Macroscopic structural abnormalities in the thalamus and thalamic circuits have been shown to contribute to the neuropathology of major depressive disorder (MDD). However, cytoarchitectonic properties underlying these macroscopic abnormalities remain unknown. The purpose of this study was to identify systematic deficits of brain architecture in depression, from structural brain network organization to microstructural properties. A multi-modal neuroimaging approach including diffusion, anatomical and quantitative magnetic resonance imaging (MRI) was used to examine structural-related alternations in 56 MDD patients compared with 35 age- and sex-matched controls. Structural networks were constructed and analyzed using seed-based probabilistic tractography. Morphometric measurements, including cortical thickness and voxel-based morphometry (VBM), were evaluated across the whole brain. A conjunction analysis was then conducted to identify key regions showing common structural alternations across modalities. The microstructural properties, macromolecular tissue volume (MTV) and T1 relaxation times of identified key regions were then calculated. Results showed multiple alterations of structural connectivity within a set of subcortical areas and their connections to cortical regions in MDD patients. These subcortical regions included the putamen, thalamus and caudate, which are predominately involved in the limbic-cortical-striatal-pallidal-thalamic network (LCSPT). Structural connectivity was disrupted within and between large-scale networks, mainly including subcortical networks, default mode networks and salience/ventral attention networks. Consistently, these regions also exhibited widespread volume reductions in MDD patients, specifically the bilateral thalamus, left putamen and right caudate. Importantly, the microstructural properties, T1 relaxation time of left thalamus were increased and negatively correlated with its gray matter volume in MDD patients. The present work to date sheds light on the neuropathological disruptions of LCSPT circuit in MDD, providing the first multi-modal neuroimaging evidence for the macro-micro structural abnormalities of the thalamus in patients with MDD. These findings have implications in understanding the abnormal changes of brain structures across development of MDD.
Microstructural deficits in the thalamus of major depressive disorder