Journal Article

FZJ-2023-04810

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Impulsive-compulsive behaviour in early Parkinson’s disease is determined by apathy and dopamine receptor D3 polymorphism

Theis, H. ; Prange, S. ; Bischof, G. N.FZJ* ; Hoenig, M. C. ; Tittgemeyer, M. ; Timmermann, L. ; Fink, G. R.FZJ* ; Drzezga, A.FZJ* ; Eggers, C. ; van Eimeren, T. (Corresponding author)

2023
Nature Publ. Group London [u.a.]

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Please use a persistent id in citations: doi:10.1038/s41531-023-00596-9  doi:10.34734/FZJ-2023-04810

Abstract: Impulsive-compulsive behaviour (ICB) is a frequently observed non-motor symptom in early Parkinson’s disease after initiatingdopamine replacement therapy. At the opposite end of the motivated behaviour spectrum, apathy occurs in early Parkinson’sdisease even before dopamine replacement is started. The co-occurrence of these behavioural conditions in Parkinson’s diseaseraises questions about their relationship and underlying pathophysiological determinants. In previous imaging or genetic studies,both conditions have been associated with the limbic dopaminergic system. The risk variant of the Ser9Gly polymorphism of thedopamine receptor D3 (DRD3) is linked to increased dopamine affinity in the limbic striatum. With this in mind, we investigatedhow ICB expression is explained by apathy and DRD3 polymorphisms and their effects on grey matter volume and dopaminesynthesis capacity. Fifty-four patients with early Parkinson’s disease took part in anatomical T1-weighted MRI. Forty of them alsounderwent dynamic PET imaging using [18F]DOPA to measure striatal dopamine synthesis capacity. Further, Ser9Gly (rs6280) genepolymorphism influencing the DRD3 dopamine-binding affinity was determined in all patients. The severity of impulsivecompulsivebehaviour and apathy was assessed using the Questionnaire for Impulsive-Compulsive Disorders Rating Scale and theApathy Evaluation Scale. ICB and the severity of apathy were indeed positively correlated. Apathy and the DRD3 polymorphismwere interactive risk factors for ICB severity. Apathy was significantly linked to atrophy of the bilateral putamen. Patients with theDRD3 risk type had reduced dopamine synthesis capacity in the putamen and limbic striatum, apathy was associated with reduceddopamine synthesis capacity in the limbic striatum. The results of [18F]DOPA reached only trend significance. Apathy in drug-naïvePD patients might be a consequence of impaired striatal dopaminergic tone. This may represent a predisposing factor for thedevelopment of ICB after the initiation of dopamine replacement therapy. The risk type of DRD3 could further amplify thispredisposition due to its higher affinity to dopamine.

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Contributing Institute(s):

1. Kognitive Neurowissenschaften (INM-3)
2. Molekulare Organisation des Gehirns (INM-2)

Research Program(s):

1. 5251 - Multilevel Brain Organization and Variability (POF4-525) (POF4-525)
2. DFG project 431549029 - SFB 1451: Schlüsselmechanismen normaler und krankheitsbedingt gestörter motorischer Kontrolle (431549029) (431549029)
3. DFG project 491111487 - Open-Access-Publikationskosten / 2022 - 2024 / Forschungszentrum Jülich (OAPKFZJ) (491111487) (491111487)
4. 5252 - Brain Dysfunction and Plasticity (POF4-525) (POF4-525)
5. 5253 - Neuroimaging (POF4-525) (POF4-525)

Appears in the scientific report 2023

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