygdala (R-2 = 7%) but did not explain variance in the left amygdala. ACEs during both a prepubertal (ages 3 and 4) and a postpubertal (ages 16 and 17) period emerged as particularly predictive, while total ACE severity did not contribute to prediction. Follow-up analyses revealed a positive relationship between amygdala activity and PTSD and a negative relationship between amygdala activity and ACEs during predictive life years. CONCLUSIONS: The opposing effects of PTSD and ACEs caution against simplistic etiological and diagnostic interpretations of amygdala function. The identification of potentially sensitive periods for the effects of ACEs on amygdala reactivity to threat may help to uncover interactions between traumatization and development. of PTSD.