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5. FUTURE RESEARCH QUESTIONS
Collectively, the epidemiological and experimental evidence accu-
mulated thus far presents a compelling case that circadian disruption due
to environmental and genetic means produces a wide variety of adverse
health consequences. For people, the environment is the primary source
of disruption of the circadian clock, although genetic polymorphisms alter-
ing clock function may also affect health. The use of artificial light and
increased globalization facilitate and encourage the modern 24 h lifestyle,
and nontraditional work schedules are becoming increasingly common.
While there has been research into factors that influence worker productiv-
ity, there is comparatively little work exploring the potential short-term and
long-term health consequences of scheduling strategies designed to provide
staffing coverage across the day and night. Thus, there is a need for a better
understanding of the effects of nontraditional schedules and the mechanisms
through which these conditions affect health.
Shift work commonly involves misalignment of the circadian clock rel-
ative to external time, insufficient sleep, suppression of the hormone mela-
tonin, psychosocial stress, and changes in other behavioral health variables
such as feeding behavior, alcohol, and tobacco use. Animal models afford
the opportunity to disentangle these variables in order to identify the relative
consequences of each for specific health outcomes. For example, increased
light exposure in mice can induce sleep 422 rather than produce sleep depri-
vation, thus enabling the results to distinguish between circadian- versus
sleep-related mechanisms. Similarly, most mouse strains lack the enzymes
required to synthesize melatonin, 423 but express functional receptors for this
hormone. Furthermore, mice can be exposed to schedules that impose cir-
cadian disruption without inducing a stress response or changes in anxiety or
depressive behavior, 77,353 although this may be schedule-specific. 56 Thus,
the nocturnal mouse presents a useful model to further explore the contri-
bution of circadian disruption per se .
The severity of health consequences across different work and light
schedules remains a major outstanding question. It has been difficult to dif-
ferentiate different types of shift schedules in epidemiological studies to date,
thus the relative consequences of various shift work paradigms on sleep, cog-
nitive, and health factors remain poorly understood. 424-426 Shift work can
be fixed or rotating, with rotating shift work in the forward- (delaying)
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