Abnormal gray matter volume and structural covariance network of basal ganglia-limbic system in patients with major...

Major Depressive Disorder (MDD) is a highly prevalent neurological disorder, characterized by multidimensional symptoms that are associated with structural abnormalities across multiple brain networks. There remains a lack of systematic research into the core regions and brain maturational disruption underlying the symptoms of MDD. In this study, we aimed to assess aberrant gray matter volume (GMV) and structural covariance network (SCN) in patients with MDD compared to healthy controls.

T1-weighted anatomical images of 159 patients with MDD and 121 matched healthy controls were acquired. 17-item Hamilton Depression Rating Scale (HAMD-17) was utilized to assess the clinical symptoms of MDD. Voxel-based morphometry was utilized to assess the core aberrancies of GMV in patients with MDD; a novel Gaussian kernel-based density estimation was employed to construct the individual-based SCN, network-based statistic was applied to investigate the interregional structural coordinated changes; Pearson's correlation was applied to assess the association between these abnormalities and clinical severity in MDD.

Patients with MDD showed increased GMV mainly in the basal ganglia (putamen), limbic system (parahippocampal gyrus, amygdala), inferior temporal gyrus and olfactory, while decreased GMV in the diencephalic nuclei (thalamus) and precentral gyrus. SCN analyses reveal an abnormal network centered on the pallidum and hippocampus as core nodes, which encompasses three functional subnetworks: the emotional regulation network, sensorimotor network, and cognitive control network. Moreover, the decreased GMV in the thalamus and increased structural coordination between the pallidum and the parahippocampal gyrus is significantly correlated with patients' HAMD-17 scores.

Our findings suggest the pathophysiology of MDD may primarily lie in the abnormal morphology and interregional coordinated development of the basal ganglia-limbic system. The current results provided novel supplementary evidence for the hypothesis of structural aberrations in MDD.