Influence of depression severity on interhemispheric functional integration: an analysis from the REST-meta-MDD database.

Major depressive disorder (MDD) is a pervasive mental disorder that significantly impairs functional capabilities, underscoring the necessity for precise stratification of its severity to facilitate tailored treatment. This study investigated the utility of voxel-mirrored homotopic connectivity (VMHC) derived from resting-state functional magnetic resonance imaging (fMRI) data as a neuroimaging biomarker to differentiate varying severities of MDD in a sample drawn from the REST-meta-MDD project, which included 392 first-episode MDD patients and 440 healthy controls (HC) from 9 sites. Patients were classified into mild to moderate and severe depression groups according to the 17-item Hamilton Depression Scale (HAMD) scores. VMHC differences between these subgroups and their associations with HAMD scores were further examined. The results revealed significant reductions in VMHC within the fusiform gyrus for patients with mild to moderate depression compared to HCs, alongside more extensive reductions across the insula, postcentral gyrus, and angular gyrus in severe depression. Notably, increased VMHC in the middle cingulate cortex was identified in severe MDD patients relative to those with mild to moderate depression, with this increase showed a significant positive correlation with the HAMD scores. Additionally, receiver operating characteristic (ROC) curve analysis demonstrated that VMHC values in these regions effectively differentiate patients from HCs and across varying severities of MDD. These findings suggest that VMHC could serve as a valuable metric for clinical diagnosis and the stratification of depression severity, providing insights into the underlying neurobiological mechanisms associated with the disorder.