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Motor impulsivity in Parkinson disease: associations with COMT and DRD2 polymorphisms
David A Ziegler1, Paymon Ashourian, Julien S Wonderlick
1Department of Neurology and the Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, CA, USA; Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Scandinavian Journal of Psychology
|April 23, 2014
Summary
Genetic variations in the COMT gene increase motor impulsivity in Parkinson disease (PD) patients undergoing dopamine replacement therapy. DRD2 gene variations did not show a significant link to impulsivity in PD patients.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Parkinson disease (PD) is a neurodegenerative disorder affecting motor, cognitive, and psychiatric functions.
- Dopaminergic medications, while crucial for motor symptom management in PD, can lead to side effects like hallucinations and impulse control disorders.
- Individual genetic differences in the dopamine system may influence patient response to dopaminergic therapy.
Purpose of the Study:
- To investigate the hypothesis that specific genetic variations (alleles) influencing dopamine signaling increase motor impulsivity in PD patients on dopamine replacement therapy.
- To examine the relationship between inhibitory control, measured by the Stop Signal Task, and polymorphisms in the COMT Val158Met and DRD2 C957T genes in idiopathic PD patients.
Main Methods:
- Assessed inhibitory ability using the Stop Signal Task in patients with idiopathic Parkinson disease.
- Genotyped patients for COMT Val158Met and DRD2 C957T polymorphisms.
- Correlated genetic variations with performance on the Stop Signal Task to measure motor impulsivity.
Main Results:
- Carriers of the COMT Val/Met and Met/Met genotypes exhibited significantly higher impulsivity on the Stop Signal Task compared to Val/Val carriers.
- No significant association was found between DRD2 C957T polymorphisms and inhibitory ability in PD patients.
- The Met allele of COMT was linked to increased risk of behavioral impulsivity in PD patients receiving dopaminergic therapy.
Conclusions:
- The COMT Val158Met polymorphism, specifically the Met allele, is associated with increased motor impulsivity in Parkinson disease patients treated with dopamine replacement therapy.
- DRD2 polymorphisms appear to play a less significant role in mediating medication-induced motor impulsivity in PD.
- These findings highlight the role of genetic factors in predicting adverse behavioral effects of dopaminergic treatment in PD.
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