Aberrant Inter-hemispheric Connectivity in Patients With Recurrent Major Depressive Disorder: A Multimodal MRI Study

OBJECTIVE: Inter-hemispheric network dysconnectivity has been well-documented in patients with recurrent major depressive disorder (MDD). However, it has remained unclear how structural networks between bilateral hemispheres relate to inter-hemispheric functional dysconnectivity and depression severity in MDD. Our study attempted to investigate the alterations in corpus callosum macrostructural and microstructural as well as inter-hemispheric homotopic functional connectivity (FC) in patients with recurrent MDD and to determine how these alterations are related with depressive severity. MATERIALS AND METHODS: Resting-state functional MRI (fMRI), T1WI anatomical images and diffusion tensor MRI of the whole brain were performed in 140 MDD patients and 44 normal controls matched for age, sex, years of education. We analyzed the macrostructural and microstructural integrity as well as voxel-mirrored homotopic functional connectivity (VMHC) of corpus callosum (CC) and its five subregion. Two-sample t-test was used to investigate the differences between the two groups. Significant subregional metrics were correlated with depression severity by spearman's correlation analysis, respectively. RESULTS: Compared with control subjects, MDD patients had significantly attenuated inter-hemispheric homotopic FC in the bilateral medial prefrontal cortex, and impaired anterior CC microstructural integrity (each comparison had a corrected P < 0.05), whereas CC macrostructural measurements remained stable. In addition, disruption of anterior CC microstructural integrity correlated with a reduction in FC in the bilateral medial prefrontal cortex, which correlated with depression severity in MDD patients. Furthermore, disruption of anterior CC integrity exerted an indirect influence on depression severity in MDD patients through an impairment of inter-hemispheric homotopic FC. CONCLUSION: These findings may help to advance our understanding of the neurobiological basis of depression by identifying region-specific interhemispheric dysconnectivity.