| Title: | A miR-137-Related Biological Pathway of Risk for Schizophrenia Is Associated With Human Brain Emotion Processing |
| Journal: | Biological Psychiatry Cognitive Neuroscience and Neuroimaging |
| Published: | 22 Nov 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38000716/ |
| DOI: | https://doi.org/10.1016/j.bpsc.2023.11.001 |
| Citations: | 2 (2 in last 2 years) as of 8 Aug 2024 |
Publication 12196
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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.</p>
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).</p>
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.</p>
CONCLUSIONS: The functional translation of miR-137 target gene expression linked with schizophrenia involves the neural substrates of emotion processing.</p>
29 Authors
- Giulio Pergola
- Antonio Rampino
- Leonardo Sportelli
- Christopher James 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
1 Application
| Application ID | Title |
|---|---|
| 41655 | Characterizing brain networks and their inter-individual variability by high-throughput imaging and computational modelling |
Enabling scientific discoveries that improve human health