MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes.
Juan Pablo LopezLaura M FioriCristiana CruceanuRixing LinBenoit LabonteHannah M CatesElizabeth A HellerVincent VialouStacy M KuChristophe GeraldMing-Hu HanJane FosterBenicio N FreyClaudio N SoaresDaniel J MüllerFaranak FarzanFrancesco LeriGlenda M MacQueenHarriet FeilotterKathrin TyryshkinKenneth R EvansPeter GiacobbePierre BlierRaymond W LamRoumen V MilevSagar V ParikhSusan RotzingerSteven C StrotherCathryn M LewisKatherine J AitchisonGayle M WittenbergNaguib MechawarEric J NestlerRudolf UherSidney H KennedyGustavo TureckiPublished in: Nature communications (2017)
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.
Keyphrases
- major depressive disorder
- bipolar disorder
- end stage renal disease
- clinical trial
- stem cells
- ejection fraction
- signaling pathway
- chronic kidney disease
- newly diagnosed
- cell proliferation
- double blind
- peritoneal dialysis
- prognostic factors
- randomized controlled trial
- open label
- gene expression
- mass spectrometry
- combination therapy
- single molecule