MicroRNAs as biomarkers for major depression: A role for let-7b and let-7c

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dc.contributor.authorGururajan, Anand
dc.contributor.authorNaughton, Maura
dc.contributor.authorScott, Karen A.
dc.contributor.authorO'Connor, R. M.
dc.contributor.authorMoloney, Gerard M.
dc.contributor.authorClarke, Gerard
dc.contributor.authorDowling, J.
dc.contributor.authorWalsh, A.
dc.contributor.authorIsmail, F.
dc.contributor.authorShorten, George
dc.contributor.authorScott, Lucinda V.
dc.contributor.authorMcLoughlin, D. M.
dc.contributor.authorCryan, John F.
dc.contributor.authorDinan, Timothy G.
dc.contributor.funderHealth Research Boarden
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderSeventh Framework Programmeen
dc.contributor.funderBrain and Behavior Research Foundationen
dc.date.accessioned2019-10-30T06:13:18Z
dc.date.available2019-10-30T06:13:18Z
dc.date.issued2016-08-02
dc.description.abstractThere is a growing emphasis in the field of psychiatry on the need to identify candidate biomarkers to aid in diagnosis and clinical management of depression, particularly with respect to predicting response to specific therapeutic strategies. MicroRNAs are small nucleotide sequences with the ability to regulate gene expression at the transcriptomic level and emerging evidence from a range of studies has highlighted their biomarker potential. Here we compared healthy controls (n=20) with patients diagnosed with major depression (n=40) and who were treatment-resistant to identify peripheral microRNA biomarkers, which could be used for diagnosis and to predict response to electroconvulsive therapy (ECT) and ketamine (KET) infusions, treatments that have previously shown to be effective in treatment-resistant depression (TRD). At baseline and after treatment, blood samples were taken and symptom severity scores rated using the Hamilton Depression Rating Scale (HDRS). Samples were analyzed for microRNA expression using microarray and validated using quantitative PCR. As expected, both treatments reduced HDRS scores. Compared with controls, the baseline expression of the microRNA let-7b was less by ~40% in TRD patients compared with controls. The baseline expression of let-7c was also lower by ~50% in TRD patients who received ECT. Bioinformatic analysis revealed that let-7b and let-7c regulates the expression of 27 genes in the PI3k-Akt-mTOR signaling pathway, which has previously been reported to be dysfunctional in depression. The expression of miR-16, miR-182, miR-451 and miR-223 were similar to that in controls. Baseline microRNA expression could not predict treatment response and microRNAs were unaffected by treatment. Taken together, we have identified let-7b and let-7c as candidate biomarkers of major depression.en
dc.description.sponsorshipBrain and Behavior Research Foundation (NARSAD Young Investigator Grant no. 20771); Science Foundation Ireland (02/CE/B124); Health Research Board (HRB: HRA_POR/2012/32)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide862en
dc.identifier.citationGururajan, A., Naughton, M. E., Scott, K. A., O'Connor, R. M., Moloney, G., Clarke, G., Dowling, J., Walsh, A., Ismail, F., Shorten, G., Scott, L., McLoughlin, D. M., Cryan, J. F. and Dinan, T. G. (2016), 'MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c', Translational Psychiatry, 6(8), e862. (9pp.) DOI: 10.1038/tp.2016.131en
dc.identifier.doi10.1038/tp.2016.131en
dc.identifier.eissn2158-3188
dc.identifier.endpage9en
dc.identifier.issued8en
dc.identifier.journaltitleTranslational Psychiatryen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/8918
dc.identifier.volume6en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Centre for Science Engineering and Technology (CSET)/07/CE/B1368/IE/CSET APC: Alimentary Pharmabiotic Centre - Second Term Funding/en
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::HEALTH/201714/EU/Serotonin and GABA-B receptors in anxiety : from developmental risk factors to treatment./DEVANXen
dc.relation.urihttps://www.nature.com/articles/tp2016131
dc.rights© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectDiagnostic markersen
dc.subjectMolecular neuroscienceen
dc.subjectPsychiatryen
dc.titleMicroRNAs as biomarkers for major depression: A role for let-7b and let-7cen
dc.typeArticle (peer-reviewed)en
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