PSYC 380Research Paper Grading RubricStudentCriteriaPoi.docx

PSYC 380
Research Paper Grading Rubric
Student:
Criteria
Points Possible
Points
Earned
Instructor’s Comments
Content/Development
All key elements of the assignment are covered in a substantive
way.
125
Content is comprehensive, accurate, and/or persuasive.
Major points are stated clearly and are supported by
professional literature or logic.
Meaningful use of source material and analytical reasoning to
elaborate upon the topic or theme.
Research is adequate and timely for the topic.
The context and purpose of the writing are clear.

Organization
The introduction provides sufficient background on the topic
and previews major points.
25
Ideas flow in a logical sequence.
The structure of the paper is clear and easy to follow.
The paper’s organization emphasizes the central theme or
purpose.
Paragraph transitions are present, logical, and direct the flow of
thought throughout the paper.
The conclusion logically derives from the paper’s ideas.
The conclusion reviews the major points for the appropriate
audience.

Format
The paper includes a title page, an abstract, 8–10 full pages of
content, and a references page
50
The references page contains at least 5 scholarly sources.
The paper follows current APA format guidelines.
The paper is written in 12-pt. Times New Roman font, is
double-spaced, and has 1” margins.
The work is original, giving credit to all borrowed ideas.
Grammar/Punctuation/Spelling
Rules of grammar, usage, and punctuation are followed.
25
Spelling is correct.
Readability/Style
Sentences are complete, clear, and concise.
25

Sentences are well constructed with consistently strong and
varied structure.
Sentence transitions are present and direct the flow of thought.
Words used are precise and unambiguous.
Total
250
INTRODUCTION
Stress is a complex condition with emotional, cognitive, and
biological factors. Excessive stress causes long- and short-term
disability in the various human systems, and activates the
defense
system of the central nervous system. The stress responses
differ
depending on the type of stress and the individual’s
physiological
responses. These latter responses consist of neuro-endocrine
and
behavioral responses, and include the changes in the activity
and

immune function of the hypothalamo-pituitary-adrenal (HPA)
axis.
Sleep is an important component of human homeostasis.
Sleep disorders are closely associated with significant medical,
psychological and social disturbances. Chronic sleep restriction
is
an increasing problem in many countries. Since the body’s
stress
systems play a critical role in adapting to a continuously
changing
and challenging environment, it is an important question
whether
these systems are affected by sleep loss. The human body
mobilizes
defensive processes in an adaptive effort to maintain
homeostasis.
If these defenses fail, insomnia may occur. Short-term insomnia
is
caused by a change in routine such as psychiatric illness,
disability,
and stress [1].
In the beginning of sleep, the activity of HPA axis is suppressed
continually. In the latter part of sleep, the HPA secretory
activity
incre as es s o it is clos e to t he maximum circ adi an rhyt hm
immediately after waking up, and the prominent activity of the
HPA axis and sympathetic nervous system influences the overall
amount of rapid eye movement (REM) sleep [2]. Therefore, the
rise of adrenocorticotrophic hormone (ACTH) in the morning
is the decisive control factor regulating the end of sleep [3].
The
Stress and Sleep Disorder

Kuem Sun Han1, Lin Kim2 and Insop Shim3*
1College of Nursing, Korea University, Seoul 136-705,
2College of Medicine, Korea University, Seoul 136-705,
3College of Oriental Medicine, Kyung Hee University, Seoul
130-701, Korea
http://dx.doi.org/10.5607/en.2012.21.4.141
Exp Neurobiol. 2012 Dec;21(4):141-150.
pISSN 1226-2560 • eISSN 2093-8144
Review Article
Received November 16, 2012, Accepted December 10, 2012
*To whom correspondence should be addressed.
TEL: 82-2-961-0698, FAX: 82-2-957-0157
e-mail: [email protected]
Copyright © Experimental Neurobiology 2012.
www.enjournal.org
The purpose of this study was to review potential,
physiological, hormonal and neuronal mechanisms that may
mediate the sleep
changes. This paper investigates the literatures regarding the
activity of the hypothalamic-pituitary-adrenal (HPA) axis, one
of the
main neuroendocrine stress systems during sleep in order to
identify relations between stress and sleep disorder and the
treatment
of stress-induced insomnia. Sleep and wakefulness are regulated
by the aminergic, cholinergic brainstem and hypothalamic
systems.
Activation of the HPA and/or the sympathetic nervous systems
results in wakefulness and these hormones including
corticotropin-

releasing hormone (CRH), adrenocorticotropic hormone
(ACTH), cortisol or corticosterone, noradrenaline, and
adrenaline, are
associated with attention and arousal. Stress-related insomnia
leads to a vicious circle by activating the HPA system. An
awareness
of the close interaction between sleep and stress systems is
emerging and the hypothalamus is now recognized as a key
center for
sleep regulation, with hypothalamic neurontransmitter systems
providing the framework for therapeutic advances. An updated
understanding of these systems may allow researchers to
elucidate neural mechanisms of sleep disorder and to develop
effective
intervention for sleep disorder.
Key words: stress, sleep disorders, psychological stress
response
This is an Open Access article distributed under the terms of the
Creative Commons Attribution Non-Commercial License
(http://creativecommons.org/licenses/by-nc/3.0) which permits
unrestricted non-commercial use, distribution, and
reproduction in any medium, provided the original work is
properly cited.
142 www.enjournal.org
http://dx.doi.org/10.5607/en.2012.21.4.141
Kuem Sun Han, et al.
fact that the beginning and end of sleep involve HPA axis
activity
and the close temporal relationship between the axis and sleep

provides a clue to estimate the effects of the stress on sleep.
The immune system is also influential in the relationship bet-
ween stress and sleep. The most important link between the
immune system and sleep is established by the cytokines which
act
as signaling molecules of the immune system such as
interleukin-1
beta (IL-1β), tumor necrosis factor (TNF), and interferon. IL-
1β,
TNF, and interferon are known to participate in the regulation
of sleep [4]. If IL-1β or TNF are injected, non-REM (NREM)
sleep will increase. But, in the absence of these substances,
sleep
is interrupted. IL-1β is also involved with the immune
regulating
feedback chain, which activates the HPA axis, and may be one
pathway involved in the relationship between stress and sleep
[5].
Typically, stress-related insomnia is transient and persists for
only a few days. But, in the clinic setting the real problem is
chronic insomnia, which is also called physiological insomnia.
The stress-diathesis theory of the onset of chronic insomnia
posits
the involvement of a series of steps configured by the
predisposing,
precipitating, and perpetuating factors. A greater understanding
is needed about the progress of insomnia caused by stress,
particularly physiological insomnia.
In this study, the factors involved in sleep and alertness, their
mechanisms of regulation, and the regulatory influences of the
activation of HPA axis on stress-related physiological responses
and changes in immune function on regulating sleep and
alertness

mechanisms were examined. As well, the mechanisms by which
transient insomnia due to stress becomes chronically stabilized
were investigated.
NEURONAL SYSTEMS AND CHEMICALS IN SLEEP AND
WAKING
The arousal system of the brain stem
The brain stem reticular formation has two dorsal pathways:
a pathway towards the thalamus and a pathway towards the
basal forebrain. These pathways activate the cerebral cortex [6].
Glutamate is the most common excitatory neurotransmitter in
the
brain [7] and major function of the reticular formation neurons
is
to activate the sensory-motor, autonomic neuronal, and cerebral
cortex by the secretion of glutamate[8]. The pedunculopontine
tegmental nuclei and the laterodorsal tegmental nuclei
(PPT/LDT)
which release acetylcholine play an important role on
wakefulness
by projecting through the thalamus, hypothalamus, and the basal
forebrain [9]. Cholinergic neurons reciprocally enervate with
the
thalamus, the locus coeruleus (LC), and the raphe nuclei (DRN)
[10]. Experimentally, acetylcholine in the cerebrum prompts
was
reported to be increased during alertness and, more abundantly,
REM sleep [11]. Noradrenergic neurons of the LC spread out
widely to the overall brain, and they activate alertness, followed
by
NREM, with activity being lowest during REM sleep [12].
When
the LC is stimulated, the activity of the cerebral cortex (i.e.,

EEG)
is increased [13], and the changes in the LC activity are
increased
by new stimulation and various stressors. Stress may activate
the LC activity by secretion of corticosteroid releasing hormone
(CRH) in the paraventricular nucleus of the hypothalamus [14].
The nigrostriatal dopaminergic pathway promotes waking in
motor activity, and inhibits sleep [15]. But, the mesocortical
and
mesolimbic dopaminergic neurons in the ventral tegmental area
(VTA) of the midbrain affect the cerebral cortex and the limbic
systems, regulating alertness. Serotonergic neurons of the DRN
are activated during waking state, and are inhibited in REM
sleep
[16]. Serotonergic neurons are involved in the generating of
slow
wave, but are not activated during sleep [17]. The collective
data
to data are consistent with the view that the serotonergic
neurons
are responsible for some of the activating systems, but seem to
reduce the cortex activation by exerting an inhibitory influence
on other neurons responsible for alertness [7]. Serotonin 5-
HT1A
receptors are expressed in the gamma-aminobutyric acid
(GABA)
ergic neurons of the basal forebrain [18]. GABAergic neurons
are hyperpolarized by secreting 5-HT in the DRN. Therefore,
if GABAergic ne urons are in hibite d by 5-HT1A re ce ptor
agonist, then wakefulness can be indirectly caused by increasing
acetylcholine in the cortex.
Hypothalamic arousal systems
When the hypothalamus is stimulated, a series of arousal reac-
tions including the activation of the HPA axis, the cortex, and

the autonomic nervous system are elicited [19]. The posterior
hypothalamus, which is involved in alertness, uses glutamate
as the primary neurotransmitter [20]. The tuberomammillary
neurons (TM) located in the posterior hypothalamus are the only
histamine neurons in the brain; they receive information from
numerous activation-related regions of the brain stem and the
ventrolateral preoptic area (VLPO) [21]. Histamine modulates
to
maintain cortical activity and wakefulness. Orexin, which is
also
called hypocretin, is secreted by neurons in the lateral and
medial
hypothalamus [22]. The orexin neurons project to the cerebral
cortex, and most of arousal regions including monoaminergic
and
cholinergic neurons and connect with the preoptic area (POA)
and BF.
A lack of orexin causes narcolepsy. Orexin is activated in the
alertness condition, and especially plays a role in motor
activity.
The orexin neurons reciprocally project to VLPO neuron, but
there are no orexin receptors in the VLPO [23]. Therefore, the
143www.enjournal.orghttp://dx.doi.org/10.5607/en.2012.21.4.1
41
orexin neurons reinforce alertness, but do not directly suppress
the VLPO, and the asymmetrical relationship seems to
contribute
to make the flip-flop switch stable, which stops conduction
to unwanted sleep. As a result, the activity of the LC, which is

inactivated during REM, is predominated by orexin neurons,
which led to conclusion that orexin is a target for regulating
REM
sleep [24].
POA
The VLPO as a sleep center contains GABAergic/galaninergic
neurons, which act as an inhibitory neurotransmitter. POA neu-
rons principally use histamine, and so assume to be involved in
alertness and NREM [25, 26]. VLPO neurons send terminals
to the DRN and LC, which have important roles for REM.
Conversely, GABAergic neurons in the VLPO are suppressed by
noradrenalin and serotonin [27] and H2 receptors are suppressed
by histamine. c-Fos-immunoreactive neurons (Fos-IRNs) in the
VLPO and median preoptic nucleus (MnPN) have been closely
correlated with existing sleep quantity. In particular, Fos-IRNs
were increased during sleep recovery after sleep deprivation
[28].
These findings show that the VLPOA is a crucial neural
substrate
for sleep promotion. Adenosine promotes sleep by exciting
the neural activity of the POA [27], while on the other hand it
facilitates sleep by suppressing the alertness-activating neurons
such as cholinergic neurons [29].
Cytokines including IL1-β and TNF influence homeostatic
sleep control [30]. TNF-α causes NREM via the POA and the
LC. In experiments with mice, the injection of TNF-α in these
regions resulted in increased NREM, and the LC suppressed
noradrenaline alertness mechanisms. Prostaglandin D2 (PGD2)
is another important endogenous sleep factor that also acts in
the
POA. Growth hormone-releasing hormone (GHRH) also plays
an
important role in the regulation of NREM [30].

