title: COMT Val158Met genotype is associated with fluctuations in working memory performance: converging evidence from behavioural and single-trial P3b measures.
abstract: Intra-subject variability in reaction times (ISV) is a promising endophenotype for several psychiatric conditions, but its neural underpinnings are not yet established. Converging evidence from neuroimaging, molecular genetics, and psychopharmacology suggests that ISV could index catecholaminergically-mediated neural noise. The fine-grained temporal resolution of electroencephalography is ideal for investigating ISV, but only if potential neural correlates of ISV can be assessed in single trials. Based on evidence that ISV is associated with dopaminergic functioning, we apply a recently developed method of single-trial P3b analysis to investigate the association of COMT Val(158)Met genotype with measures of ISV on the behavioural and neural levels at different working memory loads. Greater number of Met alleles was associated with poorer and more intra-individually variable performance on the tasks, and greater latency jitter in single-trial P3bs. These converging results at the behavioural and neurophysiological levels confirm previous observations that prefrontal dopamine availability is associated with stability and accuracy of cognitive performance. Together with previous studies, these data imply pleiotropic cognitive effects of COMT genotype.
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University of Freiburg, Hauptstrasse 8, Freiburg, Germany, 79104; School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd, United Kingdom, LL57 2AS.
authors.forename: C W N
authors.initials: CW
authors.lastname: Saville
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff, United Kingdom, CF14 4XN.
authors.forename: T M
authors.initials: TM
authors.lastname: Lancaster
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University of Freiburg, Hauptstrasse 8, Freiburg, Germany, 79104; School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd, United Kingdom, LL57 2AS.
authors.forename: M E
authors.initials: ME
authors.lastname: Stefanou
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University of Freiburg, Hauptstrasse 8, Freiburg, Germany, 79104; School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd, United Kingdom, LL57 2AS.
authors.forename: G
authors.initials: G
authors.lastname: Salunkhe
authors.affiliation: School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd, United Kingdom, LL57 2AS.
authors.forename: I
authors.initials: I
authors.lastname: Lourmpa
authors.affiliation: School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd, United Kingdom, LL57 2AS.
authors.forename: A
authors.initials: A
authors.lastname: Nadkarni
authors.affiliation: School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd, United Kingdom, LL57 2AS.
authors.forename: S G
authors.initials: SG
authors.lastname: Boehm
authors.affiliation: Universitätsklinikum Frankfurt, Goethe University, Deutschordenstrasse, 50, Frankfurt am Main, Germany, 60528.
authors.forename: S
authors.initials: S
authors.lastname: Bender
authors.affiliation: Department of Psychiatry, National and Kapodistrian University of Athens, Eginition Hospital, 74 Vassilisis Sofias Avenue, Athens, Greece, 11528.
authors.forename: N
authors.initials: N
authors.lastname: Smyrnis
authors.affiliation: Department of Psychology, University of Bonn, Kaiser-Karl-Ring 9, Bonn, Germany 53111.
authors.forename: U
authors.initials: U
authors.lastname: Ettinger
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg, Hauptstrasse 5, Freiburg, Germany, 79104.
authors.forename: B
authors.initials: B
authors.lastname: Feige
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University of Freiburg, Hauptstrasse 8, Freiburg, Germany, 79104.
authors.forename: M
authors.initials: M
authors.lastname: Biscaldi
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff, United Kingdom, CF14 4XN.
authors.forename: K K
authors.initials: KK
authors.lastname: Mantripragada
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff, United Kingdom, CF14 4XN.
authors.forename: D E J
authors.initials: DE
authors.lastname: Linden
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University of Freiburg, Hauptstrasse 8, Freiburg, Germany, 79104; School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd, United Kingdom, LL57 2AS. Electronic address: c.klein@bangor.ac.uk.
authors.forename: C
authors.initials: C
authors.lastname: Klein
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004569:Electroencephalography; D018913:Event-Related Potentials, P300 / Q000502:physiology*; D005260:Female; D058685:Genetic Pleiotropy / Q000235:genetics / Q000502:physiology; D006801:Humans; D007206:Individuality; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology*; D055815:Young Adult
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Endophenotype; Intra-subject variability; Mental chronometry; P300; Reaction time variability; rs4680