Objective: To assess whether dysregulation of habenula (Hb) contributes to mood disorders in Parkinson’s disease (PD).

Background: PD is often accompanied by mood disorders, such as depression, anxiety, apathy, and impulse control disorders (1,2). The Hb, which is the anti-reward center of the brain, is found to be crucial in the pathophysiology of depression (3,4). Hb dysfunction may be critical for PD-related mood disorders.

Method: 105 PD and 45 healthy controls (HC) were recruited from Maastricht University Medical Centre. The participants with clinical depression were excluded. Beck Depression Inventory (BDI) was used to assess depression. A 7T brain MRI was conducted. Hb was manually segmented from the 3D MPRAGE images using ITK-SNAP version 3.8.0.

Results: BDI total scores were significantly higher in PD group. Mean total Hb and right Hb volumes were significantly bigger in PD group (p=0.046, and p=0.032, respectively). Left Hb volume was significantly bigger than right in both PD and HC groups.

When the PD and HC groups were divided into the subgroups according to BDI total scores as with and without depression, there were no volumetric differences between PD subgroups (p=0.842 for left, p=0.566 for right), and also HC subgroups (p=0.517 for left, p=0.590 for right). There were no correlations between Hb volumes with BDI scores.

Conclusion: This is the first study in which the volume of Hb in relation to mood disorders in PD was examined with 7T MRI. Increased mean total Hb and right Hb volumes in PD patients may be associated with not having any PD patients with clinical depression in this study. It was already reported that the first episode or subclinical depression might be related to bigger habenula volumes, and the volumes could decrease with chronic or treatment-resistant depression (5). Right Hb is also known to have more connections with substantia nigra and ventral tegmental area than the left, and increased volume may also be related to motor symptoms in PD.

References: 1. Cummings JL, Masterman DL. Depression in patients with Parkinson’s disease. Int J Geriatr Psychiatry. 1999;14(9):711-8.
2. Kano O, Ikeda K, Cridebring D, Takazawa T, Yoshii Y, Iwasaki Y. Neurobiology of depression and anxiety in Parkinson’s disease. Parkinsons Dis. 2011;2011:143547.
3. Li B, Piriz J, Mirrione M, Chung C, Proulx CD, Schulz D, et al. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. Nature. 2011;470(7335):535-9.
4. Proulx CD, Hikosaka O, Malinow R. Reward processing by the lateral habenula in normal and depressive behaviors. Nat Neurosci. 2014;17(9):1146-52.
5. Cho SE, Park CA, Na KS, Chung C, Ma HJ, Kang CK, Kang SG. Left-right asymmetric and smaller right habenula volume in major depressive disorder on high-resolution 7-T magnetic resonance imaging. PLoS One. 2021 Aug 3;16(8):e0255459.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/habenula-volume-in-mood-disorders-in-parkinsons-disease/