THE PROCESS OF SLEEP REGULATION
Schema of a typical entrained 24-hour day
Sleeping involves sufficient periods of wakefulness and decline
of core temperature, which are merged to open the “gate” to
sleep.
The beginning of sleep involves the first circadian vertex of
slow
wave sleep. The pressure of slow wave sleep decreases with
time.
Generally, the vertex of circadian REM can be set between the
half-cycle of two slow wave sleep pressures. To minimize
sleepiness
in the early evening and to maintain proper alertness, three
factors seem to be critical: low pressure of slow wave sleep,
REM-
minimum pressure of sleep, and peak core temperature. Sleep
and
alertness are mutually competitive and necessarily exclusive;
the
development of alertness is the reverse of sleep pressure. In the
late evening core temperature begins to decrease, and
somnolence
related to sustained alertness continuously increases. This cycle
is
repeated thereafter.
Homeostatic process of sleep
Slow wave activity is a physio logical indicator of NREM sleep
homeostasis. Slow wave activity can be considered an indicator
of the depth or intensity of sleep. The stimulus reaction
decreases

depending on the increase of slow wave activity, and this
activity
is inversely correlated with alertness [31]. In addition, the
process
of comprehensive slow wave sleep is high in the beginning of
sleep but decreases gradually thereafter [32]. Spectral analysis
of brainwave activity revealed a change in density of average
brainwave between 0.25-2.0 Hz depending on the process of
sleep
[33]. A nap late in the afternoon includes increased slow wave
sleep than a nap early in the afternoon [34]. Shorter duration of
night-time sleep produces increased slow wave activity in a nap
the next morning [35]. Concerning the effects of sleep
deprivation,
recovery sleep includes increased slow wave sleep following the
deprivation of partial or full sleep [32]. Especially, the increase
of
slow wave sleep is markedly enhanced in the first day of
recovery
sleep, as the extension of alertness period [36].
The immune system is involved with the various stress
responses,
and homeostasis during sleep and generation of NREM. Levels
of TNF and IL1-β in the brain change with time courses; a study
conducted in a mouse model demonstrated high levels of TNF
mRNA and protein in the cortex and hypothalamus when sleep
inclination was maximal. In the study, sleep deprivation was
linked
with an increase in the brain density of cytokine. In addition,
upregulation of cytokine and somnolence was also evident in
mice
challenged with infection. Bacterial cell wall muramyl peptides
and viral double strand RNA [37] reinforce cytokine production,
similar to compounds including IL1-β and TNF. If TNF is
injected in the POA of the hypothalamus, it reinforces REM,

while injections of TNF soluble receptor at the same site spur a
spontaneous decrease in sleep. Injections of IL1-β receptors at
the same site suppress alertness-activating neurons and
stimulate
sleep-activating neurons [30]. TNF or IL1-β reinforces sleep
in these areas as well as in other regions of the brain, if TNF or
IL1-β is injected directly into the cerebral cortex; slow wave
sleep
is increased in the injected half of the brain sphere. Similarly,
injection of TNF soluble receptor or IL1-β soluble receptor
suppressed the increases of slow wave sleep after sleep
deprivation
in the injected half-sphere [38].
Cytokines, especially TNF and IL1-β, act on the sleep control
circuit and are involved with sleep-related morbidity. IL1-β,
IL2,
http://dx.doi.org/10.5607/en.2012.21.4.141
IL6, IL8, IL15, IL18, TNF, fibroblast growth factor, and nerve
growth factor are some of the cytokines that have been shown to
reinforce sleep. But, IL4, IL10, IL13, and insulin-like growth
factor
as among the cytokines that suppress sleep. These sleep
regulatory
substances (SRS) are responsible for some regulatory
mechanisms
that maintain the ark of the cycle of long-lasting sleep/alertness,
and so have been linked to sleep homeostatic mechanisms [30].
After sleep deprivation, the production of interferon (IFN),

TNF,
and IL1-β was increased [37]. Sleep apnea can accompany sleep
deprivation and hypoxia, and involves an increase of TNF [37].
IL1-β and TNF activate nuclear factor-kappa B (NFκB) and
c-Fos (AP-1), transcription factors, and a myriad of short half-
life, small molecules such as activated nitric oxide adenosine,
and
prostaglandins [39]. Adenosine causes NFκB nuclear
translocation
in the basal forebrain. NFκB is activated by sleep deprivation
[40].
Summarizing the molecular connection related to homeostasis
of sleep, SRS including TNF, IL1-β, and NGF are generated or
secreted by neuron throughout the waking period, in a process
that can be affected by stress. SRS production/secretion can
be subject to positive or negative feedback regulation from
transcription factors such as NFκB, cytokines, and hormones.
Cytokine production and activity includes transcription and
detoxification, and their direct actions on sleep were mediated
by
nitric oxide and adenosine, whose short half-lives enable ready
and swift response [5].
Circadian process of sleep
The circadian cycle of physical function continues without
outside temporal clues from the beginning, and it is natural and
that the cycle is precisely 24 hours [35]. People naturally feel
sleepy
at night, due to the fatigue resulting from daily life rather than
the screening of the internal clock, so sleep can be delayed by
appropriate stimuli. As a result, the fact that determination of
sleep
time is changed by the circadian mechanisms in daily life can be
overlooked. Control of circadian rhythm by REM is not related

to sleep time, but the peak REM tendency is coincident with the
peak nadir of body temperature in the early morning.
Somnolence
is regulated by homeostatic and behavioral results, and
circadian
rhythm. The tendency of sleep is consistently high when the
rhythm of human body temperature is disrupted; the result is a
need for sleep in early afternoon (i.e., nap, siesta). This
distribution
reflects the phase of the circadian cycle, which is determined
endogenously.
The suprachiasmatic nucleus (SCN) is the “master clock” of the
brain. SCN neurons are activated in a 24-hour transcription and
detoxification cycle. Animal experiments have demonstrated
that SCN removal abrogates the circadian rhythm of behavioral
and physiological processes, which can prevent sleep [41].
Under
normal circumstances, melatonin in the SCN will be reset every
day by being secreted by the light entering through the eyes in
the
morning and from the pineal at night [42]. The light is detected
by series of ganglion cells equipped with the predisposing
factor
melanopsin, which is delivered to the SCN. Information from
SCN neurons is amplified in the near sub-paraventricular zone
(SPZ) [43]. The neurons from the DMH deliver the information
to neurons responsible for circadian secretion, which regulates
hormones such as orexin neuron related to VLPO and alertness
as central sleep, body temperature and corticosteroids, and
thyrotropin-releasing hormone. Therefore, sleep-wake, activity,
feeding, temperature and corticosteroid rhythms are changed
equivalent to the DMH variable activity [44].
Core temperature is one of the physiological progresses regu-

lated by the circadian pacemaker. Sleep begins when the core
temperature falls from its peak. Sleep ends following the nadir
of core temperature. In addition to the circadian rhythm of core
temperature, one of the important substances involved in the
regulation of sleep-wakefulness rhythm is melatonin. Dim light
melatonin onset (DLMO) begins 2-3 hours before the usual
start time of sleep [45]. The DLMO is relatively less affected by
exogenous factors, so it is recognized as reliable marker to
measure
the circadian rhythm of humans. In addition to melatonin, other
substances involved in regulating the sleep-wakefulness
circadian
rhythm are corticosteroids. Endogenous rhythm influences the
circadian rhythm of HPA secretion through the multi-synaptic
SCN-adrenal pathway [46]. Cortisol secretion is very rhythmic,
and is maintained at a low le vel during the day and at the
beginning of night, but the secretion increases from the latter
part
of the night towards morning. The nadir of cortisol appears
within
2 hours after the start of sleep. In other words, sleep begins
when
cortisol is lowest and finishes when cortisol is highest. Physical
or
physiological stress changes cortisol secretion by activating the
HPA axis.
THEORETICAL MODELS OF INSOMNIA
Stress as a precipitating factor
Post-traumatic stress disorder (PTSD) is an extreme case of
stress-related insomnia, which occurs after traumatic
experiences.
According to Hefez et al. [47], individuals who have
experienced

extremely traumatic events shows more recollection of a dream
with low sleep efficiency. Cartwright and Wood [48] reported
that
sleep can be easily disrupted in people undergoing divorce, with
decreased delta sleep. Kageyama et al. [49] asserted the
relevance
of the subjective quality of reporting between career stress and
41
poor sleep, and Hall et al. [50] opined that stress-related
thinking
is connected with insomnia. Verlander et al. [51] reported that
an
emotional reaction is the best predictor for explaining the
factors
such as depth and quality of sleep among three stress factors:
burden events, personality mediators, and emotion reactions.
Paulsen and Shaver [52] reported that the negative life events
have
indirect effects only, but do affect objective sleep. Cernovsky
[53]
demonstrated that the major stress and sleep obstacles are not
closely correlated, and that the negative life-cycle is somewhat
connected with sleep obstacles among the various sleep factors.
Reynolds et al. [54] reported that REM is increased in the brain
waves of the people who have experienced bereavement, but it
does not affect the rate of sleep efficiency, REM latency, and
delta
sleep.

In the 1980s, the interest in minor stress (i.e., “hassles”) was
heightened by considering coping mechanism of individuals
about
stress or personality of characteristics separate from previous
trends in major stress events such as death and divorce, which
lead to significant changes in life. The daily worry and
frustration
that are a routine occurrence have been proposed as harmful for
individual’s health [55]. Thus, minor stress is a more important
factor than the major stress, can have bigger effects on the
disease
and psychological and physical symptoms, and can be a better
predictor. Hick and Garcia [56] reported that the increasing
stress
lessens the length of sleep. The influence of stress as the trigger
or
influence of insomnia has been inconsistent. However,
according
to the Diagnostic and Statistical Manual of Mental Disorders,
4th edition (DSM-IV), “Most of the insomnia occurs with acute
for psychological, social and medical stress”; in one study, 78%
insomnia patients reported a link between such stresses and
insomnia [57].
In several prospective studies, the main predictors of insomnia
were depression, health problems, physical inability, and mental
and social state [58]. In addition, while stress is acknowledged
as
an important risk factor of insomnia, Morin et al. [59] opined
that
its’ significance differs between the insomnia patients and
affected
individuals concerning an individual’s reaction to the of
frequency
of stress.

