MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c
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 abilit...
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| Format: | Online |
| Language: | English |
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Nature Publishing Group
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5022079/ |
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pubmed-50220792016-09-19 MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c 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 Dinan, T G Original Article 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. Nature Publishing Group 2016-08 2016-08-02 /pmc/articles/PMC5022079/ /pubmed/27483380 http://dx.doi.org/10.1038/tp.2016.131 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ 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/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
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 Dinan, T G |
| spellingShingle |
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 Dinan, T G MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c |
| author_facet |
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 Dinan, T G |
| author_sort |
Gururajan, A |
| title |
MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c |
| title_short |
MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c |
| title_full |
MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c |
| title_fullStr |
MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c |
| title_full_unstemmed |
MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c |
| title_sort |
micrornas as biomarkers for major depression: a role for let-7b and let-7c |
| description |
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. |
| publisher |
Nature Publishing Group |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5022079/ |
| _version_ |
1613650854876807168 |