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Article Dans Une Revue Schizophrenia Bulletin Année : 2023

Longitudinal MicroRNA Signature of Conversion to Psychosis

Résumé

Abstract Background and Hypothesis The emergence of psychosis in ultra-high-risk subjects (UHR) is influenced by gene-environment interactions that rely on epigenetic mechanisms such as microRNAs. However, whether they can be relevant pathophysiological biomarkers of psychosis’ onset remains unknown. Study Design We present a longitudinal study of microRNA expression, measured in plasma by high-throughput sequencing at baseline and follow-up, in a prospective cohort of 81 UHR, 35 of whom developed psychosis at follow-up (converters). We combined supervised machine learning and differential graph analysis to assess the relative weighted contribution of each microRNA variation to the difference in outcome and identify outcome-specific networks. We then applied univariate models to the resulting microRNA variations common to both strategies, to interpret them as a function of demographic and clinical covariates. Study Results We identified 207 microRNA variations that significantly contributed to the classification. The differential network analysis found 276 network-specific correlations of microRNA variations. The combination of both strategies identified 25 microRNAs, whose gene targets were overrepresented in cognition and schizophrenia genome-wide association studies findings. Interpretable univariate models further supported the relevance of miR-150-5p and miR-3191-5p variations in psychosis onset, independent of age, sex, cannabis use, and medication. Conclusions In this first longitudinal study of microRNA variation during conversion to psychosis, we combined 2 methodologically independent data-driven strategies to identify a dynamic epigenetic signature of the emergence of psychosis that is pathophysiologically relevant.
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inserm-04187662 , version 1 (25-08-2023)

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Anton Iftimovici, Qin He, Chuan Jiao, Edouard Duchesnay, Marie-Odile Krebs, et al.. Longitudinal MicroRNA Signature of Conversion to Psychosis. Schizophrenia Bulletin, 2023, 50 (2), pp.363-373. ⟨10.1093/schbul/sbad080⟩. ⟨inserm-04187662⟩
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