Gast ::
| Hauptseite > Publikationsdatenbank > A miR-137-related biological pathway of risk for Schizophrenia is associated with human brain emotion processing |
| Hauptseite > Publikationsdatenbank > A miR-137-related biological pathway of risk for Schizophrenia is associated with human brain emotion processing |
| Journal Article | FZJ-2023-05147 |
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
2024
Elsevier Inc.
Amsterdam [u.a.]
This record in other databases: 
Please use a persistent id in citations: doi:10.1016/j.bpsc.2023.11.001 doi:10.34734/FZJ-2023-05147
Abstract: 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.
; 
; 
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection
|
The record appears in these collections: |
PDF