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Methylomic biomarkers of lithium response in bipolar disorder: a clinical utility study

BACKGROUND: Response to lithium (Li) is highly variable in bipolar disorders (BD). Despite decades of research, no clinical predictor(s) of response to Li prophylaxis have been consistently identified. Recently, we developed epigenetic Methylation Specific High-Resolution Melting (MS-HRM) assays abl...

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Autores principales: Marie-Claire, C., Courtin, C., Bellivier, F., Gard, S., Leboyer, M., Scott, J., Etain, B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148930/
https://www.ncbi.nlm.nih.gov/pubmed/37119343
http://dx.doi.org/10.1186/s40345-023-00296-6
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author Marie-Claire, C.
Courtin, C.
Bellivier, F.
Gard, S.
Leboyer, M.
Scott, J.
Etain, B.
author_facet Marie-Claire, C.
Courtin, C.
Bellivier, F.
Gard, S.
Leboyer, M.
Scott, J.
Etain, B.
author_sort Marie-Claire, C.
collection PubMed
description BACKGROUND: Response to lithium (Li) is highly variable in bipolar disorders (BD). Despite decades of research, no clinical predictor(s) of response to Li prophylaxis have been consistently identified. Recently, we developed epigenetic Methylation Specific High-Resolution Melting (MS-HRM) assays able to discriminate good responders (GR) from non-responders (NR) to Li in individuals with BD type 1 (BD-I). This study examined whether a combination of clinical and epigenetic markers can distinguish NR from other types of Li responders. METHODS: We recorded clinical variables that are potentially associated with Li response in 64 individuals with BD-I. MS-HRM assays were performed on DNA isolated from peripheral blood. We used backward stepwise logistic regression analyses, followed by receiver operating characteristic (ROC) curve analysis to estimate the performance of the clinical variables, alone then in combination with the epigenetic biomarkers, to identify GR and partial responders (PaR) vs NR. RESULTS: Polarity at onset, psychotic symptoms at onset and family history of BD classified correctly 70% of individuals according to their Li response (PaR + GR = 86%; NR = 35%). When combined with the epigenetic biomarkers, these three clinical variables plus alcohol misuse (and one DMR: Differentially Methylated Region) correctly classified 86% of individuals, improving the prediction of PaR + GR (93%) and of NR (70%). The ROC analysis demonstrated an improvement in the area under the curve from 0.75 (clinical variables alone) to 0.87 (combination of clinical and epigenetic markers). CONCLUSIONS: Combining clinical predictors and DNA methylation markers of Li response may have greater utility in clinical practice than relying on clinical characteristics alone. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40345-023-00296-6.
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spelling pubmed-101489302023-05-01 Methylomic biomarkers of lithium response in bipolar disorder: a clinical utility study Marie-Claire, C. Courtin, C. Bellivier, F. Gard, S. Leboyer, M. Scott, J. Etain, B. Int J Bipolar Disord Brief Report BACKGROUND: Response to lithium (Li) is highly variable in bipolar disorders (BD). Despite decades of research, no clinical predictor(s) of response to Li prophylaxis have been consistently identified. Recently, we developed epigenetic Methylation Specific High-Resolution Melting (MS-HRM) assays able to discriminate good responders (GR) from non-responders (NR) to Li in individuals with BD type 1 (BD-I). This study examined whether a combination of clinical and epigenetic markers can distinguish NR from other types of Li responders. METHODS: We recorded clinical variables that are potentially associated with Li response in 64 individuals with BD-I. MS-HRM assays were performed on DNA isolated from peripheral blood. We used backward stepwise logistic regression analyses, followed by receiver operating characteristic (ROC) curve analysis to estimate the performance of the clinical variables, alone then in combination with the epigenetic biomarkers, to identify GR and partial responders (PaR) vs NR. RESULTS: Polarity at onset, psychotic symptoms at onset and family history of BD classified correctly 70% of individuals according to their Li response (PaR + GR = 86%; NR = 35%). When combined with the epigenetic biomarkers, these three clinical variables plus alcohol misuse (and one DMR: Differentially Methylated Region) correctly classified 86% of individuals, improving the prediction of PaR + GR (93%) and of NR (70%). The ROC analysis demonstrated an improvement in the area under the curve from 0.75 (clinical variables alone) to 0.87 (combination of clinical and epigenetic markers). CONCLUSIONS: Combining clinical predictors and DNA methylation markers of Li response may have greater utility in clinical practice than relying on clinical characteristics alone. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40345-023-00296-6. Springer Berlin Heidelberg 2023-04-29 /pmc/articles/PMC10148930/ /pubmed/37119343 http://dx.doi.org/10.1186/s40345-023-00296-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Brief Report
Marie-Claire, C.
Courtin, C.
Bellivier, F.
Gard, S.
Leboyer, M.
Scott, J.
Etain, B.
Methylomic biomarkers of lithium response in bipolar disorder: a clinical utility study
title Methylomic biomarkers of lithium response in bipolar disorder: a clinical utility study
title_full Methylomic biomarkers of lithium response in bipolar disorder: a clinical utility study
title_fullStr Methylomic biomarkers of lithium response in bipolar disorder: a clinical utility study
title_full_unstemmed Methylomic biomarkers of lithium response in bipolar disorder: a clinical utility study
title_short Methylomic biomarkers of lithium response in bipolar disorder: a clinical utility study
title_sort methylomic biomarkers of lithium response in bipolar disorder: a clinical utility study
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148930/
https://www.ncbi.nlm.nih.gov/pubmed/37119343
http://dx.doi.org/10.1186/s40345-023-00296-6
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