Circadian rhythms are 24-hour biological cycles that regulate various bodily functions like sleep-wake cycles, temperature regulation, and hormone secretion. They are controlled by a master clock in the brain and influenced by environmental cues like light exposure. Disruptions to circadian rhythms can cause sleep disorders like delayed sleep phase syndrome where one's sleep schedule is delayed by 2+ hours, or non-24 hour sleep-wake disorder where the circadian rhythm follows a 25-27 hour cycle. Shift work and jet lag are also considered extrinsic circadian rhythm disorders.

1. CIRCADIAN RHYTHM

2. The term "circadian", was coined by Franz Halberg

3. ⚫The term circadian comes from two Latin
words namely
“circa” means around
“diem/dies” means day
Circadian means “approximately one day’’

4. ⚫4th century BC - Androsthenes
⚫13th century - The observation of a
circadian or diurnal process in humans is
mentioned in Chinese medical texts .
⚫1729 - The first recorded observation of
an endogenous circadian oscillation by the
French scientist Jean-Jacques d'Ortous de
Mairan

5. ⚫1896 - Patrick and Gilbert observed that
during a prolonged period of sleep
deprivation, sleepiness increases and
decreases with a period of approximately 24
hours.
⚫1918 - J.S. Szymanski showed that animals
are capable of maintaining 24-hour activity
patterns in the absence of external cues.
⚫1994 - Joseph Takahashi discovered the
first mammalian 'clock gene' (clock) using

6. CIRCADIAN RHYTHM
A 24-hour biological rhythm
controlled by a “pacemaker” in the brain
that sends messages to other systems
in the body. Circadian rhythm
influences various regulatory
functions, including the sleep–wake
cycle, body temperature
regulation, patterns of activity such as
eating and drinking, and hormonal and
neurotransmitter secretion.

7. 1. Circadian rhythm are 24-hour cycles that are part of the
body’s internal clock, running in the background to carry
out essential functions and processes. One of the most
important and well-known circadian rhythms is the sleep-
wake cycle.
2. Different body systems follow circadian rhythms
synchronized with a master clock in the brain. This
master clock is directly influenced by environmental
cues, especially light, which is why circadian rhythms are
tied to the day and night cycle.
3. When properly aligned, a circadian rhythm can promote
consistent and restorative sleep. But when this circadian
rhythm is thrown off, it can create significant sleeping
problems, including insomnia. Research is also revealing
that circadian rhythms play an integral role in diverse
aspects of physical and mental health.

8. ⚫Zeitgebers induce changes in the
concentrations of the molecular
components of the clock to levels
consistent with the appropriate stage
in the 24-hour cycle, a process
termed entrainment.

10. BIOLOGICALMARKERS
The classic phase markers for measuring
the timing of a mammal's circadian
rhythm are:
⚫melatonin secretion by the pineal gland
⚫core body temperature
⚫plasma level of cortisol

11. Effects of age on Circadian rhythm
 Newborn baby -16 to 20 h
 Child - 10 to 12 h
 Age 10 - 9 to 10 h
 Adolescence - 7 to 7.5 h
A gradual decline to about 6.5 h develops
in late adult life.
35 years of age onward, women tend to
sleep slightly more than men

12. Phases of the sleep cycle
 The human body cycles through two phases of sleep, (1) rapid eye
movement (REM) and (2) non-rapid eye movement (NREM) sleep, which
is further divided into three stages, N1-N3. Each phase and stage of sleep
includes variations in muscle tone, brain wave patterns, and eye
movements. The body cycles through all of these stages approximately 4 to
6 times each night, averaging 90 minutes for each cycle.
 Sleep quality and time spent in each sleep stage may become altered by
depression, aging, traumatic brain injuries, medications, and circadian
rhythm disorders. The pathophysiology associated with each will be
discussed later in detail.

13. Stages of the sleep cycle
 Sleep occurs in five stages: wake, N1, N2, N3, and REM. Stages N1 to N3 are
considered non-rapid eye movement (NREM) sleep, with each stage a
progressively deeper sleep.
 Approximately 75% of sleep is spent in the NREM stages, with the majority
spent in the N2 stage. A typical night's sleep consists of 4 to 5 sleep cycles, with
the progression of sleep stages in the following order: N1, N2, N3, N2, and
REM.
 A complete sleep cycle takes roughly 90 to 110 minutes. The first REM period
is short, and, as the night progresses, longer periods of REM and decreased
time in deep sleep (NREM) occur.

