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Schizophrenia is a neurodevelopmental disorder whose origins are rooted in complex genetic components. Despite our burgeoning understanding, the pathophysiology of this disorder remains incompletely deciphered.
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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Longitudinal MicroRNA Signature of Conversion to Psychosis.

Anton Iftimovici1,2, Qin He1, Chuan Jiao1

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This summary is machine-generated.

Epigenetic changes involving microRNAs may predict psychosis onset in ultra-high-risk individuals. This study identified specific microRNA variations linked to psychosis development, offering potential biomarkers for early detection and intervention.

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Gene-environment interactions and epigenetic mechanisms, particularly microRNAs, are implicated in psychosis development.
  • The role of microRNAs as predictive biomarkers for psychosis onset in at-risk individuals remains largely unexplored.

Purpose of the Study:

  • To investigate microRNA expression patterns in individuals at ultra-high risk (UHR) for psychosis.
  • To identify specific microRNA variations associated with the conversion to psychosis over time.
  • To explore the potential of microRNAs as pathophysiological biomarkers for psychosis onset.

Main Methods:

  • A longitudinal study involving 81 UHR subjects, with plasma microRNA expression measured at baseline and follow-up using high-throughput sequencing.
  • Combined supervised machine learning and differential graph analysis to identify significant microRNA variations and networks.
  • Univariate models were used to interpret the identified microRNA variations in relation to clinical and demographic factors.

Main Results:

  • Identified 207 microRNA variations significantly contributing to psychosis prediction.
  • Discovered 276 network-specific correlations of microRNA variations.
  • Pinpointed 25 microRNAs with gene targets relevant to cognition and schizophrenia GWAS findings, with miR-150-5p and miR-3191-5p variations showing particular relevance to psychosis onset, independent of covariates.

Conclusions:

  • This study provides the first longitudinal evidence of dynamic epigenetic signatures associated with psychosis conversion.
  • The identified microRNA variations represent potential pathophysiologically relevant biomarkers for predicting psychosis onset.
  • The findings highlight the importance of microRNAs in the transition to psychosis and suggest novel avenues for early intervention.