title: Dopamine Gene Profiling to Predict Impulse Control and Effects of Dopamine Agonist Ropinirole.
abstract: Dopamine agonists can impair inhibitory control and cause impulse control disorders for those with Parkinson disease (PD), although mechanistically this is not well understood. In this study, we hypothesized that the extent of such drug effects on impulse control is related to specific dopamine gene polymorphisms. This double-blind, placebo-controlled study aimed to examine the effect of single doses of 0.5 and 1.0 mg of the dopamine agonist ropinirole on impulse control in healthy adults of typical age for PD onset. Impulse control was measured by stop signal RT on a response inhibition task and by an index of impulsive decision-making on the Balloon Analogue Risk Task. A dopamine genetic risk score quantified basal dopamine neurotransmission from the influence of five genes: catechol-O-methyltransferase, dopamine transporter, and those encoding receptors D1, D2, and D3. With placebo, impulse control was better for the high versus low genetic risk score groups. Ropinirole modulated impulse control in a manner dependent on genetic risk score. For the lower score group, both doses improved response inhibition (decreased stop signal RT) whereas the lower dose reduced impulsiveness in decision-making. Conversely, the higher score group showed a trend for worsened response inhibition on the lower dose whereas both doses increased impulsiveness in decision-making. The implications of the present findings are that genotyping can be used to predict impulse control and whether it will improve or worsen with the administration of dopamine agonists.
authors.affiliation: University of Auckland.
authors.forename: Hayley J
authors.initials: HJ
authors.lastname: MacDonald
authors.affiliation: University of Auckland.
authors.forename: Cathy M
authors.initials: CM
authors.lastname: Stinear
authors.affiliation: University of Auckland.
authors.forename: April
authors.initials: A
authors.lastname: Ren
authors.affiliation: Monash University, Melbourne, Australia.
authors.forename: James P
authors.initials: JP
authors.lastname: Coxon
authors.affiliation: Auckland District Health Board.
authors.forename: Justin
authors.initials: J
authors.lastname: Kao
authors.affiliation: Auckland District Health Board.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Macdonald
authors.affiliation: Auckland District Health Board.
authors.forename: Barry
authors.initials: B
authors.lastname: Snow
authors.affiliation: University of California, Irvine.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Cramer
authors.affiliation: University of Auckland.
authors.forename: Winston D
authors.initials: WD
authors.lastname: Byblow
mesh_terms: D000328:Adult; D000368:Aged; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003657:Decision Making / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007175:Impulsive Behavior / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D020641:Polymorphism, Single Nucleotide; D011930:Reaction Time / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050637:Receptors, Dopamine D3 / Q000235:genetics
chemical_list: C583260:DRD1 protein, human; C581293:DRD2 protein, human; C493593:DRD3 protein, human; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D007211:Indoles; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C046649:ropinirole; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase