Health Consequences of Circadian Disruption in Humans and Animal Models - Progress in Molecular Biology and Translational Science - page 287

dictated by the circadian system of individuals with an early or late chro-
notype (i.e., morning larks and evening owls, respectively). 22
3.1.3 Non-24 h sleep:wake disorder
Non-24 h sleep:wake disorder occurs when people fail to synchronize with
the external light:dark (LD) cycle and instead “free-run” with an inherent
period different from 24 h. 23 Since the daily rhythms of these people get
progressively earlier or later each day, this results in intermittent mis-
alignment between internal timing and external conditions. Non-24 h
sleep:wake disorder occurs most often in individuals who lack photic input
to the SCN, 24 but has been documented to occur in sighted individuals as
well. 25 Patients with non-24 h sleep:wake disorder may be able to maintain a
fixed diurnal schedule of wakefulness but experience cyclical patterns of day-
time sleepiness and nighttime alertness, along with psychiatric symptoms and
cognitive deficits. 23,26
3.2. Models of circadian disruption in humans and animals
3.2.1 Simulated shift work
To simulate shift work, people can be brought into the laboratory and
engaged in low-stress activities during nighttime hours to maintain wakeful-
ness for several days or allowed to return home during daytime hours. 27,28
In nocturnal rodent models, rotating shift work has been simulated through
the use of repeated shifts of the LD cycle (see later), whereas static night shift
work has been simulated by imposing diurnal work schedules using running
wheels, restricted food access, or operant training protocols. 29-31 In addition
to producing an overt misalignment with the external environment, these
protocols may also alter the temporal relationship between the SCN and
peripheral tissues. 32,33
3.2.2 Simulated jetlag
Simulated jetlag in humans and rodents is typically produced by shifting the
LD cycle by 4-11 h in either an eastward direction (advance) or a westward
direction (delay). Advances of the LD cycle typically require more time for
adjustment in humans 34 and rodent models. 35,36 A 12 h shift of the LD cycle
causes a complete inversion and commonly elicits resynchronization in the
delay direction, but this may vary by species and individual. Research has
uncovered that simulated jetlag produces various forms of circadian disrup-
tion, including a transient misalignment between the internal and external
milieus, 21 misalignment among different tissues comprising the circadian