TY  - JOUR
AU  - Solomon, Pierre
AU  - Kaurani, Lalit
AU  - Budde, Monika
AU  - Guiné, Jean-Baptiste
AU  - Krüger, Dennis Manfred
AU  - Riquin, Kevin
AU  - Pena, Tonatiuh
AU  - Burkhardt, Susanne
AU  - Fourgeux, Cynthia
AU  - Adorjan, Kristina
AU  - Heilbronner, Maria
AU  - Kalman, Janos L
AU  - Kohshour, Mojtaba Oraki
AU  - Papiol, Sergi
AU  - Reich-Erkelenz, Daniela
AU  - Schaupp, Sabrina K
AU  - Schulte, Eva C
AU  - Senner, Fanny
AU  - Vogl, Thomas
AU  - Anghelescu, Ion-George
AU  - Arolt, Volker
AU  - Baune, Bernhardt T
AU  - Dannlowski, Udo
AU  - Dietrich, Detlef E
AU  - Fallgatter, Andreas
AU  - Figge, Christian
AU  - Juckel, Georg
AU  - Konrad, Carsten
AU  - Reimer, Jens
AU  - Reininghaus, Eva Z
AU  - Schmauß, Max
AU  - Spitzer, Carsten
AU  - Wiltfang, Jens
AU  - Zimmermann, Jörg
AU  - Schütz, Anna-Lena
AU  - Sananbenesi, Farahnaz
AU  - Sauvaget, Anne
AU  - Falkai, Peter
AU  - Schulze, Thomas G
AU  - Fischer, André
AU  - Heilbronner, Urs
AU  - Poschmann, Jeremie
TI  - Integrative analysis of miRNA expression profiles reveals distinct and common molecular mechanisms underlying broad diagnostic groups of severe mental disorders.
JO  - Molecular psychiatry
VL  - 30
IS  - 9
SN  - 1359-4184
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-00947
SP  - 4364 - 4383
PY  - 2025
AB  - 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.
KW  - Humans
KW  - MicroRNAs: genetics
KW  - MicroRNAs: metabolism
KW  - Bipolar Disorder: genetics
KW  - Male
KW  - Female
KW  - Schizophrenia: genetics
KW  - Schizophrenia: metabolism
KW  - Mental Disorders: genetics
KW  - Gene Expression Profiling: methods
KW  - Adult
KW  - Transcriptome: genetics
KW  - Psychotic Disorders: genetics
KW  - Gene Regulatory Networks: genetics
KW  - Genome-Wide Association Study: methods
KW  - Middle Aged
KW  - MicroRNAs (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40263528
DO  - DOI:10.1038/s41380-025-03018-9
UR  - https://pub.dzne.de/record/280292
ER  -