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; Gustavo Turecki

doi:10.1038/ncomms15497

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 TyryshkinKenneth 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, Gustavo Turecki

Medicine

Research output: Contribution to journal › Article › peer-review

152 Citations (Scopus)

Abstract

Antidepressants (ADs) are the most common treatment for major depressive disorder (MDD). However, only â 1/430% 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.

Original language	English
Article number	15497
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15497
Publication status	Published - May 22 2017

ASJC Scopus Subject Areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

PubMed: MeSH publication types

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

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10.1038/ncomms15497

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Lopez, J. P., Fiori, L. M., Cruceanu, C., Lin, R., Labonte, B., Cates, H. M., Heller, E. A., Vialou, V., Ku, S. M., Gerald, C., Han, M. H., Foster, J., Frey, B. N., Soares, C. N., Müller, D. J., Farzan, F., Leri, F., Macqueen, G. M., Feilotter, H., ... Turecki, G. (2017). MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes. Nature Communications, 8, Article 15497. https://doi.org/10.1038/ncomms15497

Lopez, JP, Fiori, LM, Cruceanu, C, Lin, R, Labonte, B, Cates, HM, Heller, EA, Vialou, V, Ku, SM, Gerald, C, Han, MH, 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 2017, 'MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes', Nature Communications, vol. 8, 15497. https://doi.org/10.1038/ncomms15497

@article{f58655b8397c400f8253a6e017746afc,

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

abstract = "Antidepressants (ADs) are the most common treatment for major depressive disorder (MDD). However, only {\^a} 1/430% 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.",

author = "Lopez, {Juan Pablo} and Fiori, {Laura M.} and Cristiana Cruceanu and Rixing Lin and Benoit Labonte and Cates, {Hannah M.} and Heller, {Elizabeth A.} and Vincent Vialou and Ku, {Stacy M.} and Christophe Gerald and Han, {Ming Hu} and Jane Foster and Frey, {Benicio N.} and Soares, {Claudio N.} and M{\"u}ller, {Daniel J.} and Faranak Farzan and Francesco Leri and Macqueen, {Glenda M.} and Harriet Feilotter and Kathrin Tyryshkin and Evans, {Kenneth R.} and Peter Giacobbe and Pierre Blier and Lam, {Raymond W.} and Roumen Milev and Parikh, {Sagar V.} and Susan Rotzinger and Strother, {Steven C.} and Lewis, {Cathryn M.} and Aitchison, {Katherine J.} and Wittenberg, {Gayle M.} and Naguib Mechawar and Nestler, {Eric J.} and Rudolf Uher and Kennedy, {Sidney H.} and Gustavo Turecki",

year = "2017",

month = may,

day = "22",

doi = "10.1038/ncomms15497",

language = "English",

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journal = "Nature Communications",

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T1 - MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes

AU - Lopez, Juan Pablo

AU - Fiori, Laura M.

AU - Cruceanu, Cristiana

AU - Lin, Rixing

AU - Labonte, Benoit

AU - Cates, Hannah M.

AU - Heller, Elizabeth A.

AU - Vialou, Vincent

AU - Ku, Stacy M.

AU - Gerald, Christophe

AU - Han, Ming Hu

AU - Foster, Jane

AU - Frey, Benicio N.

AU - Soares, Claudio N.

AU - Müller, Daniel J.

AU - Farzan, Faranak

AU - Leri, Francesco

AU - Macqueen, Glenda M.

AU - Feilotter, Harriet

AU - Tyryshkin, Kathrin

AU - Evans, Kenneth R.

AU - Giacobbe, Peter

AU - Blier, Pierre

AU - Lam, Raymond W.

AU - Milev, Roumen

AU - Parikh, Sagar V.

AU - Rotzinger, Susan

AU - Strother, Steven C.

AU - Lewis, Cathryn M.

AU - Aitchison, Katherine J.

AU - Wittenberg, Gayle M.

AU - Mechawar, Naguib

AU - Nestler, Eric J.

AU - Uher, Rudolf

AU - Kennedy, Sidney H.

AU - Turecki, Gustavo

PY - 2017/5/22

Y1 - 2017/5/22

N2 - Antidepressants (ADs) are the most common treatment for major depressive disorder (MDD). However, only â 1/430% 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.

AB - Antidepressants (ADs) are the most common treatment for major depressive disorder (MDD). However, only â 1/430% 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.

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DO - 10.1038/ncomms15497

M3 - Article

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SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 15497

ER -

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

Abstract

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