Magnetic resonance imaging (MRI) studies have indicated that the structure deficits and resting-state functional connectivity (FC) imbalances in cortico-limbic circuitry might underline the pathophysiology of MDD. Using structure and functional MRI, our aim is to investigate gray matter abnormalities in patients with treatment-resistant depression (TRD) and treatment-responsive depression (TSD), and test whether the altered gray matter is associated with altered FC. Voxel-based morphometry was used to investigate the regions with gray matter abnormality and FC analysis was further conducted between each gray matter abnormal region and the remaining voxels in the brain. Using one-way analysis of variance, we found significant gray matter abnormalities in the right middle temporal cortex (MTG) and bilateral caudate among the TRD, TSD and healthy controls. For the FC of the right MTG, we found that both the patients with TRD and TSD showed altered connectivity mainly in the default-mode network (DMN). For the FC of the right caudate, both patient groups showed altered connectivity in the frontal regions. Our results revealed the gray matter reduction of right MTG and bilateral caudate, and disrupted functional connection to widely distributed circuitry in DMN and frontal regions, respectively. These results suggest that the abnormal DMN and reward circuit activity might be biomarkers of depression trait.
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