Structural and functional deficits and couplings in the cortico-striato-thalamo-cerebellar circuitry in social anxiety disorder

Although functional and structural abnormalities in brain regions involved in the neurobiology of fear and anxiety have been observed in patients with social anxiety disorder (SAD), the findings have been heterogeneous due to small sample sizes, demographic confounders, and methodological differences. Besides, multimodal neuroimaging studies on structural-functional deficits and couplings are rather scarce. Herein, we aimed to explore functional network anomalies in brain regions with structural deficits and the effects of structure-function couplings on the SAD diagnosis. High-resolution structural magnetic resonance imaging (MRI) and resting-state functional MRI images were obtained from 49 non-comorbid patients with SAD and 53 demography-matched healthy controls. Whole-brain voxel-based morphometry analysis was conducted to investigate structural alterations, which were subsequently used as seeds for the resting-state functional connectivity analysis. In addition, correlation and mediation analyses were performed to probe the potential roles of structural-functional deficits in SAD diagnosis. SAD patients had significant gray matter volume reductions in the bilateral putamen, right thalamus, and left parahippocampus. Besides, patients with SAD demonstrated widespread resting-state dysconnectivity in cortico-striato-thalamo-cerebellar circuitry. Moreover, dysconnectivity of the putamen with the cerebellum and the right thalamus with the middle temporal gyrus/supplementary motor area partially mediated the effects of putamen/thalamus atrophy on the SAD diagnosis. Our findings provide preliminary evidence for the involvement of structural and functional deficits in cortico-striato-thalamo-cerebellar circuitry in SAD, and may contribute to clarifying the underlying mechanisms of structure-function couplings for SAD. Therefore, they could offer insights into the neurobiological substrates of SAD.