title: Alterations in neural Theory of Mind processing in euthymic patients with bipolar disorder and unaffected relatives.
abstract: OBJECTIVE
  Behavioral deficits in the Theory of Mind (ToM) have been robustly demonstrated in bipolar disorder. These deficits may represent an intermediate phenotype of the disease. The aim of this study was: (i) to investigate alterations in neural ToM processing in euthymic patients with bipolar disorder, and (ii) to examine whether similar effects are present in unaffected relatives of patients with bipolar disorder suggesting that ToM functional activation may be, in part, due to genetic risk for the disease.
  
  
  METHODS
  A total of 24 euthymic patients with bipolar disorder, 21 unaffected first-degree relatives, and 81 healthy controls completed a ToM task while undergoing functional magnetic resonance imaging.
  
  
  RESULTS
  We observed reduced bilateral activation of the temporoparietal junction (TPJ) and diminished functional fronto-temporoparietal connectivity in patients compared to controls. Relatives tended towards intermediate temporoparietal activity and functional coupling with medial prefrontal areas. There was also evidence for a potentially compensatory enhanced recruitment of the right middle temporal gyrus and stronger connectivity between this region and the medial prefrontal cortex in relatives.
  
  
  CONCLUSIONS
  These findings provide further evidence of altered neural ToM processing in euthymic patients with bipolar disorder. Further, our findings in relatives lend support to the idea that altered ToM processing may act as an intermediate phenotype of the disorder.
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Willert
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Sebastian
authors.identifier: http://orcid.org/0000-0002-9177-6394
authors.initials: S
authors.lastname: Mohnke
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Erk
authors.affiliation: Department of Psychiatry, University of Heidelberg, Heidelberg, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Schnell
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Romanczuk-Seiferth
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Quinlivan
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schreiter
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Spengler
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Dorrit
authors.initials: D
authors.lastname: Herold
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Wackerhagen
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Romund
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Garbusow
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Tristram
authors.initials: T
authors.lastname: Lett
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stamm
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.|Fliedner Klinik Berlin, Berlin, Germany.
authors.forename: Mazda
authors.initials: M
authors.lastname: Adli
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 and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Bermpohl
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Walter
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000503:physiopathology / Q000523:psychology; D005190:Family; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe / Q000503:physiopathology; D010641:Phenotype; D017397:Prefrontal Cortex / Q000503:physiopathology; D000066553:Problem Behavior / Q000523:psychology; D013702:Temporal Lobe / Q000503:physiopathology; D056345:Theory of Mind / Q000502:physiology*
keywords: affective disorders; fMRI; intermediate phenotype; medial prefrontal cortex; mentalizing; neuroimaging; psychosis; temporoparietal junction