Stress and related sleep physiology
Stress activates the sympatho-adreno-medullary (SAM) and
HPA systems, influencing cardiovascular, catecholamine,
cortisol,
ACTH, and CRH hyperactivity [60]. The stress system interacts
by endocrines, the gastrointestinal and immune systems, and
positive/negative feedback pathways [61]. Excessive secretion
of cor tis ol negatively af fects neural str uctures such as t he
hippocampus, resulting in memory deficits [62] and, especially,
negatively influences sleep by affecting the activity of the SAM
and HPA systems [63]. The immune system is also affected by
stress; the autonomic nervous system activates genes involved
in
production of immune substances such as cytokines [64].
Increased activity of the autonomic nervous system [65] and
cortisol causes alertness. Increased ACT influences awakening.
Therefore, awakening from sleep after stress can be related to
the early increase of ACTH [66]. It has been shown that the
injection of ACTH increases sleep latency, decreases slow wave
sleep, and fragments sleep [67]. For example, the receptor
activity
of mineral corticosteroid increases NREM, and the receptor
activity of glucocorticosteroid increases alertness and REM
[66].
In experiments where mice were immobilized or subjected to
social stimulation, decreased slow wave sleep and REM were
documented, and their increase during recover y sleep was
revealed [68]. Acute and chronic stress decreases slow wave
sleep
and REM in mice exposed to stress, but a normal sleep pattern
was
re-established upon recovery. In an acute stress situation, CRH
(an ACTH secretion hormone) mediates the stress reaction in

the
central nervous system [69]. CRH acting as a neurotransmitter
in the LC activates noradrenaline neurons in the LC. But, under
chronic stress, distal corticosteroids increase and sleep is
disrupted.
Therefore, in chronic stress, the reaction of slow wave sleep and
REM is not significant.
The immune system is important in the relationship between
stress and sleep. Acute or chronic stress in humans and animals
considerably affects sleep through the immune system. Acute
stress mainly activates the immune system related to natural
killer (NK) cells mediated by catecholamine [70]. Meanwhile,
chronic stress down-regulates the immune system by decreasing
B and T cells and reducing NK cell activity [71]. This occurs in
depression and PTSD [71]. IL1-β is also involved in an immune
regulated feedback that activates the HPA axis. This is involved
in the relationship between stress and sleep. Blood IL-1β levels
change depending on the cycle of sleep-alertness, and blood
TNF is related to the slow wave activity of brainwaves. Also,
there
is a strong correlation between the degree of the loss of sleep
continuity and NK cell function obstacles [72].
Inversely, insomnia causes physiological responses like those in
stress situations. Sleep increases growth hormone and
testosterone
[73], and reduces metabolism and blood flow, to fight against
stress [74]. In a state of insomnia, cortisol, heart rate, central
temperature, and oxygen consumption are increased [2], as are
glucose tolerance [75] and cytokines [76]. Sleep deprivation
increases ghrelin and decreases leptin, which exacerbates
appetite
[77]. Evidence to date indicates (bit has not confirmed) a close
connection between stress and sleep. Stress causes pyscho-

http://dx.doi.org/10.5607/en.2012.21.4.141
physiological responses and activates the HPA system, which
are
incompatible with normal sleep. Also, insomnia causes a vicious
circle of stress-insomnia by further activating the HPA system.
Especially, chronic stress can cause continuous hippocampus-
related memory system fatigue by up-regulating the HPA
system.
The long-term impacts of chronic stress remain unclear.
Physiological model
Patients with insomnia, despite lacking night sleep and day-
time fatigue, are at a higher state of alertness than those who
have appropriate sleep, which has also been demonstrated by the
fact that patients with insomnia have longer sleep latency than a
control group consisting of ordinary people who sleep upon an
execution of latency repeat inspection. This suggests that
insomnia
is an over-alertness obstacle ranging for 24 hours, and not one
limited only to nighttime [78]. As another piece of evidence of
over-alertness, patients with insomnia have an increased
metabolic
rate for 24 hours, their sympathetic nervous system is relatively
exacerbated [78], and their adrenal cortex hormone and cortisol
density are markedly increased compared to ordinary people [2].
HPA axis activity-related cytokine hypersecretion or daily cycle
fluctuation can explain insomnia-related fatigue and poor sleep.
Also, patients with insomnia have an increased relative rate of
beta-power in brainwaves while awake during the hypnagogic

period in which the delta power declines, which suggests the
alertness of the central nervous system [79]. The nervous
system
circuit interacting through brain imaging techniques plays an
important role for the neuronal physiology of insomnia [80], in
which general alertness system (upturn reticula formation and
hypothalamus), the system that regulates emotions
(hippocampu,
tonsil, anterior cingulate cortex) and cognitive system
(prefrontal
lobe), are involved.
Behavioral model
According to a behavioral model proposed by Spielman et al.
[81], insomnia is presumed to be caused acutely by both consti-
tutional and causal factors. Acute insomnia is gradually and
chro-
nically strengthened and stabilized by a nonadaptive reaction
strategy. In other words, if an insomnia episode begins, patients
choose various nonadaptive strategies intended to produce more
sleep (e.g., spending excessive time in bed and staying awake
in bed for a long time). These behaviors reduce sleep efficiency,
which results in conditioned alertness during usual sleep and the
occurrence of chronic insomnia.
Cognitive model
A cognitive model first proposed by Morin [82] notes that
concern and reflection by early stress disrupts sleep and causes
an acute episode of insomnia. The individual’s reactions to this
transient sleep trouble (i.e., behaviors, beliefs, attitudes, and
interpretations) contribute to sustaining or deteriorating the
subsequent insomnia. Once sleep disturbance begins, concern
and reflection changes from life stress to sleep itself, and with

day-
time symptoms in the absence of sufficient sleep. This negative
cognitive activity is further strengthened if one feels threatened
related to sleep or perceives a lack of sleep [83]. Moreover,
moni-
toring day-time symptoms due to sleep and lack of sleep causes
autonomic neuronal alertness and emotional distress, which
causes selective attention to threatening clues associated with
sleep to sustain insomnia [84]. Such a chain reaction causes a
state of over-alertness, which conflicts with a state of relaxation
needed for inducing sleep. Excessive concern with sleep and
fear
for not having sleep generates bad sleep habits such as taking a
nap or staying in bed for a long time, which collapses the sleep-
alertness cycle and homeostasis of sleep. In a nutshell,
regardless
of the causes of insomnia in an early phase, bad sleep habits and
non-functional recognition of sleep are almost always involved
in
perpetuating or deteriorating sleep obstacles over time [85].
Neurocognitive model
Patients with insomnia tend to overestimate their sleep latency,
while tending to underestimate their overall sleep time (i.e.,
they
say it takes a long time to fall asleep and that they do not sleep
in).
Polysomnogram data indicate wakefulness even if sleep begins,
which prompts awakening. Also, for patients with insomnia,
use of benzodiazepine-based sleeping pills does not normalize
sleep, although patients report more benefits attributed to the
medication than can be explained by objective variables with
improved sleep [86]. Cognitive neural perspective focusing on
cortex alertness measured by brainwave activity allows patients
with insomnia to explain diagnostically the paradox in the

patients [86]. The consistency of the behavioral model is that
the
neuronal cognitive model concerns the view that acute insomnia
is stirred by living stress, while continuous insomnia is caused
by maladjusted countermeasures, and that chronic insomnia
results from conditioned alertness. The difference of the
neuronal
cognitive model on chronic insomnia focuses on cortical
arousal,
a form of conditioned alertness [86]. According to the neuronal
cognitive model, hypnagogue or high frequenc y brainwave
activity at that time is a primary feature of chronic insomnia,
and
conditioned alertness in this form prompts various sensory and
cognitive phenomena that do not occur during quality sleep.
The theoretical model of insomnia is a stress-constitution
model,
which argues that pre-onset predisposing factors, precipitating
41
factors like stress, and subsequent perpetuating factors causes
the
expression of insomnia. In other words, people with insomnia
have a characteristic of the predisposing factors of insomnia,
the precipitating factors including cause an actual artwork, such
acute insomnia is strengthened by nonadaptive reaction strategy
to become chronically stabilized. Physiological, cognitive, and
awakening of intellectual mind, maladjusted behavior, circadian
rhythm, and sleep homeostatic obstacles can be the perpetuating

factors that perpetuate transient insomnia caused by stress.
MANAGING INSOMNIA THROUGH DAILY LIFE STRESS
MA-
NAGEMENT
Insomnia caused by various stress factors can be prevented and
managed by managing everyday life habits. The management
of day-to-day lifestyle can be divided into mental and physical
aspects based on the comprehensive model of stress [87]. As the
management of mental aspect, since the perception and
evaluation
of the factor rather than the event itself significantly affect
stress,
one should make efforts to change his/her cognitive evaluation
to
a more positive one and to reduce everyday life stress. This can
be
accomplished by maintaining the balance between work and rest
by releasing stress at the moment to deal with the stress,
expressing
concerns or problems with the expression of emotional tension,
maintaining an inner balance with reality by accepting what
cannot be changed and accepting what is wrong, trying to plan
and
record a daily routine and form a habit of setting priorities, And
seeking solutions by simplifying the pertinent issue when facing
a
complicated and difficult problem [88].
The management of day-to-day lifestyle in physical aspect
includes regular and balanced meals, Balanced physical activity
by regular moderate motion about for 30 min., 3-4 times a week,
(e.g., stretching, jogging, biking or hiking), and induced body
rest
and relaxation, such as controlled respiration and muscle

tension
methods.
Most of all, goal-setting, continuing to make constant efforts
toward the goals, accepting the fact that no one is perfect, and
doing one’s best can help overcome insomnia caused by stress.
CONCLUSIONS
Excessive stress is detrimental on many levels to humans, and
it activates the defense system of the central nervous system.
Stress-related physiological responses differ depending on each
individual cognitive form, and these physiological responses
cause the neuro-endocrine responses and behavioral responses.
Sleep is an ess enti al biological pro cess for humans. Many
anatomical structures and biochemical substances are involved
in the regulating mechanisms including the HPA axis, which is
activated by the factors including stress and immune function.
The
regulation of sleep is configured with the circadian process that
determines the beginning and ending of sleep, and the
homeostatic
process that maintains the depth and the amount of sleep. In the
early stage of sleep, the activity of HPA axis is suppressed and
ongoing, while in the latter part of sleep HPA secretion activity
increases. The increased HPA axis and activity of the
sympathetic
nervous system influences rapid eye movement (REM) sleep.
Components of immune system including IL-1β are involved
in the homeostatic regulating mechanisms of sleep. In addition,
IL-1β participates in the immune regulating feedback chain that
activates the HPA axis. Stress-related insomnia leads to a
vicious
circle by activating the HPA system. Chronic insomnia, which
is

termed physiological insomnia, is a clinical problem. The
stress-
diathesis theory concerning the onset of chronic insomnia posits
the involvement of a series of factors consisting of
predisposing,
precipitating, and perpetuating factors. Stress-induced insomnia
that becomes chronically stabilized is connected to the
treatment,
so that an understanding of the perpetuating factor is essential.
ACKNOWLEDGEMENTS
This study was supported by a KBSI grant (T31901) to SH.
REFERENCES
1. Partinen M (1994) Sleep disorders and stress. J Psychosom
Res 38 Suppl 1:89-91.
2. Vgontzas AN, Bixler EO, Lin HM, Prolo P, Mastorakos G,
Vela-Bueno A, Kales A, Chrousos GP (2001) Chronic in-
somnia is associated with nyctohemeral activation of the
hypothalamic-pituitary-adrenal axis: clinical implications. J
Clin Endocrinol Metab 86:3787-3794.
3. Weibel L, Follenius M, Spiegel K, Ehrhart J, Brandenberger
G
(1995) Comparative effect of night and daytime sleep on the
24-hour cortisol secretory profile. Sleep 18:549-556.
4. Takahashi S, Kapás L, Fang J, Krueger JM (1999)
Somnogenic
relationships between tumor necrosis factor and interleu-
kin-1. Am J Physiol 276:R1132-R1140.
5. Krueger JM, Rector DM, Churchill L (2007) Sleep and

cytokines. Sleep Med Clin 2:161-169.
6. Steriade M, Oakson G, Ropert N (1982) Firing rates and
patterns of midbrain reticular neurons during steady and
transitional states of the sleep-waking cycle. Exp Brain Res
46:37-51.
http://dx.doi.org/10.5607/en.2012.21.4.141
7. Jones BE (2005) From waking to sleeping: neuronal and
chemical substrates. Trends Pharmacol Sci 26:578-586.
8. Stenberg D (2007) Neuroanatomy and neurochemistry of
sleep. Cell Mol Life Sci 64:1187-1204.
9. McCormick DA (1989) Cholinergic and noradrenergic mo-
dulation of thalamocortical processing. Trends Neurosci
12:215-221.
10. Ford B, Holmes CJ, Mainville L, Jones BE (1995)
GABAergic
ne u ron s i n t he r at p ontome s e nc e p h a l i c te g me
ntu m :
codistribution with cholinergic and other tegmental neurons
projecting to the posterior lateral hypothalamus. J Comp
Neurol 363:177-196.
11. Vazquez J, Baghdoyan HA (2001) Basal forebrain
acetylcho-
line release during REM sleep is significantly greater than
during waking. Am J Physiol Regul Integr Comp Physiol 280:

