Les anomalies des rythmes circadiens occupent actuellement une place importante dans la compréhension de la physiopathologie du trouble bipolaire. Ces anomalies circadiennes sont associées au trouble bipolaire, aussi bien durant les épisodes aigus de dépression et manie, mais également en période euthymique, suggérant leur possible rôle en tant que biomarqueurstraits de la maladie. Ces données ont été mises en évidence à l’aide de divers outils de caractérisation tels que la polysomnographie, l’actigraphie, des questionnaires ainsi que les mesures plasmatiques de différentes hormones telles que la mélatonine, ou encore le cortisol. Certaines de ces anomalies circadiennes sont également observées chez les apparentés sains des patients bipolaires, soulignant leur héritabilité et leur intérêt comme endophénotypes. Diverses études ont de plus montré une association entre plusieurs variants génétiques au sein des gènes circadiens et le trouble bipolaire, pouvant ainsi représenter des facteurs de vulnérabilité au trouble. Enfin, les liens entre trouble bipolaire et système circadien pourraient permettre de mieux comprendre certains aspects de l’expression clinique de la maladie mais aussi d’appréhender les mécanismes physiopathologiques de la maladie ou encore les mécanismes d’action des thymorégulateurs, et particulièrement des sels de Lithium.

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.

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.

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.

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.