A DNA methylation signature discriminates between excellent and non-response to lithium in patients with bipolar disorder type 1.

Scientific Reports
C Marie-ClaireBruno Etain

Abstract

Lithium (Li) is the cornerstone maintenance treatment for bipolar disorders (BD), but response rates are highly variable. To date, no clinical or biological marker is available to reliably define eligibility criteria for a maintenance treatment with Li. We examined whether the prophylactic response to Li (assessed retrospectively) is associated with distinct blood DNA methylation profiles. Bisulfite-treated total blood DNA samples from individuals with BD type 1 (15 excellent-responders (LiERs) versus 11 non-responders (LiNRs)) were used for targeted enrichment of CpG rich genomic regions followed by high-resolution next-generation sequencing to identify differentially methylated regions (DMRs). After controlling for potential confounders we identified 111 DMRs that significantly differ between LiERs and LiNRs with a significant enrichment in neuronal cell components. Logistic regression and receiver operating curves identified a combination of 7 DMRs with a good discriminatory power for response to Li (Area Under the Curve 0.806). Annotated genes associated with these DMRs include Eukaryotic Translation Initiation Factor 2B Subunit Epsilon (EIF2B5), Von Willebrand Factor A Domain Containing 5B2 (VWA5B2), Ral GTPase Activating ...Continue Reading

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Citations

Feb 8, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Huilong LuoXavier Declèves
Apr 4, 2021·Pharmaceuticals·Courtney M VeceraRodrigo Machado-Vieira
Jul 19, 2021·Neuroscience Letters·C Marie-ClaireF Bellivier
Jul 29, 2021·Epigenomics·Hamid Mostafavi AbdolmalekySam Thiagalingam

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Methods Mentioned

BETA
histone acetylation
GTPase
PCR

Clinical Trials Mentioned

NCT02627404

Software Mentioned

Bowtie2
FastQC
metilene
R
LiNR
DAVID
R package mixOmics
LiER
minfi R Bioconductor package
Trimmomatic

Related Concepts

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