R598-R601.
12. Chu N, Bloom FE (1973) Norepinephrine-containing neu-
rons: changes in spontaneous discharge patterns during
sleeping and waking. Science 179:908-910.
13. Berridge CW, Foote SL (1991) Effects of locus coeruleus
activation on electroencephalographic activity in neocortex
and hippocampus. J Neurosci 11:3135-3145.
14. Valentino RJ, Foote SL (1988) C orticotropin-releasing
hormone increases tonic but not sensory-evoked activity of
noradrenergic locus coeruleus neurons in unanesthetized
rats. J Neurosci 8:1016-1025.
15. Trulson ME (1985) Activity of dopamine-containing substa-
ntia nigra neurons in freely moving cats. Neurosci Biobehav
Rev 9:283-297.
16. McGinty DJ, Harper RM (1976) Dorsal raphe neurons:
depression of firing during sleep in cats. Brain Res 101:569-
575.
17. Trulson ME, Jacobs BL (1979) Raphe unit activity in freely
moving cats: correlation with level of behavioral arousal.
Brain Res 163:135-150.
18. Lüttgen M, Ogren SO, Meister B (2005) 5-HT1A receptor
mRNA and immunoreactivity in the rat medial septum/
diagonal band of Broca-relationships to GABAergic and
cholinergic neurons. J Chem Neuroanat 29:93-111.
19. Bailey TW, Dimicco JA (2001) Chemical stimulation of the
dorsomedial hypothalamus elevates plasma ACTH in cons-
cious rats. Am J Physiol Regul Integr Comp Physiol 280:R8-
R15.

20. Ziegler DR, Cullinan WE, Herman JP (2002) Distribution of
vesicular glutamate transporter mRNA in rat hypothalamus.
J Comp Neurol 448:217-229.
21. Panula P, Pir vola U, Auvinen S, Airaksinen MS (1989)
Histamine-immunoreactive nerve fibers in the rat brain.
Neuroscience 28:585-610.
22. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM,
Tanaka H, Williams SC, Richardson JA, Kozlowski GP,
Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA,
Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy
NA, Bergsma DJ, Yanagisawa M (1998) Orexins and orexin
receptors: a family of hypothalamic neuropeptides and G
protein-coupled receptors that regulate feeding behavior. Cell
92:573-585.
23. Marcus JN, Aschkenasi CJ, Lee CE, Chemelli RM, Saper
CB,
Yanagisawa M, Elmquist JK (2001) Differential expression
of orexin receptors 1 and 2 in the rat brain. J Comp Neurol
435:6-25.
24. Bourgin P, Huitrón-Résendiz S, Spier AD, Fabre V, Morte
B, Criado JR, Sutcliffe JG, Henriksen SJ, de Lecea L (2000)
Hypocretin-1 modulates rapid eye movement sleep through
activation of locus coeruleus neurons. J Neurosci 20:7760-
7765.
25. Lu J, Bjorkum AA, Xu M, Gaus SE, Shiromani PJ, Saper CB
(2002) Selective activation of the extended ventrolateral
preoptic nucleus during rapid eye movement sleep. J Neurosci
22:4568-4576.

26. Ko EM, Estabrooke IV, McCarthy M, Scammell TE (2003)
Wake-related activity of tuberomammillary neurons in rats.
Brain Res 992:220-226.
27. Gallopin T, Luppi PH, Cauli B, Urade Y, Rossier J,
Hayaishi
O, Lambolez B, Fort P (2005) The endogenous somnogen
adenosine excites a subset of sleep-promoting neurons via
A2A receptors in the ventrolateral preoptic nucleus. Neuro-
science 134:1377-1390.
28. Sherin JE, Shiromani PJ, McCarley RW, Saper CB (1996)
Activation of ventrolateral preoptic neurons during sleep.
Science 271:216-219.
29. Basheer R, Strecker RE, Thakkar MM, McCarley RW (2004)
Adenosine and sleep-wake regulation. Prog Neurobiol
73:379-396.
30. Obal F Jr, Krueger JM (2003) Biochemical regulation of
non-
rapid-eye-movement sleep. Front Biosci 8:d520-d550.
31. Franken P, Dijk DJ, Tobler I, Borbély AA (1991) Sleep
depri-
vation in rats: effects on EEG power spectra, vigilance states,
and cortical temperature. Am J Physiol 261:R198-R208.
32. Webb WB, Agnew HW Jr (1971) Stage 4 sleep: influence of
time course variables. Science 174:1354-1356.
33. Borbély AA, Baumann F, Brandeis D, Strauch I, Lehmann
D (1981) Sleep deprivation: effect on sleep stages and EEG
power density in man. Electroencephalogr Clin Neurophysiol

41
51:483-495.
34. Beersma DG, Daan S, Dijk DJ (1987) Sleep intensity and
timing: a model for their circadian control. Lect Math Life Sci
19:39-62.
35. Akerstedt T, Gillberg M (1986) Sleep duration and the
power spectral density of the EEG. Electroencephalogr Clin
Neurophysiol 64:119-122.
36. Dijk DJ, Brunner DP, Borbély AA (1991) EEG power
density
during recovery sleep in the morning. Electroencephalogr
Clin Neurophysiol 78:203-214.
37. Majde JA, Krueger JM (2005) Links between the innate
immune system and sleep. J Allergy Clin Immunol 116:1188-
1198.
38. Yoshida H, Peterfi Z, García-García F, Kirkpatrick R,
Yasuda
T, Krueger JM (2004) State-specific asymmetries in EEG slow
wave activity induced by local application of TNFα. Brain Res
1009:129-136.
39. Luk WP, Zhang Y, White TD, Lue FA, Wu C, Jiang CG,
Zhang
L, Moldofsky H (1999) Adenosine: a mediator of interleukin-
1beta-induced hippocampal synaptic inhibition. J Neurosci
19:4238-4244.

40. Brandt JA, Churchill L, Rehman A, Ellis G, Mémet S, Israël
A,
Krueger JM (2004) Sleep deprivation increases the activation
of nuclear factor kappa B in lateral hypothalamic cells. Brain
Res 1004:91-97.
41. Moore RY, Eichler VB (1972) Loss of a circadian adrenal
corticosterone rhythm following suprachiasmatic lesions in
the rat. Brain Res 42:201-206.
42. C a s s on e V M , C h e s wor t h M J, A r m s t rong SM
( 1 9 8 6 )
Entrainment of rat circadian rhythms by daily injection of
melatonin depends upon the hypothalamic suprachiasmatic
nuclei. Physiol Behav 36:1111-1121.
43. Deurveilher S, Semba K (2005) Indirect projections from
the suprachiasmatic nucleus to major arousal-promoting
cell groups in rat: implications for the circadian control of
behavioural state. Neuroscience 130:165-183.
44. Saper CB, Lu J, Chou TC, Gooley J (2005) The
hypothalamic
integrator for circadian rhythms. Trends Neurosci 28:152-
157.
45. L e w y AJ, Cut ler NL, Sack RL (1999) The endogenous
melatonin profile as a marker for circadian phase position. J
Biol Rhythms 14:227-236.
46. Buijs RM, Wortel J, Van Heerikhuize JJ, Feenstra MG, Ter
Horst GJ, Romijn HJ, Kalsbeek A (1999) Anatomical and
functional demonstration of a multisynaptic suprachiasmatic
nucleus adrenal (cortex) pathway. Eur J Neurosci 11:1535-
1544.

47. Hefez A, Metz L, Lavie P (1987) Long-term effects of
extreme
situational stress on sleep and dreaming. Am J Psychiatry
144:344-347.
48. Cartwright RD, Wood E (1991) Adjustment disorders of
sleep: the sleep effects of a major stressful event and its
resolution. Psychiatry Res 39:199-209.
49. Kageyama T, Nishikido N, Kobayashi T, Kurokawa Y,
Kaneko
T, Kabuto M (1998) Self-reported sleep quality, job stress, and
daytime autonomic activities assessed in terms of short-term
heart rate variability among male white-collar workers. Ind
Health 36:263-272.
50. Hall M, Buysse DJ, Nowell PD, Nofzinger EA, Houck P,
Reynolds CF 3rd, Kupfer DJ (2000) Symptoms of stress
and depression as correlates of sleep in primary insomnia.
Psychosom Med 62:227-230.
51. Verlander LA, Benedict JO, Hanson DP (1999) Stress and
sleep patterns of college students. Percept Mot Skills 88:893-
898.
52. Paulsen VM, Shaver JL (1991) Stress, support,
psychological
states and sleep. Soc Sci Med 32:1237-1243.
53. Cernovsky ZZ (1984) Life stress measures and reported
frequency of sleep disorders. Percept Mot Skills 58:39-49.
54. Reynolds CF 3rd, Hoch CC, Buysse DJ, Houck PR, Schler-
nitzauer M, Pasternak RE, Frank E, Mazumdar S, Kupfer DJ
(1993) Sleep after spousal bereavement: a study of recovery

from stress. Biol Psychiatry 34:791-797.
55. Weinberger M, Hiner SL, Tierney WM (1987) In support of
hassles as a measure of stress in predicting health outcomes. J
Behav Med 10:19-31.
56. Hicks R A, G arci a ER (1987) L e vel of stress and sleep
duration. Percept Mot Skills 64:44-46.
57. Bastien CH, Vallières A, Morin CM (2004) Precipitating
factors of insomnia. Behav Sleep Med 2:50-62.
58. Linton SJ (2004) Does work stress predict insomnia? A
prospective study. Br J Health Psychol 9:127-136.
59. Morin CM, Rodrigue S, Ivers H (2003) Role of stress,
arousal,
and coping skills in primary insomnia. Psychosom Med
65:259-267.
60. Dunn AJ, Berridge CW (1990) Physiological and behavioral
responses to corticotropin-releasing factor administration:
is CRF a mediator of anxiety or stress responses? Brain Res
Brain Res Rev 15:71-100.
61. Chrousos GP, Gold PW (1992) The concepts of stress and
stress system disorders. Overview of physical and behavioral
homeostasis. JAMA 267:1244-1252.
62. McEwen BS, Sapolsky RM (1995) Stress and cognitive
function. Curr Opin Neurobiol 5:205-216.
http://dx.doi.org/10.5607/en.2012.21.4.141

