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

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dc.contributor.author Gururajan, Anand
dc.contributor.author Naughton, Maura
dc.contributor.author Scott, Karen A.
dc.contributor.author O'Connor, R. M.
dc.contributor.author Moloney, Gerard M.
dc.contributor.author Clarke, Gerard
dc.contributor.author Dowling, J.
dc.contributor.author Walsh, A.
dc.contributor.author Ismail, F.
dc.contributor.author Shorten, George
dc.contributor.author Scott, Lucinda V.
dc.contributor.author McLoughlin, D. M.
dc.contributor.author Cryan, John F.
dc.contributor.author Dinan, Timothy G.
dc.date.accessioned 2019-10-30T06:13:18Z
dc.date.available 2019-10-30T06:13:18Z
dc.date.issued 2016-08-02
dc.identifier.citation Gururajan, 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.2016.131 en
dc.identifier.volume 6 en
dc.identifier.issued 8 en
dc.identifier.startpage 1 en
dc.identifier.endpage 9 en
dc.identifier.uri http://hdl.handle.net/10468/8918
dc.identifier.doi 10.1038/tp.2016.131 en
dc.description.abstract There 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.sponsorship Brain 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.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Nature Publishing Group en
dc.relation.uri https://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.uri http://creativecommons.org/licenses/by/4.0/ en
dc.subject Diagnostic markers en
dc.subject Molecular neuroscience en
dc.subject Psychiatry en
dc.title MicroRNAs as biomarkers for major depression: A role for let-7b and let-7c en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother John Cryan, Department of Anatomy and Neuroscience and APC Microbiome Institute, University College Cork, Cork, Ireland. +353-21-490-3000 Email:j.cryan@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder Health Research Board en
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Seventh Framework Programme en
dc.contributor.funder Brain and Behavior Research Foundation en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Translational Psychiatry en
dc.internal.IRISemailaddress j.cryan@ucc.ie en
dc.identifier.articleid e862 en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/ en
dc.relation.project info: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.project info:eu-repo/grantAgreement/EC/FP7::SP1::HEALTH/201714/EU/Serotonin and GABA-B receptors in anxiety : from developmental risk factors to treatment./DEVANX en
dc.identifier.eissn 2158-3188


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© 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/. Except where otherwise noted, this item's license is described as © 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/.
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