Circadian genes and bipolar disorder

Bipolar disorder (BD) is a chronic, potentially disabling illness with a lifetime morbid risk of approximately 1%. There is substantial evidence for a significant genetic etiology, but gene-mapping efforts have been hampered by the complex mode of inheritance and the likelihood of multiple genes of small effect. In view of the complexity, it may be instructive to understand the biological bases for pathogenesis. Extensive disruption in circadian function is known to occur among patients in relapse. Therefore, it is plausible that circadian dysfunction underlies pathogenesis. Evidence for such a hypothesis is mounting and is reviewed here. If circadian dysfunction can be established as an 'endophenotype' for BD, this may not only enable identification of more homogenous sub-groups, but may also facilitate genetic analyses. For example, it would be logical to investigate polymorphisms of genes encoding key proteins that mediate circadian rhythms. Association studies that analyzed circadian genes in BD have been initiated and are reviewed. Other avenues for research are also discussed.