ObjectiveTo explore the interhemispheric information synergy ability of the brain in major depressive disorder (MDD) patients by applying the voxel-mirrored homotopic connectivity (VMHC) method and further explore the potential clinical diagnostic value of VMHC metric by a machine learning approach.Methods52 healthy controls and 48 first-episode MDD patients were recruited in the study. We performed neuropsychological tests and resting-state fMRI scanning on all subjects. The VMHC values of the symmetrical interhemispheric voxels in the whole brain were calculated. The VMHC alterations were compared between two groups, and the relationship between VMHC values and clinical variables was analyzed. Then, abnormal brain regions were selected as features to conduct the classification model by using the support vector machine (SVM) approach.ResultsCompared to the healthy controls, MDD patients exhibited decreased VMHC values in the bilateral middle frontal gyrus, fusiform gyrus, medial superior frontal gyrus and precentral gyrus. Furthermore, the VMHC value of the bilateral fusiform gyrus was positively correlated with the total Hamilton Depression Scale (HAMD). Moreover, SVM analysis displayed that a combination of all clusters demonstrated the highest area under the curve (AUC) of 0.87 with accuracy, sensitivity, and specificity values of 86.17%, 76.74%, and 94.12%, respectively.ConclusionMDD patients had reduced functional connectivity in the bilateral middle frontal gyrus, fusiform gyrus, medial superior frontal gyrus and precentral gyrus, which may be related to depressive symptoms. The abnormality in these brain regions could represent potential imaging markers to distinguish MDD patients from healthy controls.