Differential effects of early adversity and PTSD on amygdala reactivity: The role of developmental timing

Abstract 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 has also been observed in individuals exposed to adverse childhood experiences (ACE; i.e. abuse and neglect) without psychopathology. Separating the differential contributions of PTSD and ACE to amygdala reactivity might benefit from incorporating the developmental timing of events. Methods We conducted comprehensive retrospective interviews assessing ACE for each life year between ages 1 and 17 in a sample of 60 trauma-exposed women (34 with PTSD, 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 ACE significantly predicted reactivity in the right amygdala (R2 = 7%) but explained no variance in the left amygdala. ACE during both a prepubertal (ages 3 & 4) and a postpubertal (ages 16 & 17) period emerged as particularly predictive, while total ACE severity did not contribute to prediction. Follow-up analyses revealed a positive relationship of amygdala activity with PTSD and a negative relationship with ACE during predictive life years. Conclusions The opposing effects of PTSD and ACE caution against simplistic etiological and diagnostic interpretations of amygdala function. The identification of potentially sensitive periods for ACE effects on amygdala reactivity to threat may help to uncover interactions between traumatization and development of PTSD.