%0 Journal Article
%A Pergola, Giulio
%A Rampino, Antonio
%A Sportelli, Leonardo
%A Borcuk, Christopher James
%A Passiatore, Roberta
%A Di Carlo, Pasquale
%A Marakhovskaia, Aleksandra
%A Fazio, Leonardo
%A Amoroso, Nicola
%A Castro, Mariana Nair
%A Domenici, Enrico
%A Gennarelli, Massimo
%A Khlghatyan, Jivan
%A Kikidis, Gianluca Christos
%A Lella, Annalisa
%A Magri, Chiara
%A Monaco, Alfonso
%A Papalino, Marco
%A Parihar, Madhur
%A Popolizio, Teresa
%A Quarto, Tiziana
%A Romano, Raffaella
%A Torretta, Silvia
%A Valsecchi, Paolo
%A Zunuer, Hediche
%A Blasi, Giuseppe
%A Dukart, Jürgen
%A Beaulieu, Jean Martin
%A Bertolino, Alessandro
%T A miR-137-related biological pathway of risk for Schizophrenia is associated with human brain emotion processing
%J Biological psychiatry / Cognitive neuroscience and neuroimaging
%V 9
%N 3
%@ 2451-9022
%C Amsterdam [u.a.]
%I Elsevier Inc.
%M FZJ-2023-05147
%P 356-366
%D 2024
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 38000716
%U <Go to ISI:>//WOS:001207230300001
%R 10.1016/j.bpsc.2023.11.001
%U https://juser.fz-juelich.de/record/1019094