title: Influence of COMT genotype and affective distractors on the processing of self-generated thought.
abstract: The catechol-O-methyltransferase (COMT) enzyme is a major determinant of prefrontal dopamine levels. The Val(158)Met polymorphism affects COMT enzymatic activity and has been associated with variation in executive function and affective processing. This study investigated the effect of COMT genotype on the flexible modulation of the balance between processing self-generated and processing stimulus-oriented information, in the presence or absence of affective distractors. Analyses included 124 healthy adult participants, who were also assessed on standard working memory (WM) tasks. Relative to Val carriers, Met homozygotes made fewer errors when selecting and manipulating self-generated thoughts. This effect was partly accounted for by an association between COMT genotype and visuospatial WM performance. We also observed a complex interaction between the influence of affective distractors, COMT genotype and sex on task accuracy: male, but not female, participants showed a sensitivity to the affective distractors that was dependent on COMT genotype. This was not accounted for by WM performance. This study provides novel evidence of the role of dopaminergic genetic variation on the ability to select and manipulate self-generated thoughts. The results also suggest sexually dimorphic effects of COMT genotype on the influence of affective distractors on executive function.
authors.affiliation: Institute of Cognitive Neuroscience, University College London, 17 Queen Square, London, WC1N 3AR, UK, Department of Psychological Sciences, Birkbeck, University of London, Malet Street, London, WC1E 7HX, UK and Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK e.kilford.12@ucl.ac.uk.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Kilford
authors.affiliation: Institute of Cognitive Neuroscience, University College London, 17 Queen Square, London, WC1N 3AR, UK, Department of Psychological Sciences, Birkbeck, University of London, Malet Street, London, WC1E 7HX, UK and Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK Institute of Cognitive Neuroscience, University College London, 17 Queen Square, London, WC1N 3AR, UK, Department of Psychological Sciences, Birkbeck, University of London, Malet Street, London, WC1E 7HX, UK and Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
authors.forename: Iroise
authors.initials: I
authors.lastname: Dumontheil
authors.affiliation: Institute of Cognitive Neuroscience, University College London, 17 Queen Square, London, WC1N 3AR, UK, Department of Psychological Sciences, Birkbeck, University of London, Malet Street, London, WC1E 7HX, UK and Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.affiliation: Institute of Cognitive Neuroscience, University College London, 17 Queen Square, London, WC1N 3AR, UK, Department of Psychological Sciences, Birkbeck, University of London, Malet Street, London, WC1E 7HX, UK and Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
authors.forename: Sarah-Jayne
authors.initials: SJ
authors.lastname: Blakemore
mesh_terms: D000328:Adult; D000339:Affect / Q000502:physiology*; D001288:Attention / Q000502:physiology*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D056344:Executive Function / Q000502:physiology; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D013850:Thinking / Q000502:physiology*; D055815:Young Adult
chemical_list: D002394:Catechol O-Methyltransferase
keywords: COMT; affective processing; behavioural genetics; executive function; prefrontal cortex