title: Elevated P3b latency variability in carriers of ZNF804A risk allele for psychosis.
abstract: Increased intra-subject variability (ISV) in reaction times (RTs) is a candidate endophenotype for several psychiatric and neurological conditions, including schizophrenia. ISV reflects the degree of variability in RTs and is thought to be an index of the stability of cognition. It is generally assumed to have the same underlying physiological basis across conditions, but recent evidence raises the possibility that the neural underpinnings of ISV vary with aetiology. Combining genetics with single-trial event-related potentials is an ideal method for investigating the neural basis of ISV in groups where ISV may vary for relatively homogenous reasons. Here we examine the association between P3b latency variability and a polymorphism on the ZNF804A gene associated with psychosis. Ninety-one healthy volunteers genotyped for rs1344706, a polymorphism on ZNF804A, had electroencephalographic data recorded while carrying out three n-back tasks. Data were analysed with a single-trial approach and latency variability of the P3b was compared between the AA homozygous risk group (N=30) and C allele carriers (N=61). P3b latencies were more variable for AA carriers than C carriers. Behavioural ISV, however, was not associated with genotype. The increase in neurophysiological variability, unaccompanied by increased behavioural variability, suggests that this risk gene is associated with an attenuated form of an endophenotype associated with the psychosis phenotype. The increase in both stimulus and response-locked variability also contrasts with previous work into attention-deficit hyperactivity disorder, where only response-locked P3b variability was elevated, suggesting that increased ISV may not signify the same underlying processes in all conditions with which it is associated.
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University of Freiburg, Hauptstrasse 8, Freiburg 79104, Germany; School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd LL57 2AS, UK.
authors.forename: Christopher W N
authors.initials: CW
authors.lastname: Saville
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Lancaster
authors.affiliation: School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd LL57 2AS, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Davies
authors.affiliation: School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd LL57 2AS, UK.
authors.forename: Maida
authors.initials: M
authors.lastname: Toumaian
authors.affiliation: School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd LL57 2AS, UK.
authors.forename: Eleni
authors.initials: E
authors.lastname: Pappa
authors.affiliation: School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd LL57 2AS, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Fish
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg, Hauptstrasse 5, 79104 Freiburg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Feige
authors.affiliation: Universitätsklinikum Frankfurt, Goethe University, Deutschordenstrasse, 50, Frankfurt am Main 60528, Germany; Child and Adolescent Psychiatry, University of Cologne, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bender
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK.
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Mantripragada
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK; School of Psychology, Cardiff University, Tower Building, 70 Park Place, Cardiff CF10 3AT, UK.
authors.forename: David 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 79104, Germany; School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd LL57 2AS, UK; Child and Adolescent Psychiatry, University of Cologne, Germany. Electronic address: christoph.klein.kjp@uniklinik-freiburg.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Klein
mesh_terms: D000328:Adult; D000483:Alleles; D002540:Cerebral Cortex / Q000502:physiology*; D004569:Electroencephalography; D018913:Event-Related Potentials, P300; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007206:Individuality; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D011597:Psychomotor Performance / Q000502:physiology*; D011618:Psychotic Disorders / Q000235:genetics*; D011930:Reaction Time; D012307:Risk Factors; D055815:Young Adult
chemical_list: D051741:Kruppel-Like Transcription Factors; C540527:ZNF804A protein, human