63. Rock JP, Oldfield EH, Schulte HM, Gold PW, Kornblith PL,
Loriaux L, Chrousos GP (1984) Corticotropin releasing
factor administered into the ventricular CSF stimulates the
pituitary-adrenal axis. Brain Res 323:365-368.
64. Bierhaus A, Wolf J, Andrassy M, Rohleder N, Humpert
PM, Petrov D, Ferstl R, von Eynatten M, Wendt T, Rudofsky
G, Joswig M, Morcos M, S chwaninger M, McEwen B,
Kirschbaum C, Nawroth PP (2003) A mechanism converting
psychosocial stress into mononuclear cell activation. Proc
Natl Acad Sci U S A 100:1920-1925.
65. Kato T, Montplaisir JY, Lavigne GJ (2004) Experimentally
induced arousals during sleep: a cross-modality matching
paradigm. J Sleep Res 13:229-238.
66. Born J, Fehm HL (1998) Hypothalamus-pituitary-adrenal
activity during human sleep: a coordinating role for the
limbic hippocampal system. Exp Clin Endocrinol Diabetes
106:153-163.
67. Steiger A, Guldner J, Knisatschek H, Rothe B, Lauer C,
Hols-
boer F (1991) Effects of an ACTH/MSH(4-9) analog (HOE
427) on the sleep EEG and nocturnal hormonal secretion in
humans. Peptides 12:1007-1010.
68. Meerlo P, Pragt BJ, Daan S (1997) Social stress induces
high
intensity sleep in rats. Neurosci Lett 225:41-44.
69. Marinesco S, B onnet C, C espuglio R (1999) Influence
o f s t re s s du r at i o n o n t h e s l e e p re b o u n d i n

du c e d b y
immobilization in the rat: a possible role for corticosterone.
Neuroscience 92:921-933.
70. Benschop RJ, Godaert GL, Geenen R, Brosschot JF, De
Smet
MB, Olff M, Heijnen CJ, Ballieux RE (1995) Relationships
between cardiovascular and immunological changes in an
experimental stress model. Psychol Med 25:323-327.
71. Kiecolt-Glaser JK, Glaser R (1995)
Psychoneuroimmunology
and health consequences: data and shared mechanisms.
Psychosom Med 57:269-274.
72. Irwin M, Smith TL, Gillin JC (1992)
Electroencephalographic
sleep and natural killer activity in depressed patients and
control subjects. Psychosom Med 54:10-21.
73. Axelsson J, Ingre M, Akerstedt T, Holmbäck U (2005)
Effects
of acutely displaced sleep on testosterone. J Clin Endocrinol
Metab 90:4530-4535.
74. Braun AR , B alkin TJ, Wesenten NJ, C arson RE, Varga
M, Baldwin P, Selbie S, Belenky G, Herscovitch P (1997)
Regional cerebral blood flow throughout the sleep-wake
cycle. An H2(15)O PET study. Brain 120:1173-1197.
75. Renko AK, Hiltunen L, Laakso M, R ajala U, Keinänen-
Kiukaanniemi S (2005) The relationship of glucose tolerance
to sleep disorders and daytime sleepiness. Diabetes Res Clin
Pract 67:84-91.
76. Vgontzas AN, Zoumakis E, Lin HM, Bixler EO, Trakada

G, Chrousos GP (2004) Marked decrease in sleepiness in
patients with sleep apnea by etanercept, a tumor necrosis
factor-alpha antagonist. J Clin Endocrinol Metab 89:4409-
4413.
77. Spiegel K, Tasali E, Penev P, Van Cauter E (2004) Brief
communication: sleep curtailment in healthy young men is
associated with decreased leptin levels, elevated ghrelin levels,
and increased hunger and appetite. Ann Intern Med 141:846-
850.
78. Bonnet MH, Arand DL (1995) 24-Hour metabolic rate in
insomniacs and matched normal sleepers. Sleep 18:581-588.
79. Lamarche CH, Ogilvie RD (1997) Electrophysiological
changes during the sleep onset period of psychophysiological
insomniacs, psychiatric insomniacs, and normal sleepers.
Sleep 20:724-733.
80. Nofzinger EA, Buysse DJ, Germain A, Price JC, Miewald
JM, Kupfer DJ (2004) Functional neuroimaging evidence for
hyperarousal in insomnia. Am J Psychiatry 161:2126-2128.
81. Spielman AJ, Caruso LS, Glovinsky PB (1987) A behavioral
perspective on insomnia treatment. Psychiatr Clin North Am
10:541-553.
82. Morin CM (1993) A cognitive-behavioral conceptualization
of insomnia. In: Insomnia: psychological assessment and
management (Morin CM, ed), pp 46-60. Guilford Press, New
York.
83. Harvey AG (2002) A cognitive model of insomnia. Behav
Res
Ther 40:869-893.

84. E spi e C A ( 2 0 0 2 ) In s om n i a : c onc e ptu a l i s
su e s i n t he
development, persistence, and treatment of sleep disorder in
adults. Annu Rev Psychol 53:215-243.
85. Edinger JD, Fins AI, Glenn DM, Sullivan RJ Jr, Bastian LA,
Marsh GR, Dailey D, Hope TV, Young M, Shaw E, Vasilas
D (2000) Insomnia and the eye of the beholder: are there
clinical markers of objective sleep disturbances among adults
with and without insomnia complaints? J Consult Clin
Psychol 68:586-593.
86. Perlis ML, Giles DE, Mendelson WB, Bootzin RR, Wyatt JK
(1997) Psychophysiological insomnia: the behavioural model
and a neurocognitive perspective. J Sleep Res 6:179-188.
87. Han KS (2007) Stress of the mid-life stage. Korean J Stress
Res
15:263-270.
88. Seaward BL (2009) Managing stress: principles and
strategies
for health and well-being, 6th ed. Jones and Bartlett Publi-
shers, Sudbury, MA.
C
Gender differences in sleep diso
rders
Vidya Krishnan and Nancy A. Collop
Purpose of review

To evaluate recent evidence regarding gender differences
in sleep.
Recent findings
Women have better sleep quality compared with men, with
longer sleep times, shorter sleep-onset latency and higher
sleep efficiency. Despite this, women have more sleep-
related complaints than men. The amount of slow-wave
sleep decreases with age in men and women. Normal
physiologic periods, including puberty, menstruation,
pregnancy, and menopause, are associated with alterations
in sleep patterns.
Gender differences in normal sleep may underlie the
observed differences in risk of sleep disorders. Studies of
insomnia support a female predominance, with increased
divergence of prevalence between men and women with
older age. Recent findings for the gender differences in
obstructive sleep apnea have focused on differences in
local neuromuscular reflexes and central ventilatory control.

Restless legs syndrome has a slight female predominance,
whereas rapid eye movement sleep behavior disorder and
Kleine –Levin syndrome are more common in men.
Summary
Gender differences in sleep become apparent after the
onset of puberty. Menstrual cycles, pregnancy, and
menopause can alter sleep architecture. Gender-related
differences in sleep disorders, such as obstructive sleep
apnea, insomnia, and restless legs syndrome, include
differences in prevalence, pathophysiology, clinical
presentation, and response to therapy.
Keywords
gender, sleep, sleep disorders
Curr Opin Pulm Med 12:383 – 389. � 2006 Lippincott Williams
& Wilkins.
Division of Pulmonary and Critical Care, Department of
Medicine, Johns Hopkins
University, Baltimore Maryland, USA
Correspondence to Dr Nancy A. Collop, MD, 1830 E.
Monument St., Rm 555,
Baltimore, MD 21205, USA

Tel: +1 410 502 7039; fax: +1 410 955 0036; e-mail:
[email protected]
Current Opinion in Pulmonary Medicine 2006, 12:383 – 389
Abbreviations
NREM n
opyr
onrapid eye movement
OSA o
bstructive sleep apnea
REM ra
pid eye movement
RLS re
stless legs syndrome
SWS s
low wave sleep
� 2006 Lippincott Williams & Wilkins
1070-5287
ight © Lippincott Williams & Wilkins. Unauth
Introduction
Sleep occupies one-third of our lifetime, and plays a
major role in maintaining health. Gender-related

differences in normal sleep may underlie the risk of
developing sleep disorders. Previous reviews have
been published on the topic of gender differences in
sleep [1]. Our objective was to evaluate the recent
evidence regarding gender differences in sleep and
sleep disorders.
Gender differences in normal sleep
In order to understand the gender differences in sleep
disorders, we must first address gender differences in
‘normal sleep’. These include the stimulus for sleep
onset, the duration of sleep, and sleep architecture.
What is ‘normal sleep’?
Sleep is the ‘reversible behavioral state of perceptual
disengagement from and unresponsiveness to the
environment’ [2]. Sleep is a heterogeneous state that
includes rapid eye movement (REM) and nonrapid
eye movement (NREM) sleep. REM is characterized
by mixed-frequency electroencephalogram activity,
muscle atonia, and eye movements, whereas NREM

sleep is characterized by quiescent electroencephalogram
synchrony with muscle activation potential. NREM sleep
is further classified by depth of sleep, from Stage 1 to
Stage 3 – 4 [slow wave sleep (SWS)].
The determinants of sleep onset are multifactorial, and
include duration of prior wakefulness, time of day,
genetics, environment, comorbid conditions and medi-
cation effects. The timing, duration and architecture of
sleep changes in humans with age, as shown in Table 1.
With older age, frequent arousals and advanced sleep
phase contribute to decreased sleep efficiency, indepen-
dent of the presence of sleep disorders.
Men and women sleep differently
Most research in gender differences in sleep has been
conducted in adults. Among young adults, women have
better sleep quality (shorter sleep onset latency, higher
sleep efficiency) compared with men [3]. While healthy
women appear to objectively have better quality sleep

than men, women of all adult age groups report more sleep
problems, including inadequate sleep time and insomnia
[4,5
�
]. Additionally, men are more likely than women to
function at their best during the day with less than seven
hours of sleep (58% versus 43%) [6
��
]. This suggests that
women are either more susceptible to clinical symptoms
orized reproduction of this article is prohibited.
383
mailto:[email protected]
C
384 Sleep and respiratory neurobiology
Table 1 Normal sleep characteristics in humans across the age
spectrum
Age group Sleep onset Sleep duration Sleep architecture Sleep
cycling
Newborns Via REM (‘active’) sleep 16 h – nonconsecutive.
Usually four to five sleep

periods per 24 h
‘Active’ and ‘quiet’ sleep represent
immature forms of REM and
NREM sleep
50– 60 min
Childhood Transitions from REM to
NREM sleep
Circadian rhythm of sleep –
majority of sleep during
nocturnal hours. Single
consolidated sleep period
usually by age 5 years
Fully developed REM and NREM
architecture achieved by age 6 months
60– 90 min
Maximal amount of SWS
Young adults Via NREM sleep 7 –8 h Stage 1 NREM sleep : 2 –
5% 90– 110 min
Stage 2 NREM sleep : 45 –55% SWS predominates in
first one-third of night
Stage 3 NREM sleep : 3 –8% REM predominates in
last one-third of night
Stage 4 NREM sleep : 10 –15%
REM : 20– 25%
Older adults Via NREM sleep Increased interindividual

variability
Reduction in SWS. Increased number
of arousals, decreased sleep efficiency
90– 110 min
REM predominates in
last one-third of night
REM, rapid eye movement; NREM, nonrapid eye movement;
SWS, slow wave sleep (Stages 3 and 4).
from inadequate sleep, or are more likely to report symp-
toms in general.
Subjective and objective sleep quality decline with age.
REM sleep appears to be well preserved with age, while
the amount of SWS declines. By visual staging methods,
women appear to have less of a decline in SWS than
men [7 – 9]. The use of electroencephalogram spectral
analysis for sleep staging, however, does not support
this gender difference in the amount of SWS [10,11].
Older women do have a higher rate of sleep complaints
compared with age-matched men [12], but the reasons
for this observed difference has not been elucidated

to date.
Conditions that impact sleep
Gender differences in sleep and sleep disorders are
exacerbated by distinct hormonal and physical changes
in women that confer altered risk for sleep disturbances
and sleep disorders.
Puberty
In prepubertal children, differences in sleep quality and
sleep duration by gender have not been consistently
shown. After puberty, hormonal fluctuations, environ-
mental stresses (e.g. early school time), and onset of
affective disorders (e.g. depression, anxiety) contribute
to changes in sleep. Knutson [13] studied the association
between sleep and pubertal development in cohort of
adolescents aged 12 – 16 years. The author reported
increased sleep problems (insomnia, daytime tiredness,
and insufficient sleep) associated with pubertal develop-
ment in girls, but not in boys [13]. The author did not find
an association between height velocity (inches/year) and

sleep duration in boys or girls in this study, suggesting
that the hormonal changes, rather than the physical
opyright © Lippincott Williams & Wilkins. Unautho
changes, associated with puberty may explain the
changes in sleep.
Menstrual cycle
The menstrual cycle of young healthy women is charac-
terized by fluctuations of hormone levels (e.g. gonadal
steroids, pituitary hormones, melatonin, and cortisol) and
temperature control. Clinical studies to examine the effect
of the menstrual cycle phase on sleep have been limited
by: small numbers of participants; high variance in the
length of menstrual cycles within and between women; a
lack of control for ovulatory timing, particularly in peri-
menopausal women and women with anovulatory cycles;
differences in sleep at home (e.g. young children may
interrupt sleep) versus in the sleep laboratory; time restric-
tions limiting the number of menstrual phases studied; and
a lack of control for comorbid affective disorders that may

