|Title||MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Auteurs||Lopez, JPablo, Fiori, LM, Cruceanu, C, Lin, R, Labonté, 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|
|Date Published||2017 May 22|
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.