14.  Wake/Alert
 EEG recording: beta waves - highest frequency, lowest amplitude (alpha waves are seen during
quiet/relaxed wakefulness)
 The first stage is the wake stage or stage W, which further depends on whether the eyes are
open or closed. During eye-open wakefulness, beta waves predominate. As individuals become
drowsy and close their eyes, alpha waves become the predominant pattern.
 N1 (Stage 1) - Light Sleep (5%)
 EEG recording: theta waves - low voltage
 This is the lightest stage of sleep and begins when more than 50% of the alpha waves are
replaced with low-amplitude mixed-frequency (LAMF) activity. Muscle tone is present in the
skeletal muscle, and breathing tends to occur at a regular rate. This stage lasts around 1 to 5
minutes, consisting of 5% of total sleep time.

15.  N2 (Stage 2) - Deeper Sleep (45%)
 EEG recording: sleep spindles and K complexes
 This stage represents deeper sleep as your heart rate and body temperate drop. It is
characterized by the presence of sleep spindles, K-complexes, or both. Sleep spindles are
brief, powerful bursts of neuronal firing in the superior temporal gyri, anterior cingulate,
insular cortices, and thalamus, inducing calcium influx into cortical pyramidal cells.
 This mechanism is believed to be integral to synaptic plasticity. Numerous studies suggest
that sleep spindles play an important role in memory consolidation, specifically
procedural and declarative memory.
 K-complexes are long delta waves that last for approximately one second and are known
to be the longest and most distinct of all brain waves. K-complexes have been shown to
function in maintaining sleep and memory consolidation.
 Stage 2 sleep lasts around 25 minutes in the first cycle and lengthens with each successive
cycle, eventually consisting of about 45% of total sleep. This stage of sleep is when
bruxism (teeth grinding) occurs.

16.  N3 (Stage 3) - Deepest Non-REM Sleep (25%)
 EEG recording: delta waves - lowest frequency, highest amplitude
 N3 is also known as slow-wave sleep (SWS). This is considered the deepest stage of sleep and
is characterized by signals with much lower frequencies and higher amplitudes, known as delta
waves.
 This stage is the most difficult to awaken from, and, for some people, even loud noises (> 100
decibels) will not awaken them. As people age, they tend to spend less time in this slow, delta-
wave sleep and more time in stage N2 sleep. Although this stage has the greatest arousal
threshold, if someone is awoken during this stage, they will have a transient phase of mental
fogginess, known as sleep inertia.
 Cognitive testing shows that individuals awakened during this stage tend to have moderately
impaired mental performance for 30 minutes to an hour. This is the stage when the body repairs
and regrows tissues, builds bone and muscle, and strengthens the immune system. This is also
the stage when sleepwalking, night terrors, and bedwetting occurs.

17.  REM (25%)
 EEG recording: beta waves - similar to brain waves during wakefulness
 REM is associated with dreaming and is not considered a restful sleep
stage. While the EEG is similar to an awake individual, the skeletal
muscles are atonic and without movement, except for the eyes and
diaphragmatic breathing muscles, which remain active. However, the
breathing rate becomes more erratic and irregular.
 This stage usually starts 90 minutes after you fall asleep, with each of
your REM cycles getting longer throughout the night. The first period
typically lasts 10 minutes, with the final one lasting up to an hour. REM
is when dreaming, nightmares, and penile/clitoral tumescence occur.

18.  Important characteristics of REM:
• Associated with dreaming and irregular muscle movements as well as rapid
movements of the eyes
• A person is more difficult to arouse by sensory stimuli than during SWS
• People tend to awaken spontaneously in the morning during an episode of
REM sleep
• Loss of motor tone, increased brain O2 use, increased and variable pulse
and blood pressure
• Increased levels of ACh
• The brain is highly active throughout REM sleep, increasing brain
metabolism by up to 20%

19. Related Testing
 The clinical evaluation of sleep is performed using a polysomnogram, a
procedure that utilizes an electroencephalogram (EEG), electrooculogram,
electromyogram, electrocardiogram, pulse oximetry, airflow, and respiratory
effort. These tests are performed overnight and usually require a minimum of 6
hours of monitoring.
 Specifically, an EEG records brain wave patterns via small electrodes placed
on the scalp. A polysomnogram is the gold standard test for diagnosing sleep-
related breathing disorders such as obstructive sleep apnea, central sleep apnea,
and sleep-related hypoventilation/hypoxia.
 A polysomnogram may also be used to evaluate nocturnal seizures, periodic
limb movement disorder, narcolepsy, and REM sleep behavior disorder

20. CRITERIAOFA CIRCADIAN RHYTHM
To be called circadian, a biological rhythm must
meet these four general criteria:
⚫ The rhythms repeat once a day (they have a 24- hour
period).
⚫ The rhythms persist in the absence of external cues
(endogenous).
⚫ The rhythms can be adjusted to match the local time
(entrainable).
⚫ The rhythms maintain circadian periodicity over a range
of physiological temperatures; they exhibit temperature
compensation.

