Left-right asymmetric and smaller right habenula volume in major depressive disorder on high-resolution 7-T magnetic resonance imaging

Abstract

The habenula (Hb) has been hypothesized to play an essential role in major depressive disorder (MDD) as it is considered to be an important node between fronto-limbic areas and midbrain monoaminergic structures based on animal studies. In this study, we aimed to investigate the differences in volume and T1 value of the Hb between patients with MDD and healthy control (HC) subjects. Analysis for the Hb volumes was performed using high-resolution 7-T magnetic resonance (MR) image data from 33 MDD patients and 36 healthy subjects. Two researchers blinded to the clinical data manually delineated the habenular nuclei and Hb volume, and T1 values were calculated based on overlapping voxels. We compared the Hb volume and T1 value between the MDD and HC groups and compared the volume and T1 values between the left and right Hbs in each group. Compared to HC subjects, MDD patients had a smaller right Hb volume; however, there was no significant volume difference in the left Hb between groups. In the MDD group, the right Hb was smaller in volume and lower in T1 value than the left Hb. The present findings suggest a smaller right Hb volume and left-right asymmetry of Hb volume in MDD. Future high-resolution 7-T MR imaging studies with larger sample sizes will be needed to derive a more definitive conclusion.

Fig 1

The habenula of an HC (left panel) and MDD patient (right panel). (a) axial MPRAGE, (b) axial view in ME-MP2RAGE T1 maps, and (c) coronal view in ME-MP2RAGE T1 maps. Compared to the surrounding tissues, the habenula has a brighter signal on the MPRAGE image and darker signal on the ME-MP2RAGE T1 map image. Overall, the contrast on the ME-MP2RAGE T1 map image is greater than that on the MPRAGE image. The yellow arrow points to the habenula, and the boundaries of the habenula are indicated by the yellow dotted line. Abbreviations: HC, healthy control; MDD, major depressive disorder; ME-MP2RAGE, multi-echo magnetization-prepared 2 rapid gradient echoes; MPRAGE, magnetization-prepared rapid gradient echo.

Fig 2

The right and left overlapping habenula in an (a) HC and (b) MDD patient on an axial ME-MP2RAGE T1 map segmented by Examiner #1 and Examiner #2. Red, blue, and green indicate the voxels segmented by Examiner #1, Examiner #2, and the overlap of voxels identified by both examiners, respectively. Abbreviations: R, right; L, left; HC, healthy control; MDD, major depressive disorder; ME-MP2RAGE, multi-echo magnetization-prepared 2 rapid gradient echoes.

Fig 3. Scatter plot with the mean and standard deviation of the volume and T1 value of the right and left habenula in each group.

Volumes or T1 value of the hemispheric habenula (Y axis) for the diagnostic groups (X axis). The graph plots the individual data points with a horizontal line superimposed at the mean and error bars showing plus and minus one SD of each group. We drew red lines between the combinations that differed significantly and marked them with an asterisk (*). Please note the smaller right habenula volume in the MDD group than the left habenula volume in the MDD group and those of the right and left habenula in HCs. Also, note that the T1 value in both the HC and MDD groups is lower in the right habenula than in the left. Abbreviations: Rt, right; Lt, left; HC, healthy control; MDD, major depressive disorder; SD, standard deviation.