Disrupted interhemispheric functional and structural connectivity in patients with major depressive disorder

Background: Major depressive disorder (MDD) is associated with disrupted interhemispheric cooperation. However, the relationship between structural and functional alterations in interhemispheric cooperation in patients with MDD remains unclear. We investigated the associations between voxel-mirrored homotopic connectivity (VMHC) and radial diffusivity (RD) within the corpus callosum (CC) and their links to depressive symptoms in patients with MDD. Methods: Sixty patients with MDD and 38 healthy controls (HCs) were assessed using resting-state functional MRI (rs-fMRI) and diffusion MRI (dMRI) to evaluate interhemispheric functional connectivity (VMHC) and structural integrity (RD) in the CC subregions. Group comparisons, correlation analyses, and mediation analyses were conducted to identify the significant differences, relationships, and indirect effects. Results: Patients with MDD showed significantly reduced VMHC in the bilateral postcentral gyrus and lingual gyrus and increased RD in the CC subregions CC3, CC4, and CC5, indicating impaired functional and structural connectivity. Lower VMHC in the lingual gyrus was negatively correlated with depressive severity, whereas increased RD in the CC4 and CC5 was positively correlated with depressive symptoms. Mediation analysis revealed that the VMHC in the lingual gyrus fully mediated the relationship between RD in CC5 and depressive symptoms, suggesting a pathway through which structural impairments may affect mood through abnormal functional connectivity. Limitations: The cross-sectional design limits the assessment of changes over time, and focusing solely on interhemispheric connectivity may overlook other networks involved in MDD. Conclusion: These findings provide preliminary evidence for disrupted interhemispheric coordination in MDD, with both functional and structural connectivity impairments linked to depressive symptoms. The mediating effect of the VMHC in the lingual gyrus highlights the potential role of interhemispheric connectivity in the pathophysiology of MDD. Our results provide an integrative perspective on the functional and microstructural organization of the brain in patients with MDD.