Amygdala-Based Structural Covariance and Functional Connectivity Alterations in Patients with Generalized Anxiety Disorder

Abstract The available literature has shown widespread brain structural and functional changes in patients with generalized anxiety disorder (GAD), of which the deficits in the amygdala-based circuits were the most consistent findings and played key role in underpinning the neural mechanisms of GAD. However, ample studies were primarily focused on the amygdala-related structural or functional alterations, considerably less is known about their covariations. To address this issue, we separately calculated the amygdala-based structural covariance (SC) and functional connectivity (FC) in GAD, and then explored their common changes using conjunction analyses. We further tested the influences of the clinical characteristics of patients on the relationship between their amygdala-related structural and functional organization changes using moderation analyses. GAD patients exhibited reduced SC of the bilateral amygdala with regions involved in high order prefrontal, cingulate, and insula cortices, and showed decreased FC of the right amygdala with the bilateral anterior cingulate cortex (ACC) and right temporal pole. SC and FC covariations were observed in the right amygdala-bilateral ACC connectivity and such connectivity was modulated by illness duration of GAD. The amygdala-ACC structural and functional covariations and their interactions with the illness duration of GAD may extend our knowledge of pathological mechanisms of such disease.