Each of these pathways has been linked to sleep, and they are slowly being implicated in setting the parameters of the molecular clock.14, 15 Moreover, there have now been over 50 human genetics studies linking polymorphisms in circadian genes with bipolar disorder, including CLOCK and others.16 The pleiotropic effects of these genes may explain the heterogeneity of the disorder in addition to the physical disease comorbidity. This evidence concerns the gene CLOCK and bipolar disorder.