title: Further evidence for the impact of a genome-wide-supported psychosis risk variant in ZNF804A on the Theory of Mind Network.
abstract: The single-nucleotide polymorphism (SNP) rs1344706 in ZNF804A is one of the best-supported risk variants for psychosis. We hypothesized that this SNP contributes to the development of schizophrenia by affecting the ability to understand other people's mental states. This skill, commonly referred to as Theory of Mind (ToM), has consistently been found to be impaired in schizophrenia. Using functional magnetic resonance imaging, we previously showed that in healthy individuals rs1344706 impacted on activity and connectivity of key areas of the ToM network, including the dorsomedial prefrontal cortex, temporo-parietal junction, and the posterior cingulate cortex, which show aberrant activity in schizophrenia patients, too. We aimed to replicate these results in an independent sample of 188 healthy German volunteers. In order to assess the reliability of brain activity elicited by the ToM task, 25 participants performed the task twice with an interval of 14 days showing excellent accordance in recruitment of key ToM areas. Confirming our previous results, we observed decreasing activity of the left temporo-parietal junction, dorsomedial prefrontal cortex, and the posterior cingulate cortex with increasing number of risk alleles during ToM. Complementing our replication sample with the discovery sample, analyzed in a previous report (total N=297), further revealed negative genotype effects in the left dorsomedial prefrontal cortex as well as in the temporal and parietal regions. In addition, as shown previously, rs1344706 risk allele dose positively predicted increased frontal-temporo-parietal connectivity. These findings confirm the effects of the psychosis risk variant in ZNF804A on the dysfunction of the ToM network.
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany [2] Mind and Brain Research Group, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mohnke
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany [2] Mind and Brain Research Group, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Erk
authors.affiliation: Department of Psychiatry, University of Heidelberg, Mannheim, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Schnell
authors.affiliation: Department of Psychiatry, University of Bonn, Bonn, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schütz
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany [2] Emotional Neuroscience Research Group, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Romanczuk-Seiferth
authors.affiliation: Department of Psychiatry, Central Institute of Mental Health, Mannheim, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Grimm
authors.affiliation: Department of Psychiatry, Central Institute of Mental Health, Mannheim, Germany.
authors.forename: Leila
authors.initials: L
authors.lastname: Haddad
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany [2] Emotional Neuroscience Research Group, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Pöhland
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany [2] Emotional Neuroscience Research Group, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Garbusow
authors.affiliation: Department of Psychiatry, University of Heidelberg, Mannheim, Germany.
authors.forename: Mike M
authors.initials: MM
authors.lastname: Schmitgen
authors.affiliation: Department of Psychology, Central Institute of Mental Health, Mannheim, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kirsch
authors.affiliation: Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Esslinger
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Witt
authors.affiliation: 1] Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany [2] Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: 1] Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany [2] Institute of Human Genetics, University of Bonn, Bonn, Germany [3] Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.affiliation: 1] Department of Psychiatry, University of Heidelberg, Mannheim, Germany [2] Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mattheisen
authors.affiliation: Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mühleisen
authors.affiliation: Centre for Psychology, University of Kristianstad, Kristianstad, Sweden.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Jensen
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany [2] Mind and Brain Research Group, Charité Universitätsmedizin Berlin, Berlin, Germany [3] Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany [4] Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors.forename: Björn H
authors.initials: BH
authors.lastname: Schott
authors.affiliation: Department of Psychiatry, University of Bonn, Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: Department of Psychiatry, Central Institute of Mental Health, Mannheim, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer-Lindenberg
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany [2] Mind and Brain Research Group, Charité Universitätsmedizin Berlin, Berlin, Germany [3] Department of Psychiatry, University of Bonn, Bonn, Germany [4] Berlin School of Mind and Brain, Humboldt University, Berlin, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Walter
mesh_terms: D000328:Adult; D000483:Alleles; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060005:Genotyping Techniques; D005858:Germany; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000235:genetics; D015203:Reproducibility of Results; D012307:Risk Factors; D013647:Task Performance and Analysis; D056345:Theory of Mind
chemical_list: D051741:Kruppel-Like Transcription Factors; C540527:ZNF804A protein, human