Molecular insights into human daily behavior.

Human beings exhibit wide variation in their timing of daily behavior. We and others have suggested previously that such differences might arise because of alterations in the period length of the endogenous human circadian oscillator. Using dermal fibroblast cells from skin biopsies of 28 subjects of early and late chronotype (11 "larks" and 17 "owls"), we have studied the circadian period lengths of these two groups, as well as their ability to phase-shift and entrain to environmental and chemical signals. We find not only period length differences between the two classes, but also significant changes in the amplitude and phase-shifting properties of the circadian oscillator among individuals with identical "normal" period lengths. Mathematical modeling shows that these alterations could also account for the extreme behavioral phenotypes of these subjects. We conclude that human chronotype may be influenced not only by the period length of the circadian oscillator, but also by cellular components that affect its amplitude and phase. In many instances, these changes can be studied at the molecular level in primary dermal cells.