A miR-137-related biological pathway of risk for Schizophrenia is associated with human brain emotion processing

Giulio Pergola; Antonio Rampino; Leonardo Sportelli; Christopher Borcuk; Roberta Passiatore; Pasquale Di Carlo; Aleksandra Marakhovskaia; Leonardo Fazio; Nicola Amoroso; Mariana Nair Castro; Enrico Domenici; Massimo Gennarelli; Jivan Khlghatyan; Gianluca Christos Kikidis; Annalisa Lella; Chiara Magri; Alfonso Monaco; Marco Papalino; Madhur Parihar; Teresa Popolizio; Tiziana Quarto; Raffaella Romano; Silvia Torretta; Paolo Valsecchi; Hailiqiguli Zunuer; Giuseppe Blasi; Juergen Dukart; Jean‐Martin Beaulieu; Alessandro Bertolino

doi:10.1016/j.bpsc.2023.11.001

NeuroscienceBiological Psychiatry Cognitive Neuroscience and NeuroimagingNov 22, 2023

Peer-reviewed journal article

A miR-137-related biological pathway of risk for Schizophrenia is associated with human brain emotion processing

Giulio Pergola iD, Antonio Rampino iD, Leonardo Sportelli iD, Christopher Borcuk iD, Roberta Passiatore iD, Pasquale Di Carlo iD, Aleksandra Marakhovskaia, Leonardo Fazio iD, Nicola Amoroso iD, Mariana Nair Castro iD, Enrico Domenici iD, Massimo Gennarelli iD, Jivan Khlghatyan, Gianluca Christos Kikidis iD, Annalisa Lella iD, Chiara Magri iD, Alfonso Monaco iD, Marco Papalino, Madhur Parihar iD, Teresa Popolizio iD, Tiziana Quarto, Raffaella Romano, Silvia Torretta iD, Paolo Valsecchi iD, Hailiqiguli Zunuer, , Alessandro Bertolino iD

Abstract

Genome-Wide-Association studies have involved miR-137 in schizophrenia. However, the biology underlying this statistical evidence is unclear. Statistical polygenic risk for schizophrenia is associated with working memory, while other biological evidence involves miR-137 in emotion processing. We investigated the function of miR-137 target schizophrenia risk genes in humans. We identified a prefrontal co-expression pathway of schizophrenia-associated miR-137 targets and validated the association with miR-137 expression in neuroblastoma cells. Alleles predicting greater co-expression of this pathway were associated with greater prefrontal activation during emotion processing in two independent cohorts of healthy volunteers (N1=222; N2=136). Statistical polygenic risk for schizophrenia was instead associated with prefrontal activation during working memory. A co-expression pathway links miR-137 and its target genes to emotion processing and risk for schizophrenia. Low prefrontal miR-137 expression may be related with SCZ risk via increased expression of target risk genes, itself associated with increased prefrontal activation during emotion processing.

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