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

Nat Commun. 2017 May 22;8:15497. doi: 10.1038/ncomms15497.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antidepressive Agents / therapeutic use
  • Biomarkers
  • Brain / pathology
  • Computational Biology
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / genetics
  • Duloxetine Hydrochloride / therapeutic use*
  • Female
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • Middle Aged
  • Wnt Signaling Pathway
  • Young Adult

Substances

  • Antidepressive Agents
  • Biomarkers
  • MIRN146 microRNA, human
  • MIRN24 microRNA, human
  • MIRN425 microRNA, human
  • MIRN425 microRNA, mouse
  • MicroRNAs
  • Mirn146 microRNA, mouse
  • Mirn24 microRNA, mouse
  • Duloxetine Hydrochloride