Microstructural deficits of the thalamus in major depressive disorder

Macroscopic structural abnormalities in the thalamus and thalamic circuits have been implicated in the neuropathology of major depressive disorder. However, cytoarchitectonic properties underlying these macroscopic abnormalities remain unknown. Here, we examined 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 MRI was used to examine structural-related alternations in 56 patients with depression compared with 35 age- and sex-matched controls. The seed-based probabilistic tractography showed multiple alterations of structural connectivity within a set of subcortical areas and their connections to cortical regions in patients with depression. These subcortical regions included the putamen, thalamus and caudate, which are predominantly involved in the limbic-cortical-striatal-pallidal-thalamic network. Structural connectivity was disrupted within and between large-scale networks, including the subcortical network, default-mode network and salience network. Consistently, morphometric measurements, including cortical thickness and voxel-based morphometry, showed widespread volume reductions of these key regions in patients with depression. A conjunction analysis identified common structural alternations of the left orbitofrontal cortex, left putamen, bilateral thalamus and right amygdala across macro-modalities. Importantly, the microstructural properties, longitudinal relaxation time of the left thalamus was increased and inversely correlated with its grey matter volume in patients with depression. Together, this work to date provides the first macro-micro neuroimaging evidence for the structural abnormalities of the thalamus in patients with depression, shedding light on the neuropathological disruptions of the limbic-cortical-striatal-pallidal-thalamic circuit in major depressive disorder. These findings have implications in understanding the abnormal changes of brain structures across the development of depression.