Published in

Taylor and Francis Group, The World Journal of Biological Psychiatry, 8(19), p. 619-632, 2017

DOI: 10.1080/15622975.2017.1282174

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Lithium response in bipolar disorders and core clock genes expression.

This paper is available in a repository.
This paper is available in a repository.

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Data provided by SHERPA/RoMEO

Abstract

Objectives: We examine if the lithium response is associated with changes in core clock genes expressions. Methods: The effect of a therapeutic concentration of lithium (1mM) on the expression levels of 17 circadian genes, was examined in lymphoblastoid cell lines (LCLs) derived from two well-characterized groups of BD patients, defined as lithium non-responders (NR, n = 20) or excellent responders (ER, n = 16). Quantitative real-time PCR (qRT-PCR) were conducted at 2, 4 and 8 days (d2, d4, d8) with and without lithium exposure. Results: At d2, in ER only, BHLHE41, RORA, PER1, ARNTL, CRY2, BHLHE40, and CSNK1D were upregulated, whereas NR1D1 was downregulated. At d4, in ER only, CRY1 was downregulated. At d8, in NR only, GSK3β was upregulated and DBP, TIMELESS and CRY1 were downregulated. Significant Group×Lithium interactions existed for NR1D1 at d2 (p = 0.02), and CRY1 at d4 (p = 0.02). Longitudinal analyses showed differential temporal evolutions between NR and ER (significant Time×Group interaction) for PER3, NR1D1, DBP, RORA, CSNK1D, and TIMELESS ; and a significant Time×Lithium interaction for NR1D1 . Co-expression data analyses suggested distinct groups of circadian genes concurrently modulated by lithium. Conclusions: In LCLs, lithium influences circadian genes expressions with differences in amplitude and kinetics according to the patient’s lithium response status.