title: Dopaminergic influences on executive function and impulsive behaviour in impulse control disorders in Parkinson's disease.
abstract: The development of impulse control disorders (ICDs) in Parkinson's disease (PD) may arise from an interaction among cognitive impairment, impulsive responding and dopaminergic state. Dopaminergic state may be influenced by pharmacologic or genotypic (catechol-O-methyltransferase; COMT) factors. We sought to investigate this interaction further by comparing those with (n = 35) and without (n = 55) ICDs on delay-discounting in different pharmacologic conditions (ON or OFF dopaminergic medication) and on response inhibition as well as aspects of executive functioning in the ON state. We then undertook an exploratory sub-group analysis of these same tasks when the overall PD group was divided into different allelic variants of COMT (val/val vs. met/met). A healthy control group (HC; n = 20) was also included. We found that in those with PD and ICDs, 'cognitive flexibility' (set shifting, verbal fluency, and attention) in the ON medication state was not impaired compared with those without ICDs. In contrast, our working memory, or 'cognitive focus', task was impaired in both PD groups compared with the HC group when ON. During the delay-discounting task, the PD with ICDs group expressed greater impulsive choice compared with the PD group without ICDs, when in the ON, but not the OFF, medication state. However, no group difference on the response inhibition task was seen when ON. Finally, the met homozygous group performed differently on tests of executive function compared with the val homozygous group. We concluded that the disparity in levels of impairment among different domains of executive function and impulsive decision-making distinguishes those with ICD in PD from those without ICD, and may in part be affected by dopaminergic status. Both pharmacologic and genotypic influences on dopaminergic state may be important in ICD.
authors.affiliation: Institute of Brain, Behaviour and Mental Health, University of Manchester, UK; Manchester Mental Health and Social Care Trust, Manchester, UK. Iracema.leroi@manchester.ac.uk
authors.forename: Iracema
authors.initials: I
authors.lastname: Leroi
authors.forename: Michelle
authors.initials: M
authors.lastname: Barraclough
authors.forename: Shane
authors.initials: S
authors.lastname: McKie
authors.forename: Neal
authors.initials: N
authors.lastname: Hinvest
authors.forename: Jonathan
authors.initials: J
authors.lastname: Evans
authors.forename: Rebecca
authors.initials: R
authors.lastname: Elliott
authors.forename: Kathryn
authors.initials: K
authors.lastname: McDonald
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000523:psychology*; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D056344:Executive Function / Q000187:drug effects*; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000139:chemically induced / Q000235:genetics / Q000523:psychology*; D007266:Inhibition, Psychological; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000523:psychology*
chemical_list: D018491:Dopamine Agonists; D002394:Catechol O-Methyltransferase