Comparison of Resting-State Functional Connectivity Between Generalized Anxiety Disorder and Social Anxiety Disorder: Differences in the Nucleus Accumbens and Thalamus Network

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Background: Generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are distinguished by whether anxiety is limited to social situations. However, reports on the differences in brain functional networks between GAD and SAD are few. Our objective is to understand the pathogenesis of GAD and SAD by examining the differences in resting brain function between patients with GAD and SAD and healthy controls (HCs). Methods: This study included 21 patients with SAD, 17 patients with GAD, and 30 HCs. Participants underwent psychological assessments and resting-state functional magnetic resonance imaging. Whole-brain analyses were performed to compare resting-state functional connectivity (rsFC) among the groups. In addition, logistic regression analysis was conducted on the rsFC to identify significant differences between GAD and SAD. Results: Patients with SAD and GAD had significantly higher rsFC between the bilateral postcentral gyri and bilateral amygdalae/thalami than HCs. Compared with patients with SAD, those with GAD had significantly higher rsFC between the right nucleus accumbens and bilateral thalami and between the left nucleus accumbens and right thalamus. rsFC between the left nucleus accumbens and right thalamus positively correlated with state anxiety in patients with SAD and GAD, respectively. In addition, logistic regression analysis revealed that the right nucleus accumbens and the right thalamus connectivity could distinguish SAD from GAD. Conclusions: GAD and SAD were distinguished by the right nucleus accumbens and the right thalamus connectivity. Our findings offer insights into the disease-specific neural basis of SAD and GAD. Clinical Trial Registration Number: UMIN000024087. Impact Statement This study is the first to identify a resting state functional connectivity that distinguishes social anxiety disorder (SAD) from generalized anxiety disorder (GAD) and to clarify a common connectivity in both disorders. We found that the connectivity between the right nucleus accumbens and the right thalamus differentiated SAD from GAD. Furthermore, these rsFC differences suggest an underlying basis for fear overgeneralization. Our findings shed light on the pathophysiology of these conditions and could be used as a basis for further studies to improve outcomes for such patients.

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