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

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dc.contributor.author Pergola, Giulio
dc.contributor.author Rampino, Antonio
dc.contributor.author Sportelli, Leonardo
dc.contributor.author Borcuk, Christopher James
dc.contributor.author Passiatore, Roberta
dc.contributor.author Di Carlo, Pasquale
dc.contributor.author Marakhovskaia, Aleksandra
dc.contributor.author Fazio, Leonardo
dc.contributor.author Amoroso, Nicola
dc.contributor.author Castro, Mariana Nair
dc.contributor.author Domenici, Enrico
dc.contributor.author Gennarelli, Massimo
dc.contributor.author Khlghatyan, Jivan
dc.contributor.author Christos Kikidis, Gianluca
dc.contributor.author Lella, Annalisa
dc.contributor.author Magri, Chiara
dc.contributor.author Monaco, Alfonso
dc.contributor.author Papalino, Marco
dc.contributor.author Parihar, Madhur
dc.contributor.author Popolizio, Teresa
dc.date.accessioned 2024-03-28T14:54:51Z
dc.date.available 2024-03-28T14:54:51Z
dc.date.issued 2023-11-22
dc.identifier.citation Pergola G, Rampino A, Sportelli L, Borcuk CJ, Passiatore R, Di Carlo P, et al. A miR-137-related biological pathway of risk for Schizophrenia is associated with human brain emotion processing. Biol Psychiatry Cogn Neurosci Neuroimaging. 22 de noviembre de 2023;S2451-9022(23)00311-7. es_ES
dc.identifier.uri https://doi.org/10.1016/j.bpsc.2023.11.001
dc.identifier.uri https://repositorio.fleni.org.ar/xmlui/handle/123456789/1053
dc.description.abstract Background: miR-137 is a microRNA involved in brain development, regulating neurogenesis and neuronal maturation. Genome-wide association studies have implicated 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. Methods: Using RNA sequencing data from postmortem prefrontal cortex (N = 522), we identified a coexpression 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 coexpression prediction and associated them with functional magnetic resonance imaging activation in healthy volunteers (n1 = 214; n2 = 136; n3 = 2075; n4 = 1800) and with short-term treatment response in patients with schizophrenia (N = 427). Results: In 4652 human participants, we found that 1) schizophrenia risk genes were coexpressed in a biologically validated set enriched for miR-137 targets; 2) increased expression of miR-137 target risk genes was mediated by low prefrontal miR-137 expression; 3) alleles that predict greater gene set coexpression were associated with greater prefrontal activation during emotion processing in 3 independent healthy cohorts (n1, n2, n3) in interaction with age (n4); and 4) these alleles predicted less improvement in negative symptoms following antipsychotic treatment in patients with schizophrenia. Conclusions: The functional translation of miR-137 target gene expression linked with schizophrenia involves the neural substrates of emotion processing. es_ES
dc.language.iso eng es_ES
dc.publisher Elsevier es_ES
dc.subject Emotions es_ES
dc.subject Emociones es_ES
dc.subject Genome-Wide Association Study es_ES
dc.subject Estudio de Asociación del Genoma Completo es_ES
dc.subject MicroRNAs es_ES
dc.subject MicroARNs es_ES
dc.subject Schizophrenia es_ES
dc.subject Esquizofrenia es_ES
dc.title A miR-137-Related Biological Pathway of Risk for Schizophrenia Is Associated With Human Brain Emotion Processing es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.description.fil Fil: Castro, Mariana Nair. Fleni. Instituto de Neurociencias FLENI-CONICET. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.relation.ispartofVOLUME 9
dc.relation.ispartofNUMBER 3
dc.relation.ispartofPAGINATION 356-366
dc.relation.ispartofCOUNTRY Estados Unidos
dc.relation.ispartofCITY Nueva York
dc.relation.ispartofTITLE Biological psychiatry. Cognitive neuroscience and neuroimaging
dc.relation.ispartofISSN 2451-9030
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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