affect sleep quality [14]. Nonetheless, there are data to
suggest differences in objective sleep and subjective
symptoms across the menstrual cycle. Survey studies have
supported the finding that the luteal phase is associated
with more sleep disruption, such as longer initial sleep
latency, lower sleep efficiency, and poorer subjective sleep
quality, compared with the follicular phase [15,16]. Other
studies using overnight polysomnography, however, have
failed to show objective differences in sleep architecture
by menstrual phase [17,18].
The International Classification of Sleep Disorders
(2nd edition) [19
��
] includes a diagnostic category for
menstrual-related hypersomnia, which is described as
recurrent 1-week episodes of hypersomnia that occur in
association with the menstrual cycle, and usually resolves
rapidly at the time of menses. Onset of this disorder

generally occurs within a few months of menarche, and
oral contraceptives are effective treatment.
rized reproduction of this article is prohibited.
C
Gender differences in sleep disorders Krishnan and Collop 385
Pregnancy
A review of the effects of pregnancy on respiration and
sleep was recently published [20]. The physical changes
of pregnancy, including abdominal distension, fetal
movement, bladder distention, urinary frequency, back-
ache and heartburn, may all result in reduced sleep
efficiency and increased nocturnal awakenings. Insomnia
and daytime sleepiness are common complaints during
pregnancy. Polysomnography reveals reduced slow wave
and REM stages of sleep, and increased total sleep time
and wake after sleep onset, all of which progress during
the course of the pregnancy. Sleep efficiency is also
reduced, and remains poor up to 3 months post partum

[21,22].
Hormonal changes with pregnancy, especially increased
estrogen and progesterone, also affect sleep. Progester-
one can stimulate the ventilatory drive, as well as have a
strong sedating effect. Estrogen is related to changes of
the upper airway, including mucosal edema, hyperemia,
and mucus hypersecretion, all of which can increase
upper airway resistance. Snoring is common during preg-
nancy, occurring in more than 14% of pregnant women by
the third trimester, as compared with 4% of nonpregnant,
age-matched controls [23]. Obstructive sleep apnea
(OSA) has been described during pregnancy and is
associated with pregnancy-induced hypertension and
intrauterine growth retardation [24].
Restless legs syndrome (RLS) can contribute to sleep-
onset insomnia, and can be associated with periodic limb
movements, disrupting nocturnal sleep significantly. In
one large study from Japan [25], the prevalence of RLS in

pregnant women (who did not have RLS before preg-
nancy) ranged from 15% in the first trimester to 23% by
the final trimester. This increased prevalence of RLS
may reflect relative iron or folate deficiency during preg-
nancy [26].
Menopause
Menopause, the cessation of menstrual periods, is associ-
ated with a change in the hormonal environment in
women. The perimenopausal period is associated with
large fluctuations in hormone levels, with a decrease in
circulating estradiol, inhibin, and testosterone, and an
increase in follicular stimulating hormone and luteinizing
hormone. These changes in hormones are associated with
physical, physiologic, and psychologic changes that affect
sleep.
The prevalence of insomnia increases following meno-
pause, from 33 – 36% in premenopausal women to
44 – 61% postmenopause [14]. Reasons for this increase

in insomnia include hot flashes, mood disturbances
(e.g. depression and anxiety), and increase in primary
sleep disorders (e.g. OSA and RLS) with age. Despite
opyright © Lippincott Williams & Wilkins. Unauth
these symptoms, objective evidence of sleep from a large
population-based polysomnographic study shows better
sleep (longer total sleep times, increased SWS, and
increased sleep efficiency) in postmenopausal compared
with premenopausal women [27]. This points to a dis-
connection between subjective and objective qualities of
sleep measured by polysomnography in older women.
Hormone replacement therapy may alleviate some of the
sleep disturbances associated with menopause. Among
postmenopausal women, the prevalence of obstructive
sleep apnea in hormone replacement therapy users is
approximately one-half that of nonusers [28]. Oral syn-
thetic estrogens have been shown to objectively improve
polysomnographic sleep parameters, whereas other stu-
dies of transdermal estrogen, oral conjugated estrogen

with progestin and progesterones [29 – 31] show subjec-
tive sleep improvement without objective changes. Hor-
mone replacement therapy is also highly effective in
treating hot flashes and the accompanying discomfort
[14].
Gender differences in sleep disorders
Gender differences have been observed in many sleep
disorders, including insomnia, OSA, RLS, and others.
Underlying reasons for gender differences in sleep dis-
orders are attributed to differences in normal sleep,
differences in clinical manifestations of disturbances of
sleep, and differences in risk factors for sleep disorders.
Insomnia
Insomnia is the most common sleep complaint, with a
lifetime prevalence of one-third of the general adult
population. Johnson et al. [32] studied 1014 adolescents
from a random sample of an urban health maintenance
organization population, and found no difference in risk
of insomnia in prepubertal girls compared with boys –

but the onset of menses in girls conferred a 2.75-fold
increased risk of insomnia. A recent meta-analysis found a
higher risk of insomnia in women compared with men
(risk ratio, 1.41; 95% confidence interval, 1.28 – 1.55) [5
�
].
In addition, this study suggested an increasingly diver-
gent risk of insomnia in women compared with men with
increasing age, with women over the age of 65 years
having the highest risk of insomnia (risk ratio, 1.73;
95% confidence interval, 1.65 – 1.83).
The relationship between gender and insomnia may be
related to the risk factors for insomnia. Anxiety and
depression are affective disorders that are more common
in women than men, and are associated with insomnia
[33]. Whether the association between insomnia and
depression is cause or effect is still in question – insomnia
is used as a diagnostic criteria for affective disorders, but
insomnia has also been shown to predate and predict a

depressive episode [34]. Insomnia is also more common
C
in persons who are widowed, divorced, or separated, an
association that is stronger in women than men [35].
Additionally, women are more likely to present with
symptoms of insomnia for alternate primary sleep dis-
orders, such as OSA, which contributes to misdiagnoses
and delays in effective treatment.
Women are more likely to present to their physician with
complaints related to sleep, and as a result are more likely
to be prescribed hypnotics, such as benzodiazepines,
sedating antidepressants, and antipsychotics, for the
treatment of insomnia [36,37], despite a lack of evidence
for efficacy and their side-effect profiles. Alcohol is
more commonly used in men than women to self-treat
insomnia [38], which is more likely to cause increases in

subsequent daytime sleepiness.
Obstructive sleep apnea
OSA, defined as an apnea hypopnea index of at least five
events per hour, is prevalent in 24% of men and 9% of
women in the US adult population [39]. The inclusion of
the diagnostic criteria of daytime hypersomnolence
reduces the difference in prevalence between men and
women (4% and 2%, respectively). Differences in the
prevalence of OSA are attributed to differences in clinical
presentation and differences in pathophysiology. A
recent review of the current literature regarding gender
differences in OSA has been published [40,41].
Clinical presentation of OSA
Typical symptoms associated with OSA include snoring,
daytime sleepiness, and witnessed apneic events. Men
usually present with typical symptoms of snoring or
daytime sleepiness. Women, however, are more likely
to present with atypical initial symptoms of insomnia or

fatigue, or have concomitant clinical depression or
hypothyroidism [42], all of which can cause diversion
from the diagnosis of OSA. Witnessed apneic events are
also less commonly reported for women than men.
The difference in the prevalence of OSA by gender is
magnified in the clinic and hospital patient population.
Reasons for this magnified difference include: atypical
presentation of women with OSA making diagnosis and
management of the sleep disorder less likely; the differ-
ence in prevalence of OSA by gender may be increased
with higher severity of disease [43,44]; and women are
less likely to come to the clinic accompanied by their
bedpartner, whose complementary sleep history (of noc-
turnal snoring, witnessed apneas) may assist in the diag-
nosis of OSA.
Pathophysiology of OSA
The upper airway composition, including the soft
palate and tongue volume [45] and pharyngeal length

[46], has been shown to be larger in men than women.
Nonetheless, the upper airway caliber is greater in men
than in women in both normal [47] and OSA [48] patients
during wakefulness, suggesting that characteristics other
than upper airway anatomy are responsible for the pre-
disposition to OSA. Obesity has been identified as a
strong risk factor for OSA. Women are more likely to
be obese (body mass index �30 kg/m2) than men [49].
The distribution of total body fat, however, is probably
more important than the overall body mass index. In men
and women of similar body mass index and waist circum-
ference, men have greater upper body obesity, as
measured by smaller hip circumferences and greater
subscapular skin fold thickness [50], which increases
the resistive load of the upper airway.
Physiologic responses to upper airway collapse include
local neuromuscular reflex activation and central venti-
latory control. There is no conclusive evidence of gender
differences in upper airway neuromuscular responses to

inspiratory flow limitation or predisposition to local
trauma caused by repetitive upper airway collapse. Cen-
tral ventilatory control, however, does have gender differ-
ences. During sleep, women have a lower apnea
threshold (level of arterial carbon dioxide below that at
which an apnea is induced) compared with men [51].
Arousal from sleep induces greater ventilatory instability
in men compared with women [52]. With inspiratory flow
limitation during NREM sleep, women are also less
likely to exhibit apneas [53] and hypoventilation [54]
compared with men. The differences in responses to
physical and chemical changes associated with OSA
may therefore underlie the gender differences in preva-
lence and clinical presentation of the disorder.
Treatment of OSA
Conventional treatment of OSA [55 – 57] is via nasal
continuous positive airway pressure. While nasal continu-
ous positive airway pressure is effective in resolving

upper airway obstruction, compliance to therapy is vari-
able – from 46% to 89% depending on the definition of
compliance. Gender differences in nasal continuous
positive airway pressure compliance are not conclusive,
with some studies showing higher compliance in men and
others showing higher compliance in women.
Other modes of OSA therapy include weight loss, upper
airway surgery, and oral appliances. While women with
OSA have been shown to be generally more obese than
their male counterparts, weight loss in patients with OSA
has been shown to be a more effective treatment strategy
in men compared with women [58]. Bariatric surgery has
been shown to effectively decrease the apnea– hypopnea
index. Men, however, are reported to have a higher risk of
postoperative mortality than women [59], and therefore are
generally not considered good candidates for this pro-
cedure. Upper airway surgeries have not been found to

