Gene expression of circadian genes and CIART in bipolar disorder: A preliminary case-control study

Abstract

Based on the observed circadian rhythms disruptions and sleep abnormalities in bipolar disorders (BD), a chronobiological model has been proposed suggesting that core clock genes play a central role in the vulnerability to the disorder. In this context, the analysis of circadian genes expression levels is particularly relevant, however studies focused on the whole set of core clock genes are scarce. We compared the levels of expression of 19 circadian genes (including the recently described circadian repressor (CIART)) in 37 euthymic individuals with BD and 20 healthy controls (HC), using data obtained by RNA sequencing of lymphoblastoid cell lines and validated the results using RT-qPCR. RNA sequencing data showed that CIART gene expression was correlated with those of ARNTL, ARNTL2, DBP, PER2 and TIMELESS. Data from RNA sequencing showed that the level of expression of four circadian genes (ARNTL, ARNTL2, BHLHE41 and CIART) discriminated individuals with BD from HC. We replicated this result using RT-qPCR for ARNTL and CIART. This study suggests that an imbalance between activation/repression of the transcription within the circadian system in individuals with BD as compared to HC and as such opens avenues for further research in larger independent samples combining both expression and epigenetic analyses.

Keywords: Bipolar disorder; CIART; Circadian; Gene expression; Polymerase chain reaction; RNA sequencing.