title: [Circadian markers and genes in bipolar disorder].
abstract: BACKGROUND
  Bipolar disorder is a severe and complex multifactorial disease, characterized by alternance of acute episodes of depression and mania/hypomania, interspaced by euthymic periods. The etiological determinants of bipolar disorder yet, are still poorly understood. For the last 30 years, chronobiology is an important field of investigation to better understand the pathophysiology of bipolar disorder.
  
  
  METHODS
  We conducted a review using Medline, ISI Database, EMBase, PsyInfo up to January 2015, using the following keywords combinations: "mood disorder", "bipolar disorder", "depression", "unipolar disorder", "major depressive disorder", "affective disorder", for psychiatric conditions; and "circadian rhythms", "circadian markers", "circadian gene", "clock gene", "melatonin" for circadian rhythms. The search critera was presence of word in any field of the article.
  
  
  RESULTS
  Quantitative and qualitative circadian abnormalities are associated with bipolar disorders both during acute episodes and euthymic periods, suggesting that these altered circadian rhythms may represent biological trait markers of the disorder. These circadian dysfunctions were assessed by various validated tools including polysomnography, actigraphy, sleep diaries, chronotype assessments and blood melatonin/cortisol measures. Other altered endogenous circadian activities have also been reported in bipolar patients, such as hormones secretion, core body temperature or fibroblasts activity. Moreover, these markers were also altered in healthy relatives of bipolar patients, suggesting a degree of heritability. Several genetic association studies have also showed associations between multiple circadian genes and bipolar disorder, such as CLOCK, ARTNL1, GSK3β, PER3, NPAS2, NR1D1, TIMELESS, RORA, RORB, and CSNK1ε. Thus, these circadian gene variants may contribute to the genetic susceptibility of the disease. Furthermore, the study of the clock system may help to better understand some phenotypic aspects like the mechanisms of pharmacological treatments used in bipolar disorder, in particular lithium carbonate.
  
  
  CONCLUSIONS
  Several clinical, physiological and genetic data suggest that circadian rhythms dysregulations are involved in the pathophysiology of bipolar disorder. The circadian model has led to the development of new therapeutic strategies such as chronotherapeutics or Inter Personal Social and Rhythms Therapies. Further studies are needed in this promising research field to keep exploring the relationship between these circadian markers, genes and the clinical aspects of the disease.
authors.affiliation: Inserm, U1144, Paris, F-75006, France; Université Paris Descartes, UMR-S1144, Paris, F-75006, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S1144, Paris, F-75013, France; AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris Cedex 10, France.
authors.forename: S
authors.initials: S
authors.lastname: Yeim
authors.affiliation: Pôle de Psychiatrie, Hôpital Henri Mondor -Albert Chenevier, Créteil, 94000, France; Inserm, U955, Créteil, 94000, France; Fondation Fondamental, Créteil, France.
authors.forename: C
authors.initials: C
authors.lastname: Boudebesse
authors.affiliation: Pôle de Psychiatrie, Hôpital Henri Mondor -Albert Chenevier, Créteil, 94000, France; Inserm, U955, Créteil, 94000, France; Fondation Fondamental, Créteil, France.
authors.forename: B
authors.initials: B
authors.lastname: Etain
authors.affiliation: Inserm, U1144, Paris, F-75006, France; Université Paris Descartes, UMR-S1144, Paris, F-75006, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S1144, Paris, F-75013, France; AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris Cedex 10, France; Fondation Fondamental, Créteil, France. Electronic address: frank.bellivier@inserm.fr.
authors.forename: F
authors.initials: F
authors.lastname: Belliviera
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology*; D021081:Chronobiology Disorders / Q000503:physiopathology; D002940:Circadian Rhythm / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008550:Melatonin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008550:Melatonin
keywords: Biomarkers; Biomarqueurs; Bipolar disorders; Chronotype; Circadian genes; Circadian rhythms; Gènes circadiens; Rythmes circadiens; Trouble bipolaire