C
be effective treatment options for OSA, and there is no
evidence to suggest a difference in the results of this
procedure by gender. Oral appliances relieve upper
airway obstruction by mandibular advancement or
tongue protrusion, both of which can potentially increase
the posterior pharyngeal space. Oral appliances are most
beneficial in mild to moderate OSA, which is more com-
mon in men, and in those with supine position-dependent
OSA, which is again more common in men [60,61].
Restless legs syndrome
RLS is a sensory disorder that affects 10% of US adults
[62
�
]. Prevalence studies of RLS indicate a slight female
predominance for the disease [63,64]. This observation
may be accurate and may result from gender differences
in risk factors for developing RLS (e.g. iron deficiency,

psychiatric disorders, medications for psychiatric dis-
orders) or from selection biases inherent in prevalence
studies. Studies of inheritance patterns of RLS are con-
flicted, showing either a higher female-to-female trans-
mission predilection or no gender differentiation.
Prevalence studies for RLS may suggest a higher preva-
lence in women because the sleep disturbance caused by
Table 2 International classification of sleep disorders and
gender
Insomnia
Sleep-related
breathing
disorders Hypersomnia
Female predominant
Adjustment insomnia Menstrual-related
hypersomnia
Psychophysiologic
insomnia
Idiopathic insomnia
Insomnia due to

mental disorder
Male predominant
Central sleep
apnea syndromes
Narcolepsy
Obstructive sleep
apnea syndromes
Kleine–Levin
syndrome
Idiopathic
hypoventilation
No gender predominance
Inadequate sleep
hygiene
Congenital
central alveolar
hypoventilation
Idiopathic
hypersomnia
Behavioral insomnia
of childhood
Insufficient sleep
syndrome
a Violent or injury associated with sleepwalking is more

common in men.
b Sleep enuresis is more common in boys than girls; in older
adults, sleep
RLS may have more of an impact on women than men. As
mentioned earlier, women are more prone to insomnia
than men, and RLS may simply exacerbate this tendency
for sleep disruption in women. Evidence that women
have a lower threshold for pain [65] and will report
increased distress of clinical pain [66] also suggests that
women are more likely to present to their physician or
participate in a research study to alleviate their symptoms
of RLS.
Other sleep disorders
Sleep disorders of lesser prevalence have also been
studied for gender differences. REM sleep behavior
disorder is a parasomnia characterized by complex motor
activity during REM sleep. While the overall prevalence
of REM sleep behavior disorder is unknown, this disorder
affects primarily men older than 50 years [67]. Narcolepsy
is a sleep disorder that manifests with symptoms of

excessive daytime sleepiness, cataplexy, hypnogogic hal-
lucinations, and/or sleep paralysis, and has a slight male
predominance [19
��
]. Kleine – Levin syndrome is a rare
disorder of symptoms that include hypersomnia, hyper-
phagia, and hypersexuality. Arnulf et al. [68] reported a
meta-analysis of all Kleine – Levin syndrome reports in
predominance
Circadian rhythm
sleep disorders Parasomnias
Sleep-related
movement
disorders
Nightmares Restless legs
syndrome
Sleep-related
dissociative
disorders
Exploding head
syndrome
Sleep-related
hallucinations

Sleep-related
eating disorders
Confusional arousals Periodic limb
movement
disorder
Rapid eye movement
sleep behavior
disorders
Sleep-related leg
cramps
Sleep terrors
Sleep paralysis
Delayed sleep
phase
Sleepwalkinga Sleep-related
rhythmic
movement
disorder
Advance sleep
phase
Sleep enuresisb Sleep-related
bruxism
Irregular
sleep-wake

Sleep-related groaning
Free-running
enuresis is more common in women than men.
C
the literature. They found a mean age onset of 15 years,
with overall prevalence higher in males (68%) but a
longer duration of disease in women (9 � 8.7 versus
5.4 � 5.6 years, P ¼ 0.01).
Numerous other sleep disorders have been identified with
potential gender differences in prevalence, symptoms, or
predisposition. These are summarized in Table 2.
Conclusion
Gender differences in sleep quality and sleep efficiency
have been established in healthy individuals. These
differences are magnified in the presence of sleep dis-
orders, such as insomnia and OSA, which further disrupt
nocturnal sleep and subsequent daytime functioning.
While gender differences in hormone milieu, body fat

composition, and physical attributes contribute to differ-
ences in sleep disorder diagnosis and manifestation, it
would clearly be an oversimplification to conclude that
these are the only differences between men and women.
References and recommended reading
Papers of particular interest, published within the annual period
of review, have
been highlighted as:
� of special interest
�� of outstanding interest
Additional references related to this topic can also be found in
the Current
World Literature section in this issue (p. 467).
1 Collop NA, Adkins D, Phillips BA. Gender differences in
sleep and sleep-
disordered breathing. Clin Chest Med 2004; 25:257 – 268.
2 Carskadon MA, Dement WC. Normal human sleep: an
overview. In: Kryger
MH, Roth T, Dement WC, editors. Principles and practice of
sleep medicine.
Philadelphia, PA: Elsevier Saunders; 2005. p. 13.
3 Goel N, Kim H, Lao RP. Gender differences in
polysomnographic sleep in
young healthy sleepers. Chronobiol Int 2005; 22:905 – 915.
4 Bixler EO, Vgontzas AN, Lin HM, et al. Insomnia in central
Pennsylvania.
J Psychosom Res 2002; 53:589 – 592.

5
�
Zhang B, Wing YK. Sex differences in insomnia: a meta-
analysis. Sleep 2006;
29:85 – 93.
A recent meta-analysis of the literature on insomnia and gender
differences.
6
��
National Sleep Foundation. 2005 sleep in America poll.
http://www.
sleepfoundation.org/_content/hottopics/2005_summary_of_findi
ngs.pdf.
[Accessed 31 May 2006]
The National Sleep Foundation’s report of results of a
nationally representative
survey of sleep habits of adults in the United States in 2005.
7 Hume KI, Van F, Watson A. A field study of age and gender
differences in
habitual adult sleep. J Sleep Res 1998; 7:85 – 94.
8 Ehlers CL, Kupfer DJ. Slow-wave sleep: do young adult men
and women age
differently? J Sleep Res 1997; 6:211 – 215.
9 Reynolds CF III, Monk TH, Hoch CC, et al.
Electroencephalographic sleep in
the healthy ‘old old’: a comparison with the ‘young old’ in
visually scored and

automated measures. J Gerontol 1991; 46:M39 – M46.
10 Voderholzer U, Al Shajlawi A, Weske G, et al. Are there
gender differences in
objective and subjective sleep measures? A study of insomniacs
and healthy
controls. Depress Anxiety 2003; 17:162 – 172.
11 Armitage R, Hoffmann R, Trivedi M, et al. Slow-wave
activity in NREM sleep:
sex and age effects in depressed outpatients and healthy
controls. Psychiatry
Res 2000; 95:201 – 213.
12 Doghramji K. The epidemiology and diagnosis of insomnia.
Am J Manag Care
2006; 12 (8 Suppl):S214 – S220.
13 Knutson KL. The association between pubertal status and
sleep duration
and quality among a nationally representative sample of US
adolescents.
Am J Hum Biol 2005; 17:418 – 424.
14 Moline ML, Broch L, Zak R. Sleep in women across the life
cycle from
adulthood through menopause. Med Clin North Am 2004;
88:705 – 736; ix.
15 Manber R, Bootzin RR. Sleep and the menstrual cycle.
Health Psychol 1997;
16:209– 214.
16 Shaver JL. Women and sleep. Nurs Clin North Am 2002;
37:707 – 718.

17 Ito M, Kohsaka M, Fukuda N, et al. Effects of menstrual
cycle on plasma
melatonin level and sleep characteristics. Jpn J Psychiatry
Neurol 1993;
47:478– 479.
18 Driver HS, Dijk DJ, Werth E, et al. Sleep and the sleep
electroencephalogram
across the menstrual cycle in young healthy women. J Clin
Endocrinol Metab
1996; 81:728 – 735.
19
��
American Academy of Sleep Medicine. International
classification of sleep
disorders: diagnostic and coding manual. 2nd ed. Westchester,
IL: American
Academy of Sleep Medicine; 2005.
American Academy of Sleep Medicine’s updated classification
of sleep disorders.
20 Wise RA, Polito AJ, Krishnan V. Respiratory physiologic
changes in preg-
nancy. Immunol Allergy Clin North Am 2006; 26:1 – 12.
21 Pien GW, Schwab RJ. Sleep disorders during pregnancy.
Sleep 2004;
27:1405 – 1417.
22 Santiago JR, Nolledo MS, Kinzler W, et al. Sleep and sleep
disorders in
pregnancy. Ann Intern Med 2001; 134:396 – 408.

23 Schweiger MS. Sleep disturbance in pregnancy. A subjective
survey. Am J
Obstet Gynecol 1972; 114:879 – 882.
24 Franklin KA, Holmgren PA, Jonsson F, et al. Snoring,
pregnancy-induced
hypertension, and growth retardation of the fetus. Chest 2000;
117:137 –
141.
25 Suzuki K, Ohida T, Sone T, et al. The prevalence of restless
legs syndrome
among pregnant women in Japan and the relationship between
restless legs
syndrome and sleep problems. Sleep 2003; 26:673 – 677.
26 Manconi M, Govoni V, De Vito A, et al. Restless legs
syndrome and
pregnancy. Neurology 2004; 63:1065 – 1069.
27 Young T, Finn L, Austin D, et al. Menopausal status and
sleep-disordered
breathing in the Wisconsin Sleep Cohort Study. Am J Respir
Crit Care Med
2003; 167:1181 – 1185.
28 Shahar E, Redline S, Young T, et al. Hormone replacement
therapy and sleep-
disordered breathing. Am J Respir Crit Care Med 2003;
167:1186 –
1192.
29 Antonijevic IA, Stalla GK, Steiger A. Modulation of the
sleep electroen-
cephalogram by estrogen replacement in postmenopausal
women. Am J

Obstet Gynecol 2000; 182:277 – 282.
30 Purdie DW, Empson JA, Crichton C, et al. Hormone
replacement therapy,
sleep quality and psychological wellbeing. Br J Obstet Gynaecol
1995;
102:735 – 739.
31 Montplaisir J, Lorrain J, Denesle R, et al. Sleep in
menopause: differential effects
of two forms of hormone replacement therapy. Menopause 2001;
8:10–16.
32 Johnson EO, Roth T, Schultz L, et al. Epidemiology of DSM-
IV insomnia in
adolescence: lifetime prevalence, chronicity, and an emergent
gender differ-
ence. Pediatrics 2006; 117:e247 – e256.
33 Kornstein SG. Gender differences in depression: implications
for treatment.
J Clin Psychiatry 1997; 58 (Suppl 15):12 – 18.
34 Ford DE, Kamerow DB. Epidemiologic study of sleep
disturbances and
psychiatric disorders: an opportunity for prevention? JAMA
1989;
262:1479 – 1484.
35 Ohayon M. Epidemiological study on insomnia in the general
population.
Sleep 1996; 19 (3 Suppl):S7 – S15.
36 Walsh JK, Schweitzer PK. Ten-year trends in the
pharmacological treatment of
insomnia. Sleep 1999; 22:371 – 375.

37 Whitney CW, Enright PL, Newman AB, et al. Correlates of
daytime sleepiness
in 4578 elderly persons: the Cardiovascular Health Study. Sleep
1998;
21:27 – 36.
38 Roth T. Prevalence, associated risks, and treatment patterns
of insomnia.
J Clin Psychiatry 2005; 66 (Suppl 9):1 – 13.
39 Young T, Palta M, Dempsey J, et al. The occurrence of
sleep-disordered
breathing among middle-aged adults. N Engl J Med 1993;
328:1230 – 1235.
40 Krishnan V, Collop NA. Gender differences in obstructive
sleep apnea. In:
Kushida CA, editor. Obstructive sleep apnea: clinical issues,
diagnosis, and
treatment. New York: Taylor & Francis Group, LLC; 2006 in
press.
41 Jordan A, Doug McEvoy R. Gender differences in sleep
apnea: epidemiology,
clinical presentation and pathogenic mechanisms. Sleep Med
Rev 2003;
7:377 – 389.
42 Shepertycky MR, Banno K, Kryger MH. Differences between
men and women
in the clinical presentation of patients diagnosed with
obstructive sleep apnea
syndrome. Sleep 2005; 28:309 – 314.

