Thalamic white matter macrostructure and subnuclei volumes in Parkinson’s disease depression

Objective Depression is a common non-motor feature of Parkinson9s disease (PD) which confers significant morbidity and is often challenging to treat. The thalamus is a key component in the basal ganglia-thalamocortical network critical to pathogenesis of PD and depression but the precise thalamic subnuclei involved in PD depression have not yet been identified and may even represent potential therapeutic targets. Methods We performed structural and diffusion weighted imaging 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). We used fixel based analysis of diffusion weighted imaging data to calculate mean fibre cross section (FC) for white matter tracts connected to each subnucleus and 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 of the 50 thalamic subnuclei, adjusting for age, gender, intracranial volume and time. Results 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 decreases in white matter tract macrostructure across almost all tracts connected to thalamic subnuclei. Conclusion We demonstrate that depression is associated with right thalamic PuA subnucleus volume loss and widespread thalamic white matter macrostructural changes, but that antidepressants may protect against volume loss in PD depression. Our work provides mechanistic insights for depression in PD, suggests possible benefits of actively treating depression, and a potential target for therapeutic intervention to the PuA subnucleus for PD depression.