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Degeneration of dopaminergic circuitry influences depressive symptoms in Lewy body disorders

Lookup NU author(s): Lina Patterson, Professor Stephen Rushton, Professor Johannes Attems, Professor Alan Thomas, Dr Christopher Morris

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© 2018 The Authors Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology 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 modeling (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 substantia nigra with Lewy body (LB) Braak stage (P = 0.013), whereas cell density in ventral tegmental area showed negative correlations with LB Braak stage (P = 0.026) and neurofibrillary tangle Braak stage (P = 0.007). Conclusions: Dopaminergic α-synuclein pathology appears to drive depression. Selective targeting of dopaminergic pathways may therefore provide symptomatic relief for depressive symptoms in LBD patients.


Publication metadata

Author(s): Patterson L, Rushton SP, Attems J, Thomas AJ, Morris CM

Publication type: Article

Publication status: Published

Journal: Brain Pathology

Year: 2019

Volume: 29

Issue: 4

Pages: 544-557

Print publication date: 01/07/2019

Online publication date: 24/12/2018

Acceptance date: 06/12/2018

Date deposited: 15/02/2019

ISSN (print): 1015-6305

ISSN (electronic): 1750-3639

Publisher: Wiley-Blackwell

URL: https://doi.org/10.1111/bpa.12697

DOI: 10.1111/bpa.12697


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