title: Lithium and bipolar disorder: Impacts from molecular to behavioural circadian rhythms.
abstract: Bipolar disorder (BD) is a severe and common psychiatric disorder. BD pathogenesis, clinical manifestations and relapses are associated with numerous circadian rhythm abnormalities. Lithium (Li) is the first-line treatment in BD, and its therapeutic action has been related to its ability to alter circadian rhythms. We systematically searched the PubMed database until January 2016, aiming to critically examine published studies investigating direct and indirect effects of Li on circadian rhythms. The results, from the 95 retained studies, indicated that Li: acts directly on the molecular clocks; delays the phase of sleep-wakefulness rhythms and the peak elevation of diurnal cycle body temperature; reduces the amplitude and shortens the duration of activity rhythms and lengthens free-running rhythms. Chronic Li treatment stabilizes free-running activity rhythms, by improving day-to-day rhythmicity of the activity, with effects that appear to be dose related. Pharmacogenetics demonstrate several associations of Li's response with circadian genes (NR1D1, GSK3β, CRY1, ARNTL, TIM, PER2). Finally, Li acts on the retinal-hypothalamic pineal pathway, influencing light sensitivity and melatonin secretion. Li is a highly investigated chronobiologic agent, and although its chronobiological effects are not completely understood, it seems highly likely that they constitute an inherent component of its therapeutic action in the treatment of mood disorders.
authors.affiliation: a Inserm , U1144 , Paris , France.|b Université Paris Descartes , UMR-S 1144 , Paris , France.|c Université Paris Diderot , Sorbonne Paris Cité, UMR-S 1144 , Paris , France.
authors.forename: Jeverson
authors.initials: J
authors.lastname: Moreira
authors.affiliation: a Inserm , U1144 , Paris , France.|b Université Paris Descartes , UMR-S 1144 , Paris , France.|c Université Paris Diderot , Sorbonne Paris Cité, UMR-S 1144 , Paris , France.|d AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique , Paris cedex , France.|e Fondation FondaMental , Créteil , France.
authors.forename: Pierre Alexis
authors.initials: PA
authors.lastname: Geoffroy
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism; D001519:Behavior / Q000187:drug effects*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008094:Lithium / Q000008:administration & dosage / Q000494:pharmacology*; D008550:Melatonin / Q000494:pharmacology; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D012890:Sleep / Q000187:drug effects* / Q000502:physiology
chemical_list: D056930:ARNTL Transcription Factors; D008094:Lithium; D008550:Melatonin
keywords: Biological clocks; bipolar disorder; chronobiology; circadian rhythm; lithium; sleep disorders