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@ARTICLE{Assmann:154290,
      author       = {Assmann, Anne and Richter, Anni and Schütze, Hartmut and
                      Soch, Joram and Barman, Adriana and Behnisch, Gusalija and
                      Knopf, Lea and Raschick, Matthias and Schult, Annika and
                      Wüstenberg, Torsten and Behr, Joachim and Düzel, Emrah and
                      Seidenbecher, Constanze I and Schott, Björn},
      title        = {{N}eurocan genome-wide psychiatric risk variant affects
                      explicit memory performance and hippocampal function in
                      healthy humans.},
      journal      = {European journal of neuroscience},
      volume       = {53},
      number       = {12},
      issn         = {1460-9568},
      address      = {Oxford [u.a.]},
      publisher    = {Wiley},
      reportid     = {DZNE-2021-00144},
      pages        = {3942-3959},
      year         = {2021},
      note         = {ISSN 1460-9568 not unique: **3 hits**.},
      abstract     = {Alterations of the brain extracellular matrix (ECM) can
                      perturb the structure and function of brain networks like
                      the hippocampus, a key region in human memory that is
                      commonly affected in psychiatric disorders. Here, we
                      investigated the potential effects of a genome-wide
                      psychiatric risk variant in the NCAN gene encoding the ECM
                      proteoglycan neurocan (rs1064395) on memory performance,
                      hippocampal function and cortical morphology in young,
                      healthy volunteers. We assessed verbal memory performance in
                      two cohorts (N = 572, 302) and found reduced recall
                      performance in risk allele (A) carriers across both cohorts.
                      In 117 participants, we performed functional magnetic
                      resonance imaging using a novelty-encoding task with visual
                      scenes. Risk allele carriers showed higher false alarm rates
                      during recognition, accompanied by inefficiently increased
                      left hippocampal activation. To assess effects of rs1064395
                      on brain morphology, we performed voxel-based morphometry in
                      420 participants from four independent cohorts and found
                      lower grey matter density in the ventrolateral and rostral
                      prefrontal cortex of risk allele carriers. In silico eQTL
                      analysis revealed that rs1064395 SNP is linked not only to
                      increased prefrontal expression of the NCAN gene itself, but
                      also of the neighbouring HAPLN4 gene, suggesting a more
                      complex effect of the SNP on ECM composition. Our results
                      suggest that the NCAN rs1064395 A allele is associated with
                      lower hippocampus-dependent memory function, variation of
                      prefrontal cortex structure and ECM composition. Considering
                      the well-documented hippocampal and prefrontal dysfunction
                      in bipolar disorder and schizophrenia, our results may
                      reflect an intermediate phenotype by which NCAN rs1064395
                      contributes to disease risk.},
      keywords     = {Bipolar Disorder / Brain Mapping / Chondroitin Sulfate
                      Proteoglycans: genetics / Hippocampus: diagnostic imaging /
                      Hippocampus: physiology / Humans / Lectins, C-Type: genetics
                      / Magnetic Resonance Imaging / Memory / Nerve Tissue
                      Proteins: genetics / Neurocan: genetics / Schizophrenia /
                      episodic memory (Other) / extracellular matrix (Other) /
                      fMRI (Other) / imaging genetics (Other) / voxel-based
                      morphometry (Other)},
      cin          = {AG Düzel / U Clinical Researchers - Magdeburg},
      ddc          = {610},
      cid          = {I:(DE-2719)5000006 / I:(DE-2719)7000000},
      pnm          = {344 - Clinical and Health Care Research (POF3-344) / 353 -
                      Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF3-344 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32583466},
      doi          = {10.1111/ejn.14872},
      url          = {https://pub.dzne.de/record/154290},
}