Probing the mechanisms of chronotype using quantitative modeling

The physiological mechanisms underlying interindividual differences in chronotype have yet to be established, although evidence suggests both circadian and homeostatic processes are involved. A physiologically based model is developed by combining models of the sleep-wake switch and circadian pacemaker, providing a means of examining how interactions between these systems affect chronotype. Specifically, chronotype is shown to depend on the relative influences of homeostatic and circadian drives, with a stronger homeostatic drive causing morningness. Changes to intrinsic circadian and homeostatic properties, including homeostatic clearance and production rates, and circadian period and amplitude, are also shown to affect chronotype. These results provide a framework for explaining several experimentally observed phenomena, including age-related morningness, adolescent eveningness, and familial advanced and delayed sleep-phase disorders. Additionally, experimental studies have shown that healthy adults on the extremes of the morningness-eveningness spectrum fall into two subtypes: those whose circadian phase markers are unaffected by chronotype, and those whose circadian phase markers track their chronotype. The model demonstrates that this spectrum likely results from interindividual differences in homeostatic kinetics in the first group, and differences in circadian period in the second group. Physiologically based modeling can thus guide diagnosis of sleep pathologies.