Resting-State Cortical Network and Subcortical Hyperconnectivity in Youth With Generalized Anxiety Disorder in the...

Generalized anxiety disorder (GAD) frequently emerges during childhood or adolescence, yet few studies have examined functional connectivity differences in youth with GAD. Functional magnetic resonance imaging (fMRI) studies of adults with GAD have implicated multiple brain regions; however, frequent examination of individual brain seed regions and/or networks has limited a holistic view of GAD-associated differences. The current study therefore used resting-state fMRI data from the Adolescent Brain Cognitive Development (ABCD) Study to investigate connectivity in youths with GAD across multiple cortical networks and subcortical regions implicated in adult GAD, considering diagnosis changes across 2 assessment periods.

In 164 youths with GAD and 3158 healthy control participants, within- and between-network connectivity for 6 cortical networks and 6 subcortical regions was assessed using linear mixed-effect models. Changes in GAD-associated connectivity between baseline and 2-year follow-up were then compared for participants with continuous GAD, GAD at baseline and not follow-up (GAD remitters), and GAD at follow-up and not baseline (GAD converters) versus control participants.

Youths with GAD showed greater within-ventral attention network (VAN) connectivity and hyperconnectivity between the amygdala and cingulo-opercular network and between striatal regions and the cingulo-opercular, default mode, and salience networks (false discovery rate p < .05). Within-VAN connectivity decreased for GAD remitters between baseline and follow-up. Sensitivity analyses revealed that these hyperconnectivity patterns were not observed in youths with major depressive disorder (n = 19), separation anxiety (n = 33), or social anxiety disorder (n = 111) who did not have GAD.

Results indicate that GAD in childhood and adolescence is associated with altered subcortical to cortical network connectivity and that within-VAN hyperconnectivity, in particular, is associated with clinically significant GAD-specific symptoms.