21. CIRCADIAN RHYTHM DISORDERS
⚫Intrinsic Circadian Rhythm Disorders.
Delayed Sleep Phase Syndrome (DSPS)
Advanced Sleep Phase Syndrome (ASPS)
Irregular Sleep-Wake Pattern
Non-24-Hour Sleep-Wake Syndrome
⚫Extrinsic Circadian Rhythm Disorders
Shift Work
Time-Zone Change Disorders

22. CIRCADIAN RHYTHM DISORDERS
The common types of circadian rhythm sleep disorders
include:
Delayed Sleep Phase Disorder: If you have this sleep disorder,
you go to sleep and wake up more than two hours later than
what is typically considered a normal sleep-wake cycle. For
example, you're a “night owl” who may not be able to fall
asleep until 2 a.m. or later, but then sleep in until as late as 3
p.m.
Other common features of delayed sleep phase disorder are:
•You're often most alert, productive, and creative
late at night.
•If forced to get up early, you are sleepy during the
day.
•You're often perceived as lazy, unmotivated, or a
poor performer who is always late for morning

23. Delayed sleep phase syndrome
⚫ First identified by Weitzman et al. (1981) as a ‘‘chrono
biological disorder with
 sleep-onset insomnia.’’
⚫ Sleep-wake circadian rhythm is delayed compared to
the time the individual attempts to sleep
⚫ Individuals report difficulty falling asleep at a desired
bedtime but have normal sleep if they attempt to sleep a
few hours later.

24. Intrinsic Circadian Rhythm
Disorders.
Intrinsic circadian rhythm disorders refer to
desynchronizes between attempts to sleep and
the sleep-wake circadian rhythm that are due
presumably to internal rather than external
causes. These disorders might result from a
weak circadian rhythm or from an inability to
entrain the rhythm to the environment.

25. Delayed sleep phase
syndrome
⚫Individuals with DSPS show late sleep
onset, few awakenings, early wake-up
times when work or social demands are
present, and late (mid afternoon) wake-up
times when there are no such demands
on their time.
⚫Delayed sleep phase individuals
commonly identify themselves as „„night
people‟‟ and report being most alert
during the late evening and night hours.

26. advanced sleep phase
syndrome
⚫Inability to stay awake until the desired
bedtime and inability to remain asleep until
the desired wake-up time.
⚫Typical sleep onset times are between 6
P.M. and 8 P.M., and no later than 9
P.M., and wake times are between 1 A.M.
and 3 A.M., and no later than 5 A.M.

27. Advanced sleep phase
syndrome
⚫ ASPS is much more common in older
individuals than in the young and the complaint of
waking up too early in the morning may be
confused with depression. The current approach to
treating ASPS is bright light exposure in the
evening and avoidance of light exposure (e.g.
wearing dark, wrap-around sunglasses) in the
morning. Bright light exposure in the evening and
the avoidance of bright light in the morning, it is
thought, help to re-entrain the sleep-wake cycle
into the circadian rhythm

28. Irregular Sleep-Wake Pattern
⚫ This rare disorder is characterized by a variable and
disorganized sleep-wake pattern that suggests the absence of
circadian rhythmicity.
⚫ Sleep is broken into several short sleep episodes, but the
cumulative sleep for a 24-hour period is at normal levels.
⚫ Polysomnographic studies show no abnormalities in sleep
parameters except for the short duration of each episode.
⚫ Common in elderly people with dementia.
⚫ Treatment consists of a gradual decrease in the number
and duration of daily naps. An increase in activity levels
and social interaction is recommended to facilitate the

29. Non-24-Hour Sleep-Wake Syndrome
⚫This is a disorder in which individuals
are unable to entrain to a 24-hour day
and instead maintain 25- to 27- hour
sleep-wake cycles. Some individuals
with this syndrome tend to
progressively phase delay. The
disorder is rare in the general
population and is assumed to have
higher prevalence among blind
people.

