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

TitleMicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes.
Publication TypeJournal Article
Year of Publication2017
AuthorsLopez JPablo, Fiori LM, Cruceanu C, Lin R, Labonte B, Cates HM, Heller EA, Vialou V, Ku SM, Gerald C, Han M-H, Foster J, Frey BN, Soares CN, Müller DJ, Farzan F, Leri F, Macqueen GM, Feilotter H, Tyryshkin K, Evans KR, Giacobbe P, Blier P, Lam RW, Milev R, Parikh SV, Rotzinger S, Strother SC, Lewis CM, Aitchison KJ, Wittenberg GM, Mechawar N, Nestler EJ, Uher R, Kennedy SH, Turecki G
JournalNat Commun
Volume8
Pagination15497
Date Published2017 May 22
ISSN2041-1723
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.

DOI10.1038/ncomms15497
Alternate JournalNat Commun
PubMed ID28530238
PubMed Central IDPMC5477510
Grant ListR01 DA033684 / DA / NIDA NIH HHS / United States

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