Manuel Mattheisen

Identification of gene ontologies linked to prefrontal-hippocampal functional coupling in the human brain

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

  • Luanna Dixson, Departments of Psychiatry and Psychotherapy and., Denmark
  • Henrik Walter, Department of Psychiatry, Division of Mind and Brain Research, Charité Campus Mitte, 10117 Berlin, Germany;
  • ,
  • Michael Schneider, Departments of Psychiatry and Psychotherapy and., Denmark
  • Susanne Erk, Department of Psychiatry, Division of Mind and Brain Research, Charité Campus Mitte, 10117 Berlin, Germany;
  • ,
  • Axel Schäfer, Departments of Psychiatry and Psychotherapy and.
  • ,
  • Leila Haddad, Departments of Psychiatry and Psychotherapy and.
  • ,
  • Oliver Grimm, Departments of Psychiatry and Psychotherapy and.
  • ,
  • Manuel Mattheisen
  • Markus M Nöthen, Department of Genomics, Life and Brain Center,Institute of Human Genetics, andInstitute of Human Genetics, and.
  • ,
  • Sven Cichon, Department of Genomics, Life and Brain Center,Institute of Human Genetics, and.
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  • Stephanie H Witt, Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
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  • Marcella Rietschel, Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
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  • Sebastian Mohnke, Department of Psychiatry, Division of Mind and Brain Research, Charité Campus Mitte, 10117 Berlin, Germany;
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  • Nina Seiferth, Department of Psychiatry, Division of Mind and Brain Research, Charité Campus Mitte, 10117 Berlin, Germany;
  • ,
  • Andreas Heinz, Department of Psychiatry, Division of Mind and Brain Research, Charité Campus Mitte, 10117 Berlin, Germany;
  • ,
  • Heike Tost, Departments of Psychiatry and Psychotherapy and.
  • ,
  • Andreas Meyer-Lindenberg, Departments of Psychiatry and Psychotherapy and a.meyer-lindenberg@zi-mannheim.de.

Functional interactions between the dorsolateral prefrontal cortex and hippocampus during working memory have been studied extensively as an intermediate phenotype for schizophrenia. Coupling abnormalities have been found in patients, their unaffected siblings, and carriers of common genetic variants associated with schizophrenia, but the global genetic architecture of this imaging phenotype is unclear. To achieve genome-wide hypothesis-free identification of genes and pathways associated with prefrontal-hippocampal interactions, we combined gene set enrichment analysis with whole-genome genotyping and functional magnetic resonance imaging data from 269 healthy German volunteers. We found significant enrichment of the synapse organization and biogenesis gene set. This gene set included known schizophrenia risk genes, such as neural cell adhesion molecule (NRCAM) and calcium channel, voltage-dependent, beta 2 subunit (CACNB2), as well as genes with well-defined roles in neurodevelopmental and plasticity processes that are dysfunctional in schizophrenia and have mechanistic links to prefrontal-hippocampal functional interactions. Our results demonstrate a readily generalizable approach that can be used to identify the neurogenetic basis of systems-level phenotypes. Moreover, our findings identify gene sets in which genetic variation may contribute to disease risk through altered prefrontal-hippocampal functional interactions and suggest a link to both ongoing and developmental synaptic plasticity.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
ISSN0027-8424
DOIs
Publication statusPublished - 16 Jun 2014
Externally publishedYes

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