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Front. Neurol. | doi: 10.3389/fneur.2018.00109

Dopaminergic and Opioid Pathways Associated with Impulse Control Disorders in Parkinson’s disease

 Aleksander H. Erga1*, Ingvild Dalen2,  Anastasia Ushakova2,  Janete Chung1, Charalampos Tzoulis3, 4, Ole-Bjørn Tysnes3, 4, Guido W. Alves1, 5, 6, Kenn F. Pedersen1, 5 and  Jodi M. Grødem1, 7
  • 1Stavanger University Hospital, Norwegian Centre for Movement Disorders, Stavanger University Hospital, Norway
  • 2Department of Research, Stavanger University Hospital, Norway
  • 3Department of Neurology, Haukeland University Hospital, Norway
  • 4Department of Clinical Medicine, University of Bergen, Norway
  • 5Department of Neurology, Stavanger University Hospital, Norway
  • 6Department of Mathematics and Natural Sciences, University of Stavanger, Norway
  • 7The Centre for Organelle Research, University of Stavanger, Norway

Impulse control disorders (ICDs) are frequent non-motor symptoms in Parkinson’s disease (PD), with potential negative effects on quality of life and social functioning. ICDs are closely associated with dopaminergic therapy, and genetic polymorphisms in several neurotransmitter pathways may increase the risk of addictive behaviors in PD. However, clinical differentiation between patients at risk and patients without risk of ICDs is still troublesome. The aim of this study was to investigate if genetic polymorphisms across several neurotransmitter pathways are associated with ICD status in patients with PD.

Methods: Whole exome sequencing data was available for 119 eligible PD patients from the Norwegian ParkWest study. All participants underwent comprehensive neurological, neuropsychiatric and neuropsychological assessments. ICDs were assessed using the self-report short form version of the Questionnaire for Impulsive-Compulsive Disorders in PD. Single nucleotide polymorphisms (SNPs) from 17 genes were subjected to regression with elastic net-penalization to identify candidate variants associated with ICDs. The area under the curve of receiver operating characteristic curves was used to evaluate the level of ICD prediction.

Results: Among the 119 patients with PD included in the analysis, 29% met the criteria for ICD and 63% were using dopamine agonists. Eleven SNPs were associated with ICDs, and the four SNPs with the most robust performance significantly increased ICD predictability (AUC = 0.81, 95% CI 0.73-0.90) compared to clinical data alone (dopamine agonist use and age; AUC = 0.65, 95% CI 0.59-0.78). The strongest predictive factors were rs5326 in DRD1, which was associated with increased odds of ICDs, and rs702764 in OPRK1, which was associated with decreased odds of ICDs.

Conclusions: Using an advanced statistical approach, we identified SNPs in nine genes, including a novel polymorphism in DRD1, with potential application for identification of PD patients at risk for ICDs.

Keywords: Parkinson Disease, Impulse Control Disorders, Addiction, elastic net, OPRK1, DRD1

Received: 21 Nov 2017; Accepted: 14 Feb 2018.

Edited by:

Mayela Rodríguez-Violante, Instituto Nacional de Neurología y Neurocirugía (INNN), Mexico

Reviewed by:

Félix Javier Jiménez-Jiménez, Hospital Universitario del Sureste, Spain
Daniel Martinez-Ramirez, University of Florida, United States  

Copyright: © 2018 Erga, Dalen, Ushakova, Chung, Tzoulis, Tysnes, Alves, Pedersen and Grødem. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mr. Aleksander H. Erga, Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger University Hospital, PB 8100, Stavanger, 4068, Norway,