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Circadian abnormalities as markers of susceptibility in bipolar disorders
Vanessa Milhiet1,4,6,Carole Boudebesse1,6,7,Frank Bellivier3,5,6,7,Xavier Drouot2,4,6,Chantal Henry1,4,6,7,Marion Leboyer1,4,6,7,Bruno Etain1,6,7,*
1
AP-HP, Groupe Hospitalier Henri Mondor-Albert Chenevier, Pole de Psychiatrie, Creteil, 94000, France
2
AP-HP, Groupe Henri Mondor-Albert Chenevier, Service de Physiologie, Creteil, 94000, France
3
AP-HP, Groupe Saint-Louis -Lariboisiere -Fernand Widal, Pole Neurosciences, Paris, France
4
Universite Paris Est UPEC, UFR de Medecine, Creteil, 94000, France
5
Universite Paris-7 Paris-Diderot, UFR de Medecine, 75010, Paris, France
6
Inserm, U955, Creteil, 94000, France
7
Fondation Fondamental, Creteil, 94000, France
DOI: 10.2741/S419 Volume 6 Issue 1, pp.120-137
Published: 01 January 2014
(This article belongs to the Special Issue Markers in bipolar disorders)
*Corresponding Author(s):  
Bruno Etain
E-mail:  
bruno.etain@inserm.fr
Abstract

Chronobiological models have contributed to a better understanding of the pathophysiology of bipolar disorders. Circadian functions dysregulations are associated with bipolar disorders, including biochemical (melatonin and cortisol profiles), actigraphic (sleep/wake patterns), and dimensional (chronotypes) circadian markers. These associations are observed not only during acute episodes but also during euthymic periods. Most markers that are associated with bipolar disorders are also found in the healthy relatives of patients, suggesting a strong degree of heritability. As such, they may serve as trait markers of the disorder. Several circadian genes have been found to be associated with bipolar disorders: at least three studies have reported positive associations for each of CLOCK, NPAS2, ARNTL1, NR1D1, PER3, RORB and CSNK1epsilon. Thus the clock machinery may contribute to the genetic susceptibility to bipolar disorders. The circadian model theory has also led to the development of novel therapeutic strategies such as InterPersonal and Social Rhythms Therapy and chronotherapeutics. Additionally, the circadian model theory may help explain how mood stabilizers (in particular lithium carbonate) bring about their therapeutic effects.

Key words

Bipolar disorders, Circadian rhythms, Chronotype, Clock genes, Trait marker, Melatonin, Review

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Vanessa Milhiet, Carole Boudebesse, Frank Bellivier, Xavier Drouot, Chantal Henry, Marion Leboyer, Bruno Etain. Circadian abnormalities as markers of susceptibility in bipolar disorders. Frontiers in Bioscience-Scholar. 2014. 6(1); 120-137.