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Degeneration of dopaminergic circuitry influences depressive symptoms in Lewy body disorders.

Brain Pathology 2018 December 25
AIMS: Depression is commonly observed even in prodromal stages of Lewy body disorders (LBD), and is associated with cognitive impairment and a faster rate of cognitive decline. Given the role of dopamine in the development of movement disorders, but also in motivation and reward, we investigated neurodegenerative pathology in dopaminergic circuitry in Parkinson's disease (PD), PD with dementia (PDD) and dementia with Lewy bodies (DLB) patients in relation to depressive symptoms.

METHODS: α-synuclein, hyperphosphorylated tau and amyloid beta pathology was assessed in 17 DLB, 14 PDD and 8 PD cases within striatal and midbrain subregions, with neuronal cell density assessed in substantia nigra and ventral tegmental area. Additionally, we used a structural equation modelling (SEM) approach to investigate the extent to which brain connectivity might influence the deposition of pathological proteins within dopaminergic pathways.

RESULTS: A significantly higher α-synuclein burden was observed in the substantia nigra (p=0.006), ventral tegmental area (p=0.011) and nucleus accumbens (p=0.031) in LBD patients with depression. Significant negative correlations were observed between cell density in SN with LB Braak stage (p=0.013), whereas cell density in VTA showed negative correlations with LB Braak stage (p=0.026) and NFT Braak stage (p=0.007).

CONCLUSIONS: Dopaminergic α-syn pathology appears to drive depression. Selective targeting of dopaminergic pathways may therefore provide symptomatic relief for depressive symptoms in LBD patients. This article is protected by copyright. All rights reserved.

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