Description about chronobiology, circadian rhythm and circadian rhythm disorders.

1. Presenter : Dr. Tesita
Sherry
Moderator : Dr. S.
Arun
CHRONOBIOLO
GY

2. INTRODUCTION:
 Chronos= time; biology=study of life
 Chronobiology is a field of biology that examines
periodic(cyclic)phenomena in living organisms
and their adoptation to solar and lunar related
rhythms.

3. These occur:-
1. In animals (eating, sleeping, mating,
hibernating, migration, cellular regeneration
etc.)
2. In plants (leaf movements, photosynthetic
reactons etc.)
3. In microbial organisms such as fungi and
protozoa.
The most important rhythm in chronobiology is
the circadian rhythm.

4. Chronobiological Terms:
 Biological clock:- - the internal
physiological systems that track the
environmental rhythms. Responsible for
generating biological rhythms.
 Biological rhythm:- is one or more
biological events or functions that reoccur in
time in a repeated order and with a repeated
interval between occurrence.
 Circadian rhythm:-Cyclical variation in a
metabolic, physiological or behavioral

5.  Circannual rhythm:-Cyclical variation in a
metabolic, physiological or behavioral
process with a period of about an year.
 Entrainment:-Synchronization of one
biological rhythm to another or to a zeitgeber
cycle, e.g. circadian rhythm are often
entrained to the lightdark cycle.
 Oscillator:-Internal and therefore unseen,
or endogenous oscillator (the biological clock
) that produces an overt measurable biological
rhythm in the organism.

6.  Period:-The length of one complete cycle
of a rhythm
 Phase:-A particular reference point in the
cycle of a rhythm, e.g. the daily onset of
locomotor activity, or the light-to-dark
transition in a zeitgeber cycle.
 Phase shift:-Shift in a biological rhythm
along its time axis so whilst the period
remains the same the time at which the
rhythm occurs changes
 Zeitgeber(“time giver”):-Periodic
environmental signal that entrains some

7. BIOLOGICAL CLOCKS:
 "biological clocks" - the internal
physiological systems that track the
environmental rhythms. Responsible for
generating biological rhythms
 True biological clocks has 4 characteristics
1. The clock is endogenous, meaning it
gives the organism an innate ability to
maintain periods of a particular length
between biological functions.

8. 2. The clock is temperature independent—a
very unusual situation in biology but an
essential characteristic to avoid biological
rhythms being governed by the weather.
3. Biological clocks have the ability to be reset in
order to maintain a relationship with
environmental cues.
4. Biological clocks are an internal continuous
monitor of the passage of time, allowing the
organism to keep track of duration biologically.

9. CLOCK:
Functions:
1. The capacity of the biological clock to free
run (operate without external cues),
2. The ability of timing signals, known as
Zeitgeber (German for "time-giver"), to
synchronize the cycles to the
environmental signals.(Any external or
environmental cue that entrains, or
synchronizes, an organism's biological
rhythms to the earth's 24-hour light/dark
cycle and 12 month cycle)

10.  Common zeitgebers include light, temperature,
and social cues such as clocks, sound, or
physical contact.
 A biological clock is said to be free running when
these external cues are removed.
 The average free run period for circadian
rhythms in humans is 25 hours.
 Thus, if isolated from outside input, people tend
to go to sleep one hour later each day, quickly
becoming out of sync with the rest of the 24
hour-based human world.

11. BIOLOGICAL RHYTHM:
 Biological rhythm is one or more biological
events or functions that reoccur in time in a
repeated order and with a repeated interval
between occurrence.
 These are the ways that organisms adapt and live
with the environmental rhythms around them,
such as the spin of the earth, the movement of
the earth around the sun, and movement of the
moon around the earth.

12. TYPES:
 Two types- exogenous and endogenous.
 Exogenous biological rhythms are driven
directly by the environment or another external
influence. Eg. the hopping of sparrows on a perch
when a light is turned on.
 Endogenous biological rhythms are driven by
internal biological clocks and are maintained even
when environmental cues are removed. Eg. the
wake-sleep cycle and the daily body temperature
cycles.

13. BIOLOGICAL RHYTHMS:

14. CIRCADIAN RHYTHMS:
 Latin: circa=about; dies=day
 The most extensively studied and best
understood biological rhythms.
 Rhythms that fluctuate on a 24-hour time scale
are known as circadian rhythms.
 Physiologic or behavioral cycles with a period of
24 hrs produced by endogenous pacemaker.
 Franz Halberg who coined the word circadian, is
widely considered the "father of American
chronobiology.“
 The best-known circadian rhythms:
1. Body temperature
2. Hormone secretion
3. Metabolism

15. PROPERTIES:
 Ubiquitous (Seen in cyanobacterias, plants,
rodents, humans)
 Endogenous (persist in the absence of
environmental cycles)
 The rhythm can be reset by exposure to external
stimuli (such as light and heat), a process called
entrainment
 Circadian rhythm can further be broken down into
routine cycles during the 24-hour day:
Diurnal- which describes organisms active
during daytime
Nocturnal- which describes organisms active
in the night
Crepuscular- which describes animals

16. ENTRAINMENT:
 Entrainment is the process of aligning a biological
rhythm with an environmental stimulus.
 There are limits to the time periods that biological
rhythms can be entrained.
 For circadian rhythms in most animals, 18 hours
is the shortest period tolerated, with an upper limit
of about 28-30 hours.
 If zeitgebers are provided for shorter or longer
intervals, the organism reverts back to free
running.
 Example of entrainment is the acquisition of the
24-hour wake-sleep schedule by human infants
after birth. Newborn circadian rhythms free
run, significantly disrupting the sleeping patterns
of their parents. However, as they mature and
become responsive to zeitgebers such as light

17.  Prominent daily variations also occur in
1. Endocrine,
2. Thermoregulatory,
3. Cardiac,
4. Pulmonary,
5. Renal,
6. Gastrointestinal,
7. Neurobehavioral functions.

18. Pulsatile exocrine and endocrine
secretions dependent on human
circadian rhythm.

19.  Measurement of circadian phase and its
changes can be obtained through the
assessment of proxymarkers which are:
 Core body temperature minimum(CBTM) –
which occurs approximately 2 hrs before
awakening from nocturnal sleep.
 Dim light melatonin onset (DLMO)- the time
at which endogenous melatonin begins to
climb which takes place approximately 2-3 hr
before routine bedtime.

20. HUMAN CIRCADIAN RHYTHMS: Sleep-wake
cycle
 Body
temperature
 Behaviour
 Food and water
intake
 Hormones
 Metabolism
 Body fluids
 Expression of

21. CIRCADIAN AXIS:
 The circadian axis of mammals can be divided
into three distinct functional components:
1. A master pacemaker situated in
the SCN.
2. Afferent--A photoreceptive input to
the SCN that originates in the eye.
3. Efferent--The myriad of rhythmic
outputs that provide insight into the
clockwork of the circadian pacemaker.

22. CIRCADIAN PACEMAKERS:
 The SCN is the master
