Sleep- and circadian rhythm-associated pathways as therapeutic targets in bipolar disorder.
BACKGROUND
Disruptions in sleep and circadian rhythms are observed in individuals with bipolar disorders (BD), both during acute mood episodes and remission. Such abnormalities may relate to dysfunction of the molecular circadian clock and could offer a target for new drugs.


METHODS
This review focuses on clinical, actigraphic, biochemical and genetic biomarkers of BDs, as well as animal and cellular models, and highlights that sleep and circadian rhythm disturbances are closely linked to the susceptibility to BDs and vulnerability to mood relapses. As lithium is likely to act as a synchronizer and stabilizer of circadian rhythms, we will review pharmacogenetic studies testing circadian gene polymorphisms and prophylactic response to lithium. Interventions such as sleep deprivation, light therapy and psychological therapies may also target sleep and circadian disruptions in BDs efficiently for treatment and prevention of bipolar depression.


CONCLUSIONS
We suggest that future research should clarify the associations between sleep and circadian rhythm disturbances and alterations of the molecular clock in order to identify critical targets within the circadian pathway. The investigation of such targets using human cellular models or animal models combined with 'omics' approaches are crucial steps for new drug development.
Inserm, U1144 , Paris, F-75006 , France.
Frank
F
Bellivier
Pierre-Alexis
PA
Geoffroy
Bruno
B
Etain
Jan
J
Scott
D000818:Animals; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D021081:Chronobiology Disorders / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics; D015195:Drug Design; D006801:Humans; D018020:Lithium Compounds / Q000494:pharmacology / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012893:Sleep Wake Disorders / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics
D018020:Lithium Compounds
bipolar disorders; circadian rhythm; sleep; therapeutic response