http://www.sleepfoundation.org/_content/hottopics/2005_summ
ary_of_findings.pdf
http://www.sleepfoundation.org/_content/hottopics/2005_summ
ary_of_findings.pdf
C
43 Shahar E, Whitney CW, Redline S, et al. Sleep-disordered
breathing and
cardiovascular disease: cross-sectional results of the Sleep
Heart Health
Study. Am J Respir Crit Care Med 2001; 163:19 – 25.
44 Duran J, Esnaola S, Rubio R, et al. Obstructive sleep apnea-
hypopnea
and related clinical features in a population-based sample of
subjects
aged 30 to 70 yr. Am J Respir Crit Care Med 2001; 163 (3 Pt
1):685 –
689.
45 Whittle AT, Marshall I, Mortimore IL, et al. Neck soft tissue
and fat distribution:
comparison between normal men and women by magnetic
resonance imag-
ing. Thorax 1999; 54:323 – 328.
46 Pillar G, Malhotra A, Fogel R, et al. Airway mechanics and
ventilation in
response to resistive loading during sleep: influence of gender.
Am J Respir
Crit Care Med 2000; 162:1627 – 1632.
47 Brooks LJ, Strohl KP. Size and mechanical properties of the

pharynx
in healthy men and women. Am Rev Respir Dis 1992; 146:1394
–
1397.
48 Mohsenin V. Gender differences in the expression of sleep-
disordered breath-
ing: role of upper airway dimensions. Chest 2001; 120:1442 –
1447.
49 Trinder J, Kay A, Kleiman J, et al. Gender differences in
airway resistance
during sleep. J Appl Physiol 1997; 83:1986 – 1997.
50 Millman RP, Carlisle CC, McGarvey ST, et al. Body fat
distribution and sleep
apnea severity in women. Chest 1995; 107:362 – 366.
51 Zhou XS, Shahabuddin S, Zahn BR, et al. Effect of gender
on the develop-
ment of hypocapnic apnea/hypopnea during NREM sleep. J Appl
Physiol
2000; 89:192 – 199.
52 Jordan AS, Eckert DJ, Catcheside PG, McEvoy RD.
Ventialtory response to
brief arousal from nonrapid eye movement sleep is greater in
men than in
women. Am J Respir Crit Care Med 2003; 168:1512 – 1519.
53 Kirkness JP, Patil S, Schneider H, et al. Women are
protected against
obstructive sleep apnea through reduced upper airway
mechanical loads
and active neuromuscular responses [abstract]. Am J Respir Crit
Care Med

2006, 171.
54 Krishnan V, Pichard L, Patil S, et al. Gender differences in
ventilatory response
to inspiratory flow limitation during non rapid eye movement
(NREM) sleep
[abstract]. Am J Respir Crit Care Med 2006, 171.
55 Hoffstein V, Viner S, Mateika S, et al. Treatment of
obstructive sleep apnea
with nasal continuous positive airway pressure. Patient
compliance, percep-
tion of benefits, and side effects. Am Rev Respir Dis 1992; 145
(4 Pt 1):
841 – 845.
56 Krieger J, Kurtz D, Petiau C, et al. Long-term compliance
with CPAP
therapy in obstructive sleep apnea patients and in snorers. Sleep
1996;
19 (9 Suppl):S136 – S143.
57 Meurice JC, Dore P, Paquereau J, et al. Predictive factors of
long-term
compliance with nasal continuous positive airway pressure
treatment in sleep
apnea syndrome. Chest 1994; 105:429 – 433.
58 Engleman HM, McDonald JP, Graham D, et al. Randomized
crossover trial of
two treatments for sleep apnea/hypopnea syndrome: continuous
positive
airway pressure and mandibular repositioning splint. Am J
Respir Crit Care
Med 2002; 166:855 – 859.

59 Rasheid S, Banasiak M, Gallagher SF, et al. Gastric bypass
is an effective
treatment for obstructive sleep apnea in patients with clinically
significant
obesity. Obes Surg 2003; 13:58 – 61.
60 Marklund M, Stenlund H, Franklin KA. Mandibular
advancement devices in
630 men and women with obstructive sleep apnea and snoring:
tolerability
and predictors of treatment success. Chest 2004; 125:1270 –
1278.
61 O’Connor C, Thornley KS, Hanly PJ. Gender differences in
the polysomno-
graphic features of obstructive sleep apnea. Am J Respir Crit
Care Med 2000;
161:1465 – 1472.
62
�
Restless Legs Syndrome Foundation. All about restless legs
syndrome. http://
www.rls.org/NetCommunity/Page.aspx?&pid=200&srcid=178.
[Accessed
31 May 2006]
Website of the Restless Legs Syndrome Foundation, with up-to-
date information
about this clinical entity.
63 Nichols DA, Allen RP, Grauke JH, et al. Restless legs
syndrome symptoms
in primary care: a prevalence study. Arch Intern Med 2003;
163:2323 –

2329.
64 Hening W, Walters AS, Allen RP, et al. Impact, diagnosis
and treatment
of restless legs syndrome (RLS) in a primary care population:
the REST
(RLS epidemiology, symptoms, and treatment) primary care
study. Sleep Med
2004; 5:237 – 246.
65 Vallerand AH, Polomano RC. The relationship of gender to
pain. Pain Manag
Nurs 2000; 1 (3 Suppl 1):8 – 15.
66 Unruh AM. Gender variations in clinical pain experience.
Pain 1996;
65 (2 – 3):123 – 167.
67 Ferini-Strambi L, Fantini ML, Zucconi M, et al. REM sleep
behavior disorder.
Neurol Sci 2005; 26:s186 – s192.
68 Arnulf I, Zeitzer JM, File J, et al. Kleine – Levin syndrome:
a systematic review of
186 cases in the literature. Brain 2005; 128 (Pt 12):2763 – 2776.
http://www.rls.org/NetCommunity/Page.aspx?amp;pid=200amp;
srcid=178
http://www.rls.org/NetCommunity/Page.aspx?amp;pid=200amp;
srcid=178Gender differences in
sleep™disordersIntroductionGender differences in normal
sleepWhat is ‘normal sleep’?Men and women sleep
differentlyConditions that impact sleepPubertyMenstrual
cyclePregnancyMenopauseGender differences in sleep
disordersInsomniaObstructive sleep apneaClinical presentation

of OSAPathophysiology of OSATreatment of OSARestless legs
syndromeOther sleep disordersConclusionReferences and
recommended reading
Please note that Internet Explorer version 8.x will not be
supported as of January 1, 2016. Please refer to this blog post
for more information.
CloseScienceDirectJournalsBooksRegisterSign inSign in
using your ScienceDirect credentials
Username
Password
Remember me
Forgotten username or password?Sign in via your
institutionOpenAthensOther
institutionHelpJournalsBooksRegisterSign inHelpcloseSign in
using your ScienceDirect credentials
Username
Password

Remember me
Forgotten username or password?Sign in via your
institutionOpenAthensOther institutionDownload PDF
Opens in a new window. Article suggestions will be shown
in a dialog on return to ScienceDirect.
Help Direct export Export file RIS (for EndNote, Reference
Manager, ProCite)
BibTeX
Text
RefWorks Direct Export
Content Citation Only
Citation and Abstract
Advanced search
JavaScript is disabled on your browser.
Please enable JavaScript to use all the features on this
page.

Sleep Medicine Reviews
Available online 25 September 2016
In Press, Corrected Proof — Note to users
183846||Clinical Review
Memory consolidation in sleep disordersNicola Cellinia, b, , a
Department of General Psychology, University of Padova,
Padova, Italyb Department of Psychology, University of
California, Riverside, CA, USAReceived 2 February 2016,
Revised 18 September 2016, Accepted 19 September 2016,
Available online 25 September 2016

Summary
In recent years sleep-related memory consolidation has become
a central topic in the sleep research field. Several studies have
shown that in healthy individuals sleep promotes memory
consolidation. Notwithstanding this, the consequences of sleep
disorders on offline memory consolidation remain poorly
investigated. Research studies indicate that patients with
insomnia, obstructive sleep apnea, and narcolepsy often exhibit
sleep-related impairment in the consolidation of declarative and
procedural information. On the other hand, patients with
parasomnias, such as sleep-walking, night terrors and rapid eye
movement (REM) behavior disorder, do not present any memory
impairment. These studies suggest that only sleep disorders
characterized by increased post-learning arousal and disrupted
sleep architecture seem to be associated with offline memory
consolidation issues. Such impairments, arising already in
childhood, may potentially affect the development and
maintenance of an individual's cognitive abilities, reducing their
quality of life and increasing the risk of accidents. However,
promising findings suggest that successfully treating sleep
symptoms can result in the restoration of memory functions and
marked reduction of direct and indirect societal costs of sleep
disorders.
KeywordsArousal; Continuous positive airway pressure (CPAP);
Insomnia; Memory consolidation; Motor skills; Narcolepsy;
Obstructive sleep apnea; Sleepwalking; Rapid eye movement
(REM) sleep
AbbreviationsAHI
apnea-hypopnea indexASRT
alternating serial reaction time taskCPAP
continuous positive airway pressureFTT
finger tapping taskNREM
non-rapid eye movementNC
narcolepsy with cataplexyMA

motor adaptationMSL
motor sequence learningMTT
mirror tracing taskOSA
obstructive sleep apneaPSG
polysomnographyRBD
REM behavior disorderROCFT
Rey–Osterrieth complex figure testREM
rapid eye movementSOREM
sleep onset rapid eye movementSMR
sensorimotor rhythmSWA
slow wave activitySWS
slow wave sleepTDT
texture discrimination taskWAIS
Wechsler adult intelligence scaleWPA
word-pair association task
Introduction
Memory consolidation, the process by which labile information
becomes stronger, more efficient, and more resistant to
interference [1], is purported to occur during offline periods
after encoding. As already observed in a pioneering study in
1924 by Jenkins and Dallenbach [2], this process seems to be
facilitated when learning is followed by a sleep period.
However, only in recent years has extensive research indicated
that an intervening period of sleep after learning promotes the
offline consolidation of declarative, perceptual, emotional, and
procedural information [3]. Consequently, if sleep affects
memory consolidation, it is reasonable to hypothesize that
disturbed and/or altered sleep, as experienced by individuals
with sleep disorders, may impair the ability to optimally
consolidate information. Further, it has been estimated that
about 45 million individuals in Europe [4], and between 50 and
70 million in the US suffer from sleep disorders [5], but very
few research studies have investigated the consequences of
sleep disorders on offline memory consolidation abilities. Yet,
understanding the cognitive consequences of sleep disorders

holds far-reaching implications for both future neuroscientific
investigations as well as for clinical purposes. Nonetheless,
only one review by Cipolli and colleagues [6] has been
published on this topic. In that review, the authors supported
the idea of an impaired memory consolidation process in
patients with sleep disorders. The current review aims to
present and integrate the newly available findings regarding
sleep disorders and memory consolidation with the studies
described in Cipolli and colleagues' work [6], providing a guide
for future investigations trying to understand how memory
impairments might be reduced via treatments targeting the sleep
symptomatology, and thus, facilitating the translation from
basic research to clinical practice.
The present review is organized as follows. First, I will briefly
describe the main theoretical models regarding sleep and
memory consolidation. Next, I will review all the available
studies on sleep disorder and memory consolidation presented
by type of disorder (i.e., insomnia, obstructive sleep apnea,
narcolepsy, parasomnias) and the chief results will be outlined.
Subsequently, these results will be discussed within a
comprehensive perspective on how memory consolidation is
affected by sleep disturbances. In the final section, clinical
implications will be advanced and discussed.
Sleep and memory consolidation
Offline memory consolidation is typically assessed comparing
performance in a memory task before and after a period of time
that includes sleep and/or wakefulness. Several theoretical
models have been proposed to explain the role of sleep in the
consolidation of information. Beyond the dual process
hypothesis [7] and the opportunistic consolidation theory [8],
the models that so far have attracted the most interest in sleep
research are the active system consolidation model [1] and the
synaptic homeostasis hypothesis [9].
The active system consolidation model [1], based on the two-
stage model of memory trace formation [10], proposes that

PSYC 380Research Paper Grading RubricStudentCriteriaPoi.docx

PSYC 380Research Paper Grading RubricStudentCriteriaPoi.docx

Recommended

Recommended

More Related Content

Similar to PSYC 380Research Paper Grading RubricStudentCriteriaPoi.docx

Similar to PSYC 380Research Paper Grading RubricStudentCriteriaPoi.docx (20)

More from potmanandrea

More from potmanandrea (20)

Recently uploaded

Recently uploaded (20)

PSYC 380Research Paper Grading RubricStudentCriteriaPoi.docx