Manuel Mattheisen

Striatal Response to Reward Anticipation: Evidence for a Systems-Level Intermediate Phenotype for Schizophrenia

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Oliver Grimm, Central Institute of Mental Health Mannheim, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
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  • Andreas Heinz, Department of Psychiatry and Psychotherapy, Charité-University Medicine Berlin, Campus Mitte, Berlin, Germany.
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  • Henrik Walter, Department of Psychiatry and Psychotherapy, Charité-University Medicine Berlin, Campus Mitte, Berlin, Germany.
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  • Peter Kirsch, Central Institute of Mental Health Mannheim, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
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  • Susanne Erk, Department of Psychiatry and Psychotherapy, Charité-University Medicine Berlin, Campus Mitte, Berlin, Germany.
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  • Leila Haddad, Central Institute of Mental Health Mannheim, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
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  • Michael M Plichta, Central Institute of Mental Health Mannheim, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
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  • Nina Romanczuk-Seiferth, Department of Psychiatry and Psychotherapy, Charité-University Medicine Berlin, Campus Mitte, Berlin, Germany.
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  • Lydia Pöhland, Department of Psychiatry and Psychotherapy, Charité-University Medicine Berlin, Campus Mitte, Berlin, Germany.
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  • Sebastian Mohnke, Department of Psychiatry and Psychotherapy, Charité-University Medicine Berlin, Campus Mitte, Berlin, Germany.
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  • Thomas W Mühleisen, Institute of Human Genetics, University of Bonn, Bonn, Germany4Institute of Neuroscience and Medicine, Jülich Research Centre, Jülich, Germany.
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  • Manuel Mattheisen
  • Stephanie H Witt, Central Institute of Mental Health Mannheim, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
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  • Axel Schäfer, Central Institute of Mental Health Mannheim, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
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  • Sven Cichon, Institute of Human Genetics, University of Bonn, Bonn, Germany4Institute of Neuroscience and Medicine, Jülich Research Centre, Jülich, Germany7Department of Genomics, Life and Brain Research Centre, University of Bonn, Bonn, Germany8Department of Biomedic.
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  • Markus Nöthen, Institute of Human Genetics, University of Bonn, Bonn, Germany4Institute of Neuroscience and Medicine, Jülich Research Centre, Jülich, Germany7Department of Genomics, Life and Brain Research Centre, University of Bonn, Bonn, Germany.
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  • Marcella Rietschel, Central Institute of Mental Health Mannheim, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
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  • Heike Tost, Central Institute of Mental Health Mannheim, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
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  • Andreas Meyer-Lindenberg, Central Institute of Mental Health Mannheim, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
IMPORTANCE Attenuated ventral striatal response during reward anticipation is a core feature of schizophrenia that is seen in prodromal, drug-naive, and chronic schizophrenic patients. Schizophrenia is highly heritable, raising the possibility that this phenotype is related to the genetic risk for the disorder. OBJECTIVE To examine a large sample of healthy first-degree relatives of schizophrenic patients and compare their neural responses to reward anticipation with those of carefully matched controls without a family psychiatric history. To further support the utility of this phenotype, we studied its test-retest reliability, its potential brain structural contributions, and the effects of a protective missense variant in neuregulin 1 (NRG1) linked to schizophrenia by meta-analysis (ie, rs10503929). DESIGN, SETTING, AND PARTICIPANTS Examination of a well-established monetary reward anticipation paradigm during functional magnetic resonance imaging at a university hospital; voxel-based morphometry; test-retest reliability analysis of striatal activations in an independent sample of 25 healthy participants scanned twice with the same task; and imaging genetics analysis of the control group. A total of 54 healthy first-degree relatives of schizophrenic patients and 80 controls matched for demographic, psychological, clinical, and task performance characteristics were studied. MAIN OUTCOMES AND MEASURES Blood oxygen level-dependent response during reward anticipation, analysis of intraclass correlations of functional contrasts, and associations between striatal gray matter volume and NRG1 genotype. RESULTS Compared with controls, healthy first-degree relatives showed a highly significant decrease in ventral striatal activation during reward anticipation (familywise error-corrected P .05), and affected by the NRG1 genotype (higher striatal responses in controls with the protective rs10503929 C allele; familywise error-corrected P 
Original languageEnglish
JournalJ A M A Psychiatry
Volume71
Issue5
Pages (from-to)531-539
Number of pages9
ISSN2168-622X
DOIs
Publication statusPublished - 12 Mar 2014

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