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

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abstract

  • 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.

authors

  • 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
  • Soares, Claudio N
  • Müller, Daniel J
  • Farzan, Faranak
  • Leri, Francesco
  • MacQueen, Glenda
  • 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

publication date

  • August 2017