title: Motor impulsivity in Parkinson disease: associations with COMT and DRD2 polymorphisms.
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.
authors.affiliation: Department 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.
authors.forename: David A
authors.initials: DA
authors.lastname: Ziegler
authors.forename: Paymon
authors.initials: P
authors.lastname: Ashourian
authors.forename: Julien S
authors.initials: JS
authors.lastname: Wonderlick
authors.forename: Alison K
authors.initials: AK
authors.lastname: Sarokhan
authors.forename: Drazen
authors.initials: D
authors.lastname: Prelec
authors.forename: Clemens R
authors.initials: CR
authors.lastname: Scherzer
authors.forename: Suzanne
authors.initials: S
authors.lastname: Corkin
mesh_terms: D000368:Aged; D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000502:physiology*; D007266:Inhibition, Psychological; D008297:Male; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology*; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics*
chemical_list: C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: COMT; Parkinson disease; dopamine; impulse control disorder
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