title: Lithium response in bipolar disorders and core clock genes expression.
abstract: We examine whether the lithium response is associated with changes in the expression of core clock genes.
  
  
  
  The effect of a therapeutic concentration of lithium (1 mM) on the expression levels of 17 circadian genes was examined in lymphoblastoid cell lines (LCLs) derived from two well-characterized groups of bipolar disorder patients, defined as lithium non-responders (NR, n = 20) or excellent responders (ER, n = 16). Quantitative real-time PCR (qRT-PCR) was conducted at 2, 4 and 8 days (d2, d4 and d8) with and without lithium exposure.
  
  
  
  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. Coexpression data analyses suggested distinct groups of circadian genes concurrently modulated by lithium.
  
  
  
  In LCLs, lithium influences expression of circadian genes with differences in amplitude and kinetics according to the patient's lithium response status.
authors.affiliation: a Inserm U1144 , Paris , France.|b Université Paris Diderot , Sorbonne Paris Cité, UMR-S 1144 , Paris , France.|c AP-HP, GH Saint-Louis-Lariboisière-F. Widal , Pôle de Psychiatrie et de Médecine Addictologique , Paris , France.|d Fondation FondaMental , Créteil , France.
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Geoffroy
authors.affiliation: a Inserm U1144 , Paris , France.|e Université Paris Descartes , UMR-S 1144 , Paris , France.|f Laboratoire de biomathématiques, Faculté de pharmacie de Paris Université Paris Descartes , Paris , France.|g Département de biostatistiques et d'informatique médicales , Hôpital Saint-Louis, APHP , Paris , France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Curis
authors.affiliation: a Inserm U1144 , Paris , France.|e Université Paris Descartes , UMR-S 1144 , Paris , France.
authors.forename: Cindie
authors.initials: C
authors.lastname: Courtin
authors.affiliation: a Inserm U1144 , Paris , France.|e Université Paris Descartes , UMR-S 1144 , Paris , France.
authors.forename: Jeverson
authors.initials: J
authors.lastname: Moreira
authors.affiliation: a Inserm U1144 , Paris , France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Morvillers
authors.affiliation: a Inserm U1144 , Paris , France.|b Université Paris Diderot , Sorbonne Paris Cité, UMR-S 1144 , Paris , France.|c AP-HP, GH Saint-Louis-Lariboisière-F. Widal , Pôle de Psychiatrie et de Médecine Addictologique , Paris , France.|d Fondation FondaMental , Créteil , France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Etain
authors.affiliation: a Inserm U1144 , Paris , France.|b Université Paris Diderot , Sorbonne Paris Cité, UMR-S 1144 , Paris , France.|e Université Paris Descartes , UMR-S 1144 , Paris , France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Laplanche
authors.affiliation: a Inserm U1144 , Paris , France.|b Université Paris Diderot , Sorbonne Paris Cité, UMR-S 1144 , Paris , France.|c AP-HP, GH Saint-Louis-Lariboisière-F. Widal , Pôle de Psychiatrie et de Médecine Addictologique , Paris , France.|d Fondation FondaMental , Créteil , France.
authors.forename: Frank
authors.initials: F
authors.lastname: Bellivier
authors.affiliation: a Inserm U1144 , Paris , France.|b Université Paris Diderot , Sorbonne Paris Cité, UMR-S 1144 , Paris , France.|e Université Paris Descartes , UMR-S 1144 , Paris , France.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Marie-Claire
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics*; D002460:Cell Line; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D018020:Lithium Compounds / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged
chemical_list: D018692:Antimanic Agents; D056925:Circadian Rhythm Signaling Peptides and Proteins; D018020:Lithium Compounds
keywords: Bipolar disorder; circadian genes; circadian rhythms; clock genes; lithium carbonate