The volumetric and shape changes of the putamen and thalamus in first episode, untreated major depressive disorder

Abstract

Previous MRI studies confirmed abnormalities in the limbic-cortical-striatal-pallidal-thalamic (LCSPT) network or limbic-cortico-striatal-thalamic-cortical (LCSTC) circuits in patients with major depressive disorder (MDD), but few studies have investigated the subcortical structural abnormalities. Therefore, we sought to determine whether focal subcortical grey matter (GM) changes might be present in MDD at an early stage. We recruited 30 first episode, untreated patients with major depressive disorder (MDD) and 26 healthy control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetric and shape analyses were used to assess volume and shape changes of the subcortical GM structures, respectively. In addition, probabilistic tractography methods were used to demonstrate the relationship between the subcortical and the cortical GM. Compared to healthy controls, MDD patients had significant volume reductions in the bilateral putamen and left thalamus (FWE-corrected, p < 0.05). Meanwhile, the vertex-based shape analysis showed regionally contracted areas on the dorsolateral and ventromedial aspects of the bilateral putamen, and on the dorsal and ventral aspects of left thalamus in MDD patients (FWE-corrected, p < 0.05). Additionally, a negative correlation was found between local atrophy in the dorsal aspects of the left thalamus and clinical variables representing severity. Furthermore, probabilistic tractography demonstrated that the area of shape deformation of the bilateral putamen and left thalamus have connections with the frontal and temporal lobes, which were found to be related to major depression. Our results suggested that structural abnormalities in the putamen and thalamus might be present in the early stages of MDD, which support the role of subcortical structure in the pathophysiology of MDD. Meanwhile, the present study showed that these subcortical structural abnormalities might be the potential trait markers of MDD.

Keywords: Major depressive disorder; Putamen; Shape analysis; Thalamus; Volumetric analysis.

Supplementary Fig. 1

Vertex-wise comparison on the other subcortical gray matter between MDD patients and HCs.

Supplementary Fig. 2

Vertex-wise correlation of HRDS scores with regional shape deformation on the other subcortical gray matter in MDD patients.

Fig. 1

Vertex-wise comparison shows significant regional shape deformation on the dorsolateral and ventromedial aspects of the bilateral putamen Panel a, left putamen; Panel b, right putamen) and the dorsal and ventral aspects of the left thalamus Panel c in MDD patients, compared to HCs (family wise error-corrected, p < 0.05).

Fig. 2

Vertex-wise comparison shows a significant negative correlation of HRDS scores with regional shape deformation on the dorsal side of the left thalamus in MDD patients (FWE-corrected, p < 0.05).

Fig. 3

Probabilistic tractography shows the mean tracts originating from the area of shape difference in the bilateral putamen. The yellow part is the putamen structure and the red part is the area of shape deformation. The green part is the fibre bundle, which was generated from the area of shape deformation. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Probabilistic tractography shows the mean tracts originating from the area of shape difference in the left thalamus (Fig 4). The blue part is the thalamus structure and the red part is the area of shape deformation. The green part is the fibre bundle, which was generated from the area of shape deformation. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 5

Probabilistic tractography shows the mean tracts originating from the shape deformation area in the dorsal aspects of the left thalamus, which have a significant negative correlation with HRDS scores. The blue part is the thalamus structure. The red part is the area of shape deformation; the green part is the fibre bundle, which was generated from the area of shape deformation. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)