Alfred Lewy and his colleagues in the OHSU Sleep and Mood Disorders Lab set out to test the hypothesis that circadian physiological rhythms become misaligned with the sleep/wake cycle during the short days of winter, causing some people to become depressed.
Usually these rhythms track to the later dawn in winter, resulting in a circadian phase delay with respect to sleep similar to what happens flying westward. Some people appear to be tracking to the earlier dusk of winter, causing a similar amount of misalignment but in the phase-advance direction. Symptom severity in patients with seasonal affective disorder correlated with the misalignment in either direction.
Recent research suggests that every cell in the body actually has its own clock–liver cells prepare for digestion at particular times of day; patterns of hormone production and brain activity exhibit cyclic peaks and valleys, says Siegelmann.
“The circadian system is really fundamental, it affects our behavior, our physiology and emotions,” she says. “The clock organizes the whole body into a very nice dance, and it organizes people together into a larger social orchestra.”
The so-called “local clocks” have natural circadian cycles that range from 21 to 26 hours, says Siegelmann. They are synchronized by the SCN, but the pathways and mechanisms by which this coordination happens aren’t fully understood. Evidence has recently emerged that the SCN itself is compartmentalized. One clump of cells responds to and processes information about light, they then alert an intermediate group of cells that transmit the information to more peripheral components.
This hierarchy within the circadian system introduces a time-delay in getting the entire body adjusted to a new environment, suggests Siegelmann. The delay is based, in part, on the strength of the connections between the different parts of the SCN, between the SCN and the peripheral clocks, and on the differing rhythms of the local clocks, she says.
To explore the dynamics of the system and how it responds to disruption Siegelmann and Leise designed a model with parameters reflecting this hierarchical nature. The model accounts for the SCN’s light-responsive component, its intermediate component, and the various peripheral components. It incorporates behavioral data, physiological data and what’s known about differences in natural circadian rhythms in the peripheral tissues. In rats, for example, internal organs such as the liver and lungs take a relatively long time to become synchronized with the SCN.
Simulations of the model revealed certain properties about both the stability and adaptability of the system, Siegelmann says. The light sensitive compartment of the master clock responds quickly, providing flexibility, whereas the intermediate compartment of the SCN seems to act as a buffer against small perturbations in the cycle.
The simulations suggest that the system gets most out of whack when the master clock is shifted forward between five and eight hours. After such a large leap, it appears that the master clock actually overshoots the desired time. Then, following a slight delay, the intermediate component and some of the peripheral components overshoot as well, depending on their inherent circadian time and their connectivity with the master clock. For example, the peripheral components that already tend to lag actually try to catch up by backtracking, achieving a leap forward of six hours by delaying themselves 18 hours.