A new approach to understanding the impact of circadian disruption on human health

Abstract

Background: Light and dark patterns are the major synchronizer of circadian rhythms to the 24-hour solar day. Disruption of circadian rhythms has been associated with a variety of maladies. Ecological studies of human exposures to light are virtually nonexistent, however, making it difficult to determine if, in fact, light-induced circadian disruption directly affects human health.

Methods: A newly developed field measurement device recorded circadian light exposures and activity from day-shift and rotating-shift nurses. Circadian disruption defined in terms of behavioral entrainment was quantified for these two groups using phasor analyses of the circular cross-correlations between light exposure and activity. Circadian disruption also was determined for rats subjected to a consistent 12-hour light/12-hour dark pattern (12L:12D) and ones subjected to a "jet-lagged" schedule.

Results: Day-shift nurses and rats exposed to the consistent light-dark pattern exhibited pronounced similarities in their circular cross-correlation functions and 24-hour phasor representations except for an approximate 12-hour phase difference between species. The phase difference reflects the diurnal versus nocturnal behavior of humans versus rodents. Phase differences within species likely reflect chronotype differences among individuals. Rotating-shift nurses and rats subjected to the "jet-lagged" schedule exhibited significant reductions in phasor magnitudes compared to the day-shift nurses and the 12L:12D rats. The reductions in the 24-hour phasor magnitudes indicate a loss of behavioral entrainment compared to the nurses and the rats with regular light-dark exposure patterns.

Conclusion: This paper provides a quantitative foundation for systematically studying the impact of light-induced circadian disruption in humans and in animal models. Ecological light and activity data are needed to develop the essential insights into circadian entrainment/disruption actually experienced by modern people. These data can now be obtained and analyzed to reveal the interrelationship between actual light exposures and markers of circadian rhythm such as rest-activity patterns, core body temperature, and melatonin synthesis. Moreover, it should now be possible to bridge ecological studies of circadian disruption in humans to parametric studies of the relationships between circadian disruption and health outcomes using animal models.

Figure 1

Daysimeter and functional block diagram.

Figure 2

Spectral response graph. Spectral response functions generated from the model of human circadian phototransduction by Rea et al. [22]. The dashed line represents the predicted spectral response function for an equal energy spectrum light source. The continuous line represents the predicted spectral responses to individual, narrow-band light sources. The two sets of symbols represent empirical spectral response data from two independent laboratories [34, 35].

Figure 3

Logistic transfer function graph. Logistic transfer function relating nocturnal melatonin suppression to the rectified circadian light stimulus (CS) from the model of human circadian phototransduction by Rea et al. [22]. Data from several studies using both narrow-band [34, 35] and polychromatic light sources [36–38] to induce nocturnal melatonin suppression were plotted as a function of CS. A logistic function from Zeitzer et al. [23] was used to fit the data yielding a regression coefficient (r²) for the transfer function equal to 0.82. Figure was adapted from Rea et al. [22].

Figure 4

Activity and light exposure graphs: Nurses. Activity and light exposure data plotted as a function of elapsed number of days for a day-shift nurse (4a, 4c) and for a rotating-shift nurse (4b, 4d). Data collection started at a different clock time for each subject, so each "day" is a different 24-hour period of time for each subject. Circadian light stimulus (CS) exposures were measured with the Daysimeter [20], and transformed to range between the limits of human melatonin suppression (CS Logistic) shown in Figure 3.

Figure 5

Activity and light exposure graphs: Rats. Activity and light exposure data plotted as a function of elapsed time (days) for a 12L:12D rat (5a, 5c) and for a "jet lagged" rat (5b, 5d). At the start of the experiment, the photoperiods were in phase. In the first two days of the experiment, the photoperiods for both groups were the same. Wheel-running data were not collected until the third day of the study, by which time the photoperiod for the "jet-lagged" group had reversed. Most of the activity in the "jet-lagged" group on that day occurred during the light phase.

Figure 6

Behavioral entrainment-correlation functions. Behavioral entrainment-correlation functions relating activity and light exposures for two example nurses, one day-shift nurse (Figure 6a) and one rotating-shift nurse (6b) and two example rats, a rat exposed to a regular 12L:12D pattern of light and dark (6c) and a "jet-lagged" rat exposed to a 12:12 light-dark cycle that was phase-reversed every 48 hours (6d).

Figure 7

Phasor diagrams for day-shift and rotating-shift nurses and for 12L:12D and "jet-lagged" nocturnal rats.

Figure 8

Mean phasors for nurses and for rats.

Figure 9

Phasor magnitudes for the day-shift, and rotating-shift nurses (a) and for the two groups of rats (b).

Figure 10

Interdaily stability (IS) statistics for the day-shift and rotating-shift nurses (a) and for the two groups of rats (b).