Special Theme: Catechol-O-Methyl Transferase (COMT), Recent Findings

Neuropsychopharmacology (2008) 33, 3046–3057; doi:10.1038/sj.npp.1301658; published online 30 January 2008

Catechol-O-Methyltransferase (COMT) Val158Met Genotype is Associated with BOLD Response as a Function of Task Characteristic

Ulrich Ettinger1, Veena Kumari2, David A Collier3,4, John Powell5, Sonija Luzi3, Tanja M Michel6, Olurotimi Zedomi1 and Steven C R Williams1

  1. 1King's College London, Centre for Neuroimaging Sciences, Institute of Psychiatry, London, UK
  2. 2King's College London, Department of Psychology, Institute of Psychiatry, London, UK
  3. 3King's College London, Division of Psychological Medicine, Institute of Psychiatry, London, UK
  4. 4King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK
  5. 5King's College London, Department of Neuroscience, Institute of Psychiatry, London, UK
  6. 6Department of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany

Correspondence: Dr U Ettinger, King's College London, Centre for Neuroimaging Sciences, Institute of Psychiatry, PO Box 89, De Crespigny Park, London SE5 8AF, UK. Tel: +44 20 3228 3057; Fax: +44 20 3228 2116; E-mail: u.ettinger@iop.kcl.ac.uk

Received 25 July 2007; Revised 24 October 2007; Accepted 13 November 2007; Published online 30 January 2008.

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Abstract

The catechol-O-methyltransferase (COMT) val158met single nucleotide polymorphism (rs4680) has been shown to be associated with brain activation during a number of neurocognitive and emotional tasks. The present study evaluated genotypic associations with brain function during measurement of cognitive stability (prosaccades) and plasticity (antisaccades). A total of 36 healthy volunteers were genotyped for rs4680 and underwent functional magnetic resonance imaging (fMRI) at 1.5T. Individuals with at least one val158 allele (val158 carriers, N=24) showed lower blood oxygen level-dependent (BOLD) response in ventromedial and dorsomedial prefrontal cortex during antisaccades compared to val158 noncarriers, whereas met158 homozygotes (N=12) showed lower BOLD response in a cluster in the posterior cingulate and precuneus during prosaccades compared to val158 carriers. These findings suggest that associations of COMT val158met genotype with brain function may be mediated by task characteristics. The findings may be compatible with a hypothesis on the role of COMT val158met genotype in tonic and phasic dopamine levels in brain and differential effects on cognitive measures of stability (eg prosaccades) and plasticity (eg antisaccades).

Keywords:

catechol-O-methyltransferase, fMRI, eye movements, endophenotype, genetics, dopamine

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