Methylomic biomarkers of lithium response in bipolar disorder: a clinical utility study.
Biomarker
Bipolar disorders
DNA methylation
Lithium
MS-HRM
Transferability
Journal
International journal of bipolar disorders
ISSN: 2194-7511
Titre abrégé: Int J Bipolar Disord
Pays: Germany
ID NLM: 101622983
Informations de publication
Date de publication:
29 Apr 2023
29 Apr 2023
Historique:
received:
27
01
2023
accepted:
14
04
2023
medline:
29
4
2023
pubmed:
29
4
2023
entrez:
29
4
2023
Statut:
epublish
Résumé
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. 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. 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). Combining clinical predictors and DNA methylation markers of Li response may have greater utility in clinical practice than relying on clinical characteristics alone.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
Combining clinical predictors and DNA methylation markers of Li response may have greater utility in clinical practice than relying on clinical characteristics alone.
Identifiants
pubmed: 37119343
doi: 10.1186/s40345-023-00296-6
pii: 10.1186/s40345-023-00296-6
pmc: PMC10148930
doi:
Types de publication
Journal Article
Langues
eng
Pagination
16Subventions
Organisme : Milken Family Foundation
ID : Bipolar Disorder Therapeutic Research grant 2021
Organisme : Inserm Tranfert
ID : CoPoc 2021
Organisme : Université de Paris
ID : IDEX Prematuration 2021
Informations de copyright
© 2023. The Author(s).
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