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@ARTICLE{Pergola:1019094,
      author       = {Pergola, Giulio and Rampino, Antonio and Sportelli,
                      Leonardo and Borcuk, Christopher James and Passiatore,
                      Roberta and Di Carlo, Pasquale and Marakhovskaia, Aleksandra
                      and Fazio, Leonardo and Amoroso, Nicola and Castro, Mariana
                      Nair and Domenici, Enrico and Gennarelli, Massimo and
                      Khlghatyan, Jivan and Kikidis, Gianluca Christos and Lella,
                      Annalisa and Magri, Chiara and Monaco, Alfonso and Papalino,
                      Marco and Parihar, Madhur and Popolizio, Teresa and Quarto,
                      Tiziana and Romano, Raffaella and Torretta, Silvia and
                      Valsecchi, Paolo and Zunuer, Hediche and Blasi, Giuseppe and
                      Dukart, Jürgen and Beaulieu, Jean Martin and Bertolino,
                      Alessandro},
      title        = {{A} mi{R}-137-related biological pathway of risk for
                      {S}chizophrenia is associated with human brain emotion
                      processing},
      journal      = {Biological psychiatry / Cognitive neuroscience and
                      neuroimaging},
      volume       = {9},
      number       = {3},
      issn         = {2451-9022},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Inc.},
      reportid     = {FZJ-2023-05147},
      pages        = {356-366},
      year         = {2024},
      abstract     = {BackgroundMiR-137 is a microRNA involved in brain
                      development, regulating neurogenesis and neuronal
                      maturation. Genome-Wide Association Studies implicate
                      miR-137 in schizophrenia risk but do not explain its
                      involvement in brain function and underlying biology.
                      Polygenic risk for schizophrenia mediated by miR-137 targets
                      is associated with working memory, although other evidence
                      points to emotion processing. We characterized the
                      functional brain correlates of miR-137 target genes
                      associated with schizophrenia while disentangling previously
                      reported associations of miR-137 targets with working memory
                      and emotion processing.MethodsUsing RNA-sequencing data from
                      postmortem prefrontal cortex (N=522), we identified a
                      co-expression gene set enriched for miR-137 targets and
                      schizophrenia risk genes. We validated the relationship of
                      this set to miR-137 in-vitro by manipulating miR-137
                      expression in neuroblastoma cells. We translated this gene
                      set into polygenic scores of co-expression prediction and
                      associated them with fMRI activation in healthy volunteers
                      (N1=214; N2=136; N3=2,075; N4=1,800) and with short-term
                      treatment response in patients with schizophrenia
                      (N=427).ResultsIn 4,652 human subjects, we found that (i)
                      schizophrenia risk genes are co-expressed in a biologically
                      validated set enriched for miR-137 targets, (ii) increased
                      expression of miR-137 target risk genes is mediated by low
                      prefrontal miR-137 expression, (iii) alleles predicting
                      greater gene-set co-expression are associated with greater
                      prefrontal activation during emotion processing in three
                      independent healthy cohorts (N1-2-3), in interaction with
                      age (N4), (iv) these alleles predict less improvement in
                      negative symptoms following antipsychotic treatment in
                      patients with schizophrenia.},
      cin          = {INM-7},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {5252 - Brain Dysfunction and Plasticity (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5252},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {38000716},
      UT           = {WOS:001207230300001},
      doi          = {10.1016/j.bpsc.2023.11.001},
      url          = {https://juser.fz-juelich.de/record/1019094},
}