A molecular perspective of human circadian rhythm disorders.

A large number of physiological variables display 24-h or circadian rhythms. Genes dedicated to the generation and regulation of physiological circadian rhythms have now been identified in several species, including humans. These clock genes are involved in transcriptional regulatory feedback loops. The mutation of these genes in animals leads to abnormal rhythms or even to arrhythmicity in constant conditions. In this view, and given the similarities between the circadian system of humans and rodents, it is expected that mutations of clock genes in humans may give rise to health problems, in particular sleep and mood disorders. Here we first review the present knowledge of molecular mechanisms underlying circadian rhythmicity, and we then revisit human circadian rhythm syndromes in light of the molecular data.