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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

Author

Listed:
  • Juan Pablo Lopez

    (McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University)

  • Laura M. Fiori

    (McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University)

  • Cristiana Cruceanu

    (McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University)

  • Rixing Lin

    (McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University)

  • Benoit Labonte

    (Icahn School of Medicine at Mount Sinai)

  • Hannah M. Cates

    (Icahn School of Medicine at Mount Sinai)

  • Elizabeth A. Heller

    (Icahn School of Medicine at Mount Sinai)

  • Vincent Vialou

    (Icahn School of Medicine at Mount Sinai)

  • Stacy M. Ku

    (Icahn School of Medicine at Mount Sinai)

  • Christophe Gerald

    (Icahn School of Medicine at Mount Sinai)

  • Ming-Hu Han

    (Icahn School of Medicine at Mount Sinai)

  • Jane Foster

    (University Health Network, University of Toronto)

  • Benicio N. Frey

    (McMaster University and St Joseph’s Healthcare Hamilton)

  • Claudio N. Soares

    (St Michael’s Hospital
    Queen’s University)

  • Daniel J. Müller

    (University Health Network, University of Toronto
    Centre for Addiction and Mental Health)

  • Faranak Farzan

    (University Health Network, University of Toronto
    Centre for Addiction and Mental Health
    School of Mechatronic Systems Engineering)

  • Francesco Leri

    (University of Guelph)

  • Glenda M. MacQueen

    (University of Calgary Hotchkiss Brain Institute)

  • Harriet Feilotter

    (Queen’s University)

  • Kathrin Tyryshkin

    (Queen’s University)

  • Kenneth R. Evans

    (Queen’s University
    Indoc Research)

  • Peter Giacobbe

    (University Health Network, University of Toronto)

  • Pierre Blier

    (University of Ottawa Institute of Mental Health Research)

  • Raymond W. Lam

    (University of British Columbia and Vancouver Coastal Health Authority)

  • Roumen Milev

    (Queen’s University, Providence Care, Mental Health Services)

  • Sagar V. Parikh

    (University of Michigan)

  • Susan Rotzinger

    (University Health Network, University of Toronto)

  • Steven C. Strother

    (Rotman Research Institute at Baycrest Centre)

  • Cathryn M. Lewis

    (MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London)

  • Katherine J. Aitchison

    (University of Alberta
    Dalhousie University)

  • Gayle M. Wittenberg

    (Janssen Research & Development, LLC)

  • Naguib Mechawar

    (McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University)

  • Eric J. Nestler

    (Icahn School of Medicine at Mount Sinai)

  • Rudolf Uher

    (MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
    Dalhousie University)

  • Sidney H. Kennedy

    (University Health Network, University of Toronto)

  • Gustavo Turecki

    (McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University)

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.

Suggested Citation

  • 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 Fos, 2017. "MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15497
    DOI: 10.1038/ncomms15497
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