Disrupted interhemispheric resting-state functional connectivity and structural connectivity in first-episode, treatment-naïve generalized anxiety disorder

Abstract Background Aberrant functional and structural connectivity are considered to be involved in the underlying neural mechanism of generalized anxiety disorder (GAD). However, alterations in functional and structural interactions between the bilateral hemispheres are rarely examined. The current study aimed to characterized interhemispheric resting-state functional connectivity and white matter microstructural integrity of the corpus callosum in patients with GAD. Methods Resting-state Blood oxygen level-dependent and diffusion tensor image were acquired for patients with GAD and healthy subjects. The two groups were matched in age, gender, education years. The voxel-mirrored homotopic connectivity (VMHC) of whole brain and white matter integrity of the corpus callosum (CC) were compared between the two groups. Their correlations with clinical measures were further performed. Results Compare to controls, decreased resting-state VMHC were found in the precentral gyrus, middle cingulate gyrus and insula/putamen in patients with GAD. No regions of increased VMHC were detected in GAD. Compared to controls, GAD patients showed decreased fractional anisotropy (FA) values in CC2. In GAD group, further Pearson's correlation analyses showed that VMHC of the midcingulate gyrus positively correlated with FA of CC2, FA of CC2 negatively correlated with anxiety severity. Further mediation analyses demonstrated that attenuated VMHC in bilateral midcingulate gyrus partly mediated the association between white matter integrity of CC2 sub-region and anxiety severity. Conclusion Our findings suggested impairment of interhemispheric coordination in GAD. Moreover, disrupted interhemispheric connectivity correlated with anxiety severity in GAD. Our findings provided a novel clue about the neural mechanism of GAD, and may contribute to further deep exploration and treatment of GAD. Limitations The study was lack of comparison with non-GAD anxiety disorders.