Anxiety disorders are common, debilitating, and challenging to treat, highlighting the importance of understanding the mechanisms underlying them. Like other neuropsychiatric disorders, anxiety is widely thought to emerge from aberrant communication in brain networks. Evidence gleaned from human imaging studies and nonhuman animal models highlights the importance of the amygdala, yet little is known about the architecture of the large-scale circuitry that regulates amygdala function and, ultimately, expression of the anxious phenotype. This intermediate level symposium brings together compelling new evidence from monkeys, children, and adults, including patients and at-risk populations, highlighting the role of alterations in intrinsic functional connectivity between the amygdala and prefrontal cortex (PFC). First, we will present work conducted with large samples of healthy children that suggests a typical developmental trajectory of amygdala- medial PFC functional connectivity. This provides an essential foundation for understanding how alterations in these circuits may underlie the onset of anxiety early in development. Second, we will demonstrate how early temperamental risk for anxiety, in both primates and humans, is associated with disruption of these circuits. Such findings are found even in adults who exhibited temperamental risk as children but never developed clinical anxiety, suggesting lingering biomarkers of risk. Finally, we will present findings of anxiety-related alterations in amygdala- PFC functional connectivity from studies of pediatric and adult samples. These convergent lines of evidence provide a novel neurobiological model for understanding the mechanisms that contribute to the development and maintenance of anxiety and set the stage for developing improved intervention strategies.
