Thalamic white matter macrostructure and subnuclei volumes in Parkinson\u2019s disease depression

R Bhome,J H Cole,G E C Thomas,A Zarkali,R S Weil,J E Iglesias

doi:10.1038/s41531-021-00270-y

R Bhome, J H Cole + Show 4 more

Open Access

https://doi.org/10.1038/s41531-021-00270-y

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Abstract

Depression is a common non-motor feature of Parkinson’s disease (PD) which confers significant morbidity and is challenging to treat. The thalamus is a key component in the basal ganglia-thalamocortical network critical to the pathogenesis of PD and depression but the precise thalamic subnuclei involved in PD depression have not been identified. We performed structural and diffusion-weighted imaging (DWI) on 76 participants with PD to evaluate the relationship between PD depression and grey and white matter thalamic subnuclear changes. We used a thalamic segmentation method to divide the thalamus into its 50 constituent subnuclei (25 each hemisphere). Fixel-based analysis was used to calculate mean fibre cross-section (FC) for white matter tracts connected to each subnucleus. We assessed volume and FC at baseline and 14–20 months follow-up. A generalised linear mixed model was used to evaluate the relationship between depression, subnuclei volume and mean FC for each thalamic subnucleus. We found that depression scores in PD were associated with lower right pulvinar anterior (PuA) subnucleus volume. Antidepressant use was associated with higher right PuA volume suggesting a possible protective effect of treatment. After follow-up, depression scores were associated with reduced white matter tract macrostructure across almost all tracts connected to thalamic subnuclei. In conclusion, our work implicates the right PuA as a relevant neural structure in PD depression and future work should evaluate its potential as a therapeutic target for PD depression.

Highlights

Depression is a common neuropsychiatric feature of Parkinson’s disease (PD) with a prevalence of around 35%1
The PD group scored significantly lower than HC on Montreal Cognitive Assessment (MoCA) but the average score for both groups was within the normal range (≥26)
We found a significant association between Hospital Anxiety and Depression Scale (HADS) depression scores and fibre cross-section (FC) for tracts connected to all thalamic subnuclei apart

Summary

Introduction

Depression is a common neuropsychiatric feature of Parkinson’s disease (PD) with a prevalence of around 35%1. It is the key health-related determinant of poor quality of life in PD2. There is converging evidence to suggest that depression in PD arises primarily from the underlying neurobiology of the disorder rather than due to a psychological response to functional impairment. Depressive symptoms often arise in the prodromal stage prior to hallmark PD motor symptoms and genetic mutations linked to PD confer a risk of affective psychopathology[3,4]. A clear understanding of the neural correlates of PD depression has remained elusive, with functional, structural, and nuclear imaging studies yielding broad findings[5,6]. The frontotemporal regions, thalamus, amygdala, cerebellar white matter, hippocampus, nucleus accumbens, globus pallidus, anterior cingulate cortex and insula have all been implicated as potentially relevant brain regions and all three major monoaminergic systems are likely to be involved in the underlying pathophysiology[5,6]

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