Martini, A ORCID: 0000-0002-6349-0831, Dal Lago, D, Edelstyn, N, Salgarello, M, Lugoboni, F and Tamburin, S (2018) Dopaminergic neurotransmission in patients with Parkinson’s disease and impulse control disorders: a systematic review and meta-analysis of PET and SPECT studies. Frontiers in Neurology. ISSN 1664-2295

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Abstract

Background
Around 30% Parkinson’s disease (PD) patients develop impulse control disorders (ICDs) to D2/3 dopamine agonists and, to a lesser extent, levodopa. We aim to investigate striatal dopaminergic function in PD patients with and without ICD.

Methods
PubMed, Science Direct, EBSCO, and ISI Web of Science databases were searched (from inception to March 7, 2018) to identify PET or SPECT studies reporting striatal dopaminergic function in PD patients with ICD (ICD+) compared to those without ICD (ICD-). Studies which included drug naïve patients, explored non-pharmacological procedures (e.g., deep brain stimulation), and those using brain blood perfusion or non-dopaminergic markers were excluded. Standardized mean difference (SDM) was used and random-effect models were applied. Separate meta-analyses were performed for dopamine transporter level, dopamine release, and dopamine receptors availability in the putamen, caudate, dorsal and ventral striatum.

Results
A total of 238 studies were title and abstract screened, of which 19 full-texts were assessed. Nine studies (ICD+: N=117; ICD-: N=175 patients) were included in the analysis. ICD+ showed a significant reduction of dopamine transporter binding in the putamen (SDM=-0.46; 95% CI: -0.80, -0.11; Z= 2.61; p=0.009), caudate (SDM=-0.38; 95% CI: -0.73, -0.04; Z= 2.18; p=0.03) and dorsal striatum (SDM=-0.45; 95% CI: -0.77, -0.13; Z= 2.76; p=0.006), and increased dopamine release to reward-related stimuli/gambling tasks in the ventral striatum (SDM=-1.04; 95% CI: -1.73, -0.35; Z= 2.95; p=0.003). Dopamine receptors availability did not differ between groups. Heterogeneity was low for dopamine transporter in the dorsal striatum (I2=0%), putamen (I2=0%) and caudate (I2=0%), and pre-synaptic dopamine release in the dorsal (I2=0%) and ventral striatum (I2=0%); heterogeneity was high for dopamine transporter levels in the ventral striatum (I2=80%), and for dopamine receptors availability in the ventral (I2=89%) and dorsal (I2=86%) striatum, putamen (I2=93%), and caudate (I2=71%).

Conclusions
ICD+ patients show lower dopaminergic transporter levels in the dorsal striatum and increased dopamine release in the ventral striatum when engaged in reward-related stimuli/gambling tasks. This dopaminergic imbalance might represent a biological substrate for ICD in PD. Adequately powered longitudinal studies with drug naïve patients are needed to understand whether these changes may represent biomarkers of premorbid vulnerability to ICD.

Item Type: Article
Additional Information: This is the final published version of the article (version of record). It first appeared online via Frontiers Media at http://doi.org/10.3389/fneur.2018.01018 - please refer to any applicable terms of use of the publisher.
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > R Medicine (General)
Divisions: Faculty of Natural Sciences > School of Psychology
Depositing User: Symplectic
Date Deposited: 12 Nov 2018 09:21
Last Modified: 10 Dec 2018 09:03
URI: http://eprints.keele.ac.uk/id/eprint/5494

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