MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes
Nature Publishing Group, 2017
academicJournal
Zugriff:
Antidepressants (ADs) are the most common treatment for major depressive disorder (MDD). However, only ∼30% of patients experience adequate response after a single AD trial, and this variability remains poorly understood. Here, we investigated microRNAs (miRNAs) as biomarkers of AD response using small RNA-sequencing in paired samples from MDD patients enrolled in a large, randomized placebo-controlled trial of duloxetine collected before and 8 weeks after treatment. Our results revealed differential expression of miR-146a-5p, miR-146b-5p, miR-425-3p and miR-24-3p according to treatment response. These results were replicated in two independent clinical trials of MDD, a well-characterized animal model of depression, and post-mortem human brains. Furthermore, using a combination of bioinformatics, mRNA studies and functional in vitro experiments, we showed significant dysregulation of genes involved in MAPK/Wnt signalling pathways. Together, our results indicate that these miRNAs are consistent markers of treatment response and regulators of the MAPK/Wnt systems.
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MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes
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Autor/in / Beteiligte Person: | Lopez, Juan Pablo ; Fiori, Laura M. ; Cruceanu, Cristiana ; Lin, Rixing ; Labonte, Benoit ; Cates, Hannah M. ; Heller, Elizabeth A. ; Vialou, Vincent ; Ku, Stacy M. ; Gerald, Christophe ; Han, Ming-Hu ; Foster, Jane ; Frey, Benicio N. ; Soares, Claudio N. ; Müller, Daniel J. ; Farzan, Faranak ; Leri, Francesco ; MacQueen, Glenda M. ; Feilotter, Harriet ; Tyryshkin, Kathrin ; Evans, Kenneth R. ; Giacobbe, Peter ; Blier, Pierre ; Lam, Raymond W. ; Milev, Roumen ; Parikh, Sagar V. ; Rotzinger, Susan ; Strother, Steven C. ; Lewis, Cathryn M. ; Aitchison, Katherine J. ; Wittenberg, Gayle M. ; Mechawar, Naguib ; Nestler, Eric J. ; Uher, Rudolf ; Kennedy, Sidney H. ; Turecki, Gustavo |
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Veröffentlichung: | Nature Publishing Group, 2017 |
Medientyp: | academicJournal |
DOI: | 10.1038/ncomms15497 |
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