The bipolarity of light and dark: A review on Bipolar Disorder and circadian cycles

- Changes in circadian function can predict a mood episode recurrence. Abnormal circadian rhythms are ubiquitous in Bipolar Disorder, even during the euthymic phase, with altered melatonin, cortisol, body temperature and locomotor activity cycles.
- The cumulative effect of changes in clock genes has been increasingly accepted as a causal factor of Bipolar Disorder.
- Disturbances of sleep are pervasive in Bipolar Disorder, worse during mood episodes, but still present during euthymic periods.
- It has been documented a relationship between the evening chronotype and Bipolar Disorder.
- Chronotherapeutics is based on circadian rhythms stabilization, controling the individual's exposure to environmental stimuli that act on biological rhythms. It has been demonstrated its efficacy in Bipolar Disorder treatment.

BackgroundBipolar 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.MethodsIt 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.ResultsSeveral 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.LimitationsThis review provides a summary of an extensive research for the relevant literature on this theme, not a patient-wise meta-analysis.ConclusionsIn 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.