title: The bipolarity of light and dark: A review on Bipolar Disorder and circadian cycles.
abstract: BACKGROUND
  Bipolar Disorder is characterized by episodes running the full mood spectrum, from mania to depression. Between mood episodes, residual symptoms remain, as sleep alterations, circadian cycle disturbances, emotional deregulation, cognitive impairment and increased risk for comorbidities. The present review intends to reflect about the most recent and relevant information concerning the biunivocal relation between bipolar disorder and circadian cycles.
  
  
  METHODS
  It was conducted a literature search on PubMed database using the search terms "bipolar", "circadian", "melatonin", "cortisol", "body temperature", "Clock gene", "Bmal1 gene", "Per gene", "Cry gene", "GSK3β", "chronotype", "light therapy", "dark therapy", "sleep deprivation", "lithum" and "agomelatine". Search results were manually reviewed, and pertinent studies were selected for inclusion as appropriate.
  
  
  RESULTS
  Several studies support the relationship between bipolar disorder and circadian cycles, discussing alterations in melatonin, body temperature and cortisol rhythms; disruption of sleep/wake cycle; variations of clock genes; and chronotype. Some therapeutics for bipolar disorder directed to the circadian cycles disturbances are also discussed, including lithium carbonate, agomelatine, light therapy, dark therapy, sleep deprivation and interpersonal and social rhythm therapy.
  
  
  CONCLUSIONS
  This review provides a summary of an extensive research for the relevant literature on this theme, not a patient-wise meta-analysis.
  
  
  CONCLUSIONS
  In the future, it is essential to achieve a better understanding of the relation between bipolar disorder and the circadian system. It is required to establish new treatment protocols, combining psychotherapy, therapies targeting the circadian rhythms and the latest drugs, in order to reduce the risk of relapse and improve affective behaviour.
authors.affiliation: Department of Psychiatry and Mental Health, Centro Hospitalar do Tâmega e Sousa, Penafiel, Portugal. Electronic address: taniacoelhoabreu@gmail.com.
authors.forename: T
authors.initials: T
authors.lastname: Abreu
authors.affiliation: Psychiatry and Mental Health Clinic, Centro Hospitalar São João, and Department of Clinical Neurosciences and Mental Health, Porto Medical School, Porto, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Bragança
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000339:Affect; D018692:Antimanic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D002940:Circadian Rhythm; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D008027:Light; D016651:Lithium Carbonate / Q000627:therapeutic use; D008550:Melatonin; D010789:Phototherapy; D012890:Sleep; D012892:Sleep Deprivation / Q000188:drug therapy; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D018692:Antimanic Agents; D006993:Hypnotics and Sedatives; D016651:Lithium Carbonate; D008550:Melatonin; C084711:agomelatine; D009281:Naphthalenes
keywords: Bipolar disorder; Chronotherapeutics; Chronotype; Circadian cycles; Clock genes; Sleep/wake cycle