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<p>Micro RNAs (miRNAs) play a crucial role as regulators of various biological processes and have been implicated in the pathogenesis of mental disorders such as schizophrenia and bipolar disorders. In this study, we investigate the expression patterns of miRNAs in the PsyCourse Study (<i>n</i> = 1786), contrasting three broad diagnostic groups: Psychotic (Schizophrenia-spectrum disorders), Affective (Bipolar Disorder I, II and recurrent Depression), and neurotypic healthy individuals. Through comprehensive analyses, including differential miRNA expression, miRNA transcriptome-wide association study (TWAS), and predictive modelling, we identified multiple miRNAs unique to Psychotic and Affective groups as well as shared by both. Furthermore, we performed integrative analysis to identify the target genes of the dysregulated miRNAs and elucidate their potential roles in psychosis. Our findings reveal significant alterations of multiple miRNAs such as miR-584-3p and miR-99b-5p across the studied diagnostic groups, highlighting their role as molecular correlates. Additionally, the miRNA TWAS analysis discovered previously known and novel genetically dysregulated miRNAs confirming the relevance in the etiology of the diagnostic groups. Importantly, novel factors and putative molecular mechanisms underlying these groups were uncovered through the integration of miRNA-target gene interactions. This comprehensive investigation provides valuable insights into the molecular underpinnings of severe mental disorders, shedding light on the complex regulatory networks involving miRNAs.</p>

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Integrative analysis of miRNA expression profiles reveals distinct and common molecular mechanisms underlying broad diagnostic groups of severe mental disorders

  • 期刊论文

  • 发表日期：

    2025年4月23日

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  • Pierre Solomon,
  • Lalit Kaurani,
  • Monika Budde,
  • Jean-Baptiste Guiné,
  • Dennis Manfred Krüger,
  • Kevin Riquin,
  • Tonatiuh Pena,
  • Susanne Burkhardt,
  • Cynthia Fourgeux,
  • Kristina Adorjan,
  • Maria Heilbronner,
  • Janos L. Kalman,
  • Mojtaba Oraki Kohshour,
  • Sergi Papiol,
  • Daniela Reich-Erkelenz,
  • Sabrina K. Schaupp,
  • Eva C. Schulte,
  • Fanny Senner,
  • Thomas Vogl,
  • Ion-George Anghelescu,
  • Volker Arolt,
  • Bernhardt T. Baune,
  • Udo Dannlowski,
  • Detlef E. Dietrich,
  • Andreas J. Fallgatter,
  • Christian Figge,
  • Georg Juckel,
  • Carsten Konrad,
  • Jens Reimer,
  • Eva Z. Reininghaus,
  • Max Schmauß,
  • Carsten Spitzer,
  • Jens Wiltfang,
  • Jörg Zimmermann,
  • Anna-Lena Schütz,
  • Farahnaz Sananbenesi,
  • Anne Sauvaget,
  • Peter Falkai,
  • Thomas G. Schulze,
  • André Fischer,
  • Urs Heilbronner,
  • Jeremie Poschmann

摘要

Micro RNAs (miRNAs) play a crucial role as regulators of various biological processes and have been implicated in the pathogenesis of mental disorders such as schizophrenia and bipolar disorders. In this study, we investigate the expression patterns of miRNAs in the PsyCourse Study (n = 1786), contrasting three broad diagnostic groups: Psychotic (Schizophrenia-spectrum disorders), Affective (Bipolar Disorder I, II and recurrent Depression), and neurotypic healthy individuals. Through comprehensive analyses, including differential miRNA expression, miRNA transcriptome-wide association study (TWAS), and predictive modelling, we identified multiple miRNAs unique to Psychotic and Affective groups as well as shared by both. Furthermore, we performed integrative analysis to identify the target genes of the dysregulated miRNAs and elucidate their potential roles in psychosis. Our findings reveal significant alterations of multiple miRNAs such as miR-584-3p and miR-99b-5p across the studied diagnostic groups, highlighting their role as molecular correlates. Additionally, the miRNA TWAS analysis discovered previously known and novel genetically dysregulated miRNAs confirming the relevance in the etiology of the diagnostic groups. Importantly, novel factors and putative molecular mechanisms underlying these groups were uncovered through the integration of miRNA-target gene interactions. This comprehensive investigation provides valuable insights into the molecular underpinnings of severe mental disorders, shedding light on the complex regulatory networks involving miRNAs.