Dissociable salience and default mode network modulation in generalized anxiety disorder: a connectome-wide association study

Abstract Generalized anxiety disorder (GAD) is a common anxiety disorder experiencing psychological and somatic symptoms. Here, we explored the link between the individual variation in functional connectome and anxiety symptoms, especially psychological and somatic dimensions, which remains unknown. In a sample of 118 GAD patients and matched 85 healthy controls (HCs), we used multivariate distance-based matrix regression to examine the relationship between resting-state functional connectivity (FC) and the severity of anxiety. We identified multiple hub regions belonging to salience network (SN) and default mode network (DMN) where dysconnectivity associated with anxiety symptoms (P < 0.05, false discovery rate [FDR]-corrected). Follow-up analyses revealed that patient’s psychological anxiety was dominated by the hyper-connectivity within DMN, whereas the somatic anxiety could be modulated by hyper-connectivity within SN and DMN. Moreover, hypo-connectivity between SN and DMN were related to both anxiety dimensions. Furthermore, GAD patients showed significant network-level FC changes compared with HCs (P < 0.01, FDR-corrected). Finally, we found the connectivity of DMN could predict the individual psychological symptom in an independent GAD sample. Together, our work emphasizes the potential dissociable roles of SN and DMN in the pathophysiology of GAD’s anxiety symptoms, which may be crucial in providing a promising neuroimaging biomarker for novel personalized treatment strategies.