Enhanced Prefrontal-Amygdala Connectivity Following Childhood Adversity as a Protective Mechanism Against Internalizing in Adolescence

Abstract Background Much research has focused on the deleterious neurobiological effects of childhood adversity that may underlie internalizing disorders. Although most youth show emotional adaptation following adversity, the corresponding neural mechanisms remain poorly understood. Methods In this longitudinal community study, we examined the associations among childhood family adversity, adolescent internalizing symptoms, and their interaction on regional brain activation and amygdala/hippocampus functional connectivity during emotion processing in 132 adolescents. Results Consistent with prior work, childhood adversity predicted heightened amygdala reactivity to negative, but not positive, images in adolescence. However, amygdala reactivity was not related to internalizing symptoms. Furthermore, childhood adversity predicted increased prefrontal-amygdala connectivity to negative, but not positive, images, yet only in lower internalizing adolescents. Childhood adversity also predicted increased prefrontal-hippocampus connectivity to negative images but was not moderated by internalizing. These findings were unrelated to adolescent adversity or externalizing symptoms, suggesting specificity to childhood adversity and adolescent internalizing. Conclusions Together, these findings suggest that adaptation to childhood adversity is associated with augmentation of prefrontal-subcortical circuits specifically for negative emotional stimuli. Conversely, insufficient enhancement of prefrontal-amygdala connectivity, with increasing amygdala reactivity, may represent a neural signature of vulnerability for internalizing by late adolescence. These findings implicate early childhood as a critical period in determining the brain's adaptation to adversity and suggest that even normative adverse experiences can have a significant impact on neurodevelopment and functioning. These results offer potential neural mechanisms of adaptation and vulnerability that could be used in the prediction of risk for psychopathology following childhood adversity.