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 Tyryshkin, Kenneth 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 and Gustavo Turecki ()
Additional contact information
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
Daniel J. Müller: University Health Network, University of Toronto
Faranak Farzan: University Health Network, University of Toronto
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
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
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
Sidney H. Kennedy: University Health Network, University of Toronto
Gustavo Turecki: McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15497

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