Circadian Rhythms, Sleep Deprivation, and Human Performance - Progress in Molecular Biology and Translational Science - page 169

3111C allele of the CLOCK gene 5 0 -UTR region also has been related to
DSPD. 131 In addition, a specific haplotype of PER3 , which includes the
polymorphism G647, is associated positively with DSPD, 142 while the
N408 allele of casein kinase I epsilon protects against DSPD in a Japanese
population 156 but not in a Brazilian population. 157
ASPD is a rarer disorder than DSPD and is characterized by 3- to 4-h
advanced sleep onsets and wake times relative to desired, normal
times. 152,158 It may be associated with a shorter-than-normal tau (e.g.,
< 24 h). 159 In one study, ASPD was shown to be associated with a mutation
in PER2 , 160 although a later study failed to replicate this finding. 161 Another
report implicated mutations in casein kinase I delta in ASPD. 162 Future stud-
ies on additional core clock genes are needed to determine other mutations
that may underlie this disorder.
Morningness-eveningness and differences in circadian phase preference
are reflected in the diurnal time course of neurobehavioral variable s 163 —
some people perform consistently better in the morning, whereas others
are more alert and perform better in the evening.
How genetic variants underlying morningness-eveningness and chro-
notype disorders affect performance and alertness under normal and
sleep-deprived conditions remains an emerging and important field of inves-
tigation. Two studies have shown that the longer, 5-repeat allele of
the VNTR polymorphism in PER3 , a clock gene linked to diurnal prefer-
ence and DSPD, may be associated with higher sleep propensity both at
baseline and after total sleep deprivation, and worse cognitive performance
following sleep loss. 143,144 However, a study from our laboratory found that
this polymorphism related to individual differences in sleep homeostatic
responses, but not performance responses to chronic sleep restriction. 148
The role of other core clock gene polymorphisms in response to total sleep
deprivation or chronic sleep restriction remains unknown.
A number of core clock genes have been associated with interindividual
differences in diurnal preference or its extreme variants. This area of research
has promising implications for objectively detecting differential vulnerability
to circadian disorders and lifestyles that adversely affect alertness, perfor-
mance and sleep duration, and homeostasis.
6. SLEEP DEPRIVATION AND PERFORMANCE
Sleep deprivation induces a variety of physiological and neuro-
behavioral changes. 164 Both objective and subjective measures of sleep