Motor impulsivity in Parkinson disease: Associations with COMT and DRD2 polymorphisms

Authors

  • David A. Ziegler,

    Corresponding author
    1. Department of Neurology and the Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, CA, USA
    2. Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA
    • David A. Ziegler, University of California, San Francisco, Sandler Neurosciences Center, 675 Nelson Rising Lane, UCSF MC 0444, San Francisco, CA 94158, USA. Tel: 415-502-7322; e-mail: david@gazzaleylab.ucsf.edu

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  • Paymon Ashourian,

    1. Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA
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  • Julien S. Wonderlick,

    1. Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA
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  • Alison K. Sarokhan,

    1. The Neurogenomics Laboratory, Harvard Medical School and Brigham & Women's Hospital, Cambridge, MA, USA
    2. Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA, USA
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  • Drazen Prelec,

    1. Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA
    2. Sloan School and Neuroeconomics Center, Department of Economics, Massachusetts Institute of Technology, Cambridge, MA, USA
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  • Clemens R. Scherzer,

    1. The Neurogenomics Laboratory, Harvard Medical School and Brigham & Women's Hospital, Cambridge, MA, USA
    2. Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA, USA
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  • Suzanne Corkin

    1. Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA
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Abstract

Parkinson disease (PD) is an age-related degenerative disease of the brain, characterized by motor, cognitive, and psychiatric symptoms. Neurologists and neuroscientists now understand that several symptoms of the disease, including hallucinations and impulse control behaviors, stem from the dopaminergic medications used to control the motor aspects of PD. Converging evidence from animals and humans suggests that individual differences in the genes that affect the dopamine system influence the response of PD patients to dopaminergic medication. In this study, we tested the hypothesis that patients taking dopamine replacement therapy who carry candidate alleles that increase dopamine signaling, exhibit greater amounts of motor impulsivity. We examined the relation between inhibitory ability (measured by the Stop Signal Task) and polymorphisms of COMT Val158Met and DRD2 C957T in patients with idiopathic PD. On the Stop Signal Task, carriers of COMT Val/Met and Met/Met genotypes were more impulsive than Val/Val carriers, but we did not find a link between DRD2 polymorphisms and inhibitory ability. These results support the hypothesis that the Met allele of COMT confers an increased risk for behavioral impulsivity in PD patients, whereas DRD2 polymorphisms appear to be less important in determining whether PD patients exhibit a dopamine overdose in the form of motor impulsivity.

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