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Record W2617341365 · 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

2017· article· en· W2617341365 on OpenAlexafffund
Juan Pablo López, Laura M. Fiori, Cristiana Cruceanu, Rixing Lin, Benoît Labonté, Hannah M. Cates, Elizabeth A. Heller, Vincent Vialou, Stacy M. Ku, Christophe Gerald, Ming-Hu Han, Jane A. Foster, Benício N. Frey, Claudio N. Soares, Daniel J. Müller, Faranak Farzan, Francesco Leri, Glenda MacQueen, Harriet Feilotter, Kathrin Tyryshkin, Kenneth Evans, Peter Giacobbe, Pierre Blier, Raymond W. Lam, Roumen Milev, Sagar V. Parikh, Susan Rotzinger, Stephen C. Strother, Cathryn M. Lewis, Katherine J. Aitchison, Gayle Wittenberg, Naguib Mechawar, Eric J. Nestler, Rudolf Uher, Sidney H. Kennedy, Gustavo Turecki

Bibliographic record

VenueNature Communications · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMicroRNA in disease regulation
Canadian institutionsUniversity of AlbertaDalhousie UniversityBaycrest HospitalVancouver Coastal HealthUniversity of CalgaryUniversity of GuelphCentre for Addiction and Mental HealthSt. Michael's HospitalQueen's UniversityIndoc ResearchMcMaster UniversityUniversity of British ColumbiaSurrey Memorial HospitalRoyal Ottawa Mental Health CentreSt. Joseph’s Healthcare HamiltonUniversity of TorontoUniversity Health NetworkUniversity of OttawaMcGill UniversityDouglas Mental Health University Institute
FundersFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchGovernment of AlbertaEuropean CommissionNational Institute on Drug AbuseGovernment of OntarioNational Institutes of HealthNational Institute of Mental HealthOntario Brain Institute
KeywordsWnt signaling pathwaymicroRNAMajor depressive disorderAntidepressantDepression (economics)GeneMAPK/ERK pathwayBiologyPlaceboBioinformaticsMedicineInternal medicineOncologyGeneticsSignal transductionHippocampusPathology

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.865
Threshold uncertainty score0.588

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.278
Teacher spread0.265 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations206
Published2017
Admission routes2
Has abstractyes

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