A miR-137–Related Biological Pathway of Risk for Schizophrenia Is Associated With Human Brain Emotion Processing

• DOI: 10.1016/j.bpsc.2023.11.001
• Publication Date: 2023-11-22T19:21:14Z
• Authors: Giulio Pergola; Antonio Rampino; Leonardo Sportelli; Christopher James...; Roberta Passiatore; Pasquale Di Carlo; Aleksandra Marakh...; Leonardo Fazio; Nicola Amoroso; Mariana Nair Castro; Enrico Domenici; Massimo Gennarelli; Jivan Khlghatyan; Gianluca Christos...; 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
• Keywords: Human brain; Genome-wide Association Study; Dorsolateral prefrontal cortex

MiR-137 is a microRNA involved in brain development, regulating neurogenesis and neuronal maturation. Genome-Wide Association Studies implicate miR-137 schizophrenia risk but do not explain its involvement function underlying biology. Polygenic for mediated by targets associated with working memory, although other evidence points to emotion processing. We characterized the functional correlates of target genes while disentangling previously reported associations memory Using RNA-sequencing data from postmortem prefrontal cortex (N=522), we identified co-expression gene set enriched genes. validated relationship this in-vitro manipulating expression neuroblastoma cells. translated into polygenic scores prediction them fMRI activation healthy volunteers (N1=214; N2=136; N3=2,075; N4=1,800) short-term treatment response patients (N=427). In 4,652 human subjects, found that (i) are co-expressed biologically targets, (ii) increased low expression, (iii) alleles predicting greater gene-set during processing three independent cohorts (N1-2-3), interaction age (N4), (iv) these predict less improvement negative symptoms following antipsychotic schizophrenia. The translation linked involves