Planning ability in Parkinson's disease is influenced by the COMT val158met polymorphism.
Parkinson's disease (PD) patients show a range of executive deficits involving dopaminergic transmission in the prefrontal cortex. In this study, we have investigated the impact of catechol-O-methyl-transferase (COMT) val(158)met polymorphisms on performance of the Tower of London (TOL) test of planning by PD patients. Motor and cognitive assessments were performed on 288 patients as part of a population-based study of PD. These patients were subsequently genotyped for the COMT val(158)met polymorphism. Patients with high activity COMT genotypes performed significantly better at the TOL task than those with low activity genotypes. Subgroup analyses suggest that this effect is greatest in patients exposed to dopaminergic agents. We hypothesise that the inferior performance in patients with the low activity COMT genotype is attributable to a state of relative hyperdopaminergic activity in the dorsolateral prefrontal cortex compared with that in the striatum. We suggest that polymorphisms of common genes, which regulate central nervous system dopaminergic transmission, can influence some of the phenotypic manifestations of PD.
Foltynie
Thomas
T
Cambridge Centre for Brain Repair, University of Cambridge, United Kingdom. tf210@medschl.cam.ac.uk
Goldberg
Terry E
TE
Lewis
Simon G J
SG
Blackwell
Andrew D
AD
Kolachana
Bhaskar S
BS
Weinberger
Daniel R
DR
Robbins
Trevor W
TW
Barker
Roger A
RA
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003210:Concept Formation / Q000502:physiology*; D003710:Demography; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D014633:Valine / Q000235:genetics
D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine