MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes

Juan Pablo Lopez, Laura M. Fiori, Cristiana Cruceanu, Rixing Lin, Benoit Labonte, Hannah M. Cates, Elizabeth A. Heller, Vincent Vialou, Stacy M. Ku, Christophe Gerald, Ming Hu Han, Jane Foster, Benicio N. Frey, Claudio N. Soares, Daniel J. Müller, Faranak Farzan, Francesco Leri, Glenda M. Macqueen, Harriet Feilotter, Kathrin TyryshkinKenneth R. Evans, Peter Giacobbe, Pierre Blier, Raymond W. Lam, Roumen Milev, Sagar V. Parikh, Susan Rotzinger, Steven C. Strother, Cathryn M. Lewis, Katherine J. Aitchison, Gayle M. Wittenberg, Naguib Mechawar, Eric J. Nestler, Rudolf Uher, Sidney H. Kennedy, Gustavo Turecki

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Antidepressants (ADs) are the most common treatment for major depressive disorder (MDD). However, only â 1/430% 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.

Original languageEnglish (US)
Article number15497
JournalNature communications
Volume8
DOIs
StatePublished - May 22 2017
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • General
  • Physics and Astronomy(all)

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