TY  - JOUR
AU  - Pergola, Giulio
AU  - Rampino, Antonio
AU  - Sportelli, Leonardo
AU  - Borcuk, Christopher James
AU  - Passiatore, Roberta
AU  - Di Carlo, Pasquale
AU  - Marakhovskaia, Aleksandra
AU  - Fazio, Leonardo
AU  - Amoroso, Nicola
AU  - Castro, Mariana Nair
AU  - Domenici, Enrico
AU  - Gennarelli, Massimo
AU  - Khlghatyan, Jivan
AU  - Kikidis, Gianluca Christos
AU  - Lella, Annalisa
AU  - Magri, Chiara
AU  - Monaco, Alfonso
AU  - Papalino, Marco
AU  - Parihar, Madhur
AU  - Popolizio, Teresa
AU  - Quarto, Tiziana
AU  - Romano, Raffaella
AU  - Torretta, Silvia
AU  - Valsecchi, Paolo
AU  - Zunuer, Hediche
AU  - Blasi, Giuseppe
AU  - Dukart, Jürgen
AU  - Beaulieu, Jean Martin
AU  - Bertolino, Alessandro
TI  - A miR-137-related biological pathway of risk for Schizophrenia is associated with human brain emotion processing
JO  - Biological psychiatry / Cognitive neuroscience and neuroimaging
VL  - 9
IS  - 3
SN  - 2451-9022
CY  - Amsterdam [u.a.]
PB  - Elsevier Inc.
M1  - FZJ-2023-05147
SP  - 356-366
PY  - 2024
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 38000716
UR  - <Go to ISI:>//WOS:001207230300001
DO  - DOI:10.1016/j.bpsc.2023.11.001
UR  - https://juser.fz-juelich.de/record/1019094
ER  -