Altered Development of Amygdala-Anterior Cingulate Cortex Connectivity in Anxious Youth and Young Adults

Development of corticoamygdala circuitry underlies the maturation of emotion processing and regulation, and age-related changes in amygdala connectivity with anterior cingulate cortex (ACC) have been shown to mediate normative developmental decreases in anxiety. It remains unclear whether developmental changes in this circuitry relate to pathological anxiety in youth. The current functional magnetic resonance imaging study addresses this question by examining amygdala functional connectivity in anxious and healthy individuals spanning the developmental period from childhood through adulthood. Youth and young adults (ages 7-25) with current anxiety disorders (n = 57) and healthy comparison subjects (n = 61) completed a functional magnetic resonance imaging emotional face processing task known to elicit amygdala activation in youth and adults. We examined interaction effects of anxiety group and age on amygdala connectivity with frontolimbic regions during processing of happy, angry, and fearful faces. Anxiety interacted with age to predict amygdala-ACC connectivity across emotional faces. Among healthy youth and young adults, age was negatively related to connectivity. In contrast, age was positively associated with amygdala-ACC connectivity in the anxious group. Group effects were also observed on amygdala connectivity with midcingulate and middle frontal gyri. Effects of anxiety and age on amygdala activation were not significant. Results indicate that anxiety is characterized by altered patterns of age-related changes in amygdala connectivity during emotional face processing. Positive associations between age and amygdala-ACC connectivity among anxious youth and young adults may indicate failure to establish early bottom-up connections in childhood and/or less top-down regulation of the amygdala into adulthood. “