Theory of mind network activity is altered in subjects with familial liability for schizophrenia.
As evidenced by a multitude of studies, abnormalities in Theory of Mind (ToM) and its neural processing might constitute an intermediate phenotype of schizophrenia. If so, neural alterations during ToM should be observable in unaffected relatives of patients as well, since they share a considerable amount of genetic risk. While behaviorally, impaired ToM function is confirmed meta-analytically in relatives, evidence on aberrant function of the neural ToM network is sparse and inconclusive. The present study therefore aimed to further explore the neural correlates of ToM in relatives of schizophrenia. About 297 controls and 63 unaffected first-degree relatives of patients with schizophrenia performed a ToM task during functional magnetic resonance imaging. Consistent with the literature relatives exhibited decreased activity of the medial prefrontal cortex. Additionally, increased recruitment of the right middle temporal gyrus and posterior cingulate cortex was found, which was related to subclinical paranoid symptoms in relatives. These results further support decreased medial prefrontal activation during ToM as an intermediate phenotype of genetic risk for schizophrenia. Enhanced recruitment of posterior ToM areas in relatives might indicate inefficiency mechanisms in the presence of genetic risk.
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany, sebastian.mohnke@charite.de.
Sebastian
S
Mohnke
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Susanne
S
Erk
Department of Psychiatry, University of Heidelberg, Heidelberg, Germany.
Knut
K
Schnell
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Nina
N
Romanczuk-Seiferth
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Phöbe
P
Schmierer
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Lydia
L
Romund
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Maria
M
Garbusow
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Carolin
C
Wackerhagen
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany, Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Stephan
S
Ripke
Department of Psychiatry, Central Institute of Mental Health, Mannheim/University of Heidelberg; Germany, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zürich, Zürich, Switzerland.
Oliver
O
Grimm
Department of Psychiatry, Central Institute of Mental Health, Mannheim/University of Heidelberg; Germany.
Leila
L
Haller
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim/University of Heidelberg, Germany, and.
Stephanie H
SH
Witt
Department of Genomics, Institute of Human Genetics, Life and Brain Center, University of Bonn, Bonn, Germany.
Franziska
F
Degenhardt
Department of Psychiatry, Central Institute of Mental Health, Mannheim/University of Heidelberg; Germany.
Heike
H
Tost
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Andreas
A
Heinz
Department of Psychiatry, Central Institute of Mental Health, Mannheim/University of Heidelberg; Germany.
Andreas
A
Meyer-Lindenberg
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Henrik
H
Walter
D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013702:Temporal Lobe / Q000503:physiopathology*; D056345:Theory of Mind / Q000502:physiology*; D055815:Young Adult
imaging genetics; intermediate phenotype; medial prefrontal cortex; mentalizing; psychosis