30. Non-24 Hour Sleep-Wake Syndrome
Other names
 Non-24
 Free runningdisorder(FRD)
 Hypernychthemeral disorder
 Circadian rhythm sleep disorder – free running type
 Circadian rhythm sleep disorder – nonentrained type
 Non-24-hour circadian rhythm disorder
 Non-24-hour sleep-wake disorder

31. Non-24-Hour Sleep-Wake Syndrome
⚫ It is a chronic circadian rhythm sleep
disorder, classified within Chapter VI, Diseases of
the Nervous System, in the ICD 10.
⚫ It can be defined as "a chronic steady pattern
comprising one- to two-hour daily delays in sleep
onset and wake times in an individual living in
society".
⚫ The pattern of delay persists literally "around the
clock", typically taking a few weeks to complete
one cycle.
⚫ This disruption of the body clock causes cyclical
bouts of nighttime sleeplessness and excessive
daytime fatigue and napping.

32. Non-24-Hour Sleep-Wake Syndrome
⚫Treatment focuses on entraining the
circadian rhythm to a 24-hour day
through social interaction, exposure to
light, and melatonin.
⚫Melatonin has been successful in
treating this disorder in blind
individuals.

33. Extrinsic Circadian Rhythm Disorders
⚫Shift Work
⚫Time-Zone Change Disorders

34. Shift Work Disorder
A disrupted sleep-wake schedule often
results in
disturbed and shortened sleep
sleepiness on the job
reduced performance levels
psychological distress due to disruptions
in family and social life.

35. Time-Zone Change Disorders

36. Time-Zone Change Disorders
⚫ Dyssomnia associated with rapid time-zone
change sdue todesynchrony between the
endogenous sleep-wake rhythm and the
light/dark cycle.
⚫ Symptoms include an inability to sustain sleep
and excessive sleepiness.
⚫ For most people, these symptoms subside after a
few days, depending on the number of time
zones crossed.

37. Time-Zone Change Disorders
⚫Frequent travelers, such as transatlantic airline
crews, may experience more persistent difficulties.
⚫Westward travel is associated with disturbed sleep
at the end of the sleep period, which coincides
with habitual wakeup time, and eastward travel is
associated with sleep onset insomnia.

38. Time-Zone Change Disorders
⚫Bright light treatment
⚫Melatonin administration about an
hour before bedtime in the new time
zone

39. Risk Groups
⚫DSP is more common in teens and young
adults, occurring at a rate of 16 percent
⚫ASP is more common as people
age, occurring in about one percent of
middle aged and older adults.
⚫Irregular sleep-wake rhythm may occur in
nursing home residents and other people
who have little exposure to time cues such
as light, activity and social schedules.

40. Risk Groups
⚫Free-running (nonentrained) type occurs
in more than half of all people who are
totally blind.
⚫Jet lag can affect anyone who travels by
air, but symptoms may be more severe
and may last longer in older people and
when anyone travels in an eastward
direction.
⚫Shift work disorder is most common in
people who work night shifts and early
morning shifts

41. Effects
⚫Sleep loss
⚫Excessive sleepiness
⚫Insomnia
⚫Depression
⚫Impaired work performance
⚫Disrupted social schedules
⚫Stressed relationships

42. TREATMENT OF CIRCADIAN
RHYTHM DISORDERS
⚫Behavior therapy or advice about sleep
hygiene.
⚫Avoid naps, caffeine, and other stimulants.
⚫Bright light therapy
⚫Blue blocking glasses therapy
⚫Medications such
as melatonin and modafinil (Provigil)
⚫Tasimelteon has been proven effective in
Phase III trials.
⚫Sleep phase chronotherapy

43. TREATMENT OF CIRCADIAN
RHYTHM DISORDERS
⚫People who suffer from delayed sleep
phase syndrome are generally unable to
reset their circadian rhythm by moving
their bedtime and rising time earlier.
⚫In sleep phase chronotherapy, an
attempt is made to move bedtime and
rising time later and later each
day, around the clock, until the person is
sleeping on a normal schedule.

44. ⚫ Here's an example of how chronotherapy could
work over a week's course of treatment, with the
patient going to sleep 3 hours later every day until
the desired sleep and waketime is reached.
(Shifting the sleep phase by 3 hours per day may
not always be possible; shorter increments of 1–2
hours are needed in such cases.)
⚫ Day 1: sleep 04:00 to 12:00
⚫ Day 2: sleep 07:00 to 15:00
⚫ Day 3: sleep 10:00 to 18:00
⚫ Day 4: sleep 13:00 to 21:00
⚫ Day 5: sleep 16:00 to 00:00
⚫ Day 6: sleep 19:00 to 03:00
⚫ Day 7 to 13: sleep 22:00 to 06:00
⚫ Day 14 and thereafter: sleep 23:00 to 07:00