Planning ability in Parkinson's disease is influenced by the COMT val158met polymorphism

Thomas Foltynie, Terry E. Goldberg, Simon G.J. Lewis, Andrew D. Blackwell, Bhaskar S. Kolachana, Daniel R. Weinberger, Trevor W. Robbins, Roger A. Barker

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


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 158met 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 158met 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.

Original languageEnglish (US)
Pages (from-to)885-891
Number of pages7
JournalMovement Disorders
Issue number8
StatePublished - Aug 2004
Externally publishedYes


  • COMT
  • Cognitive
  • Parkinson's disease
  • Phenotype
  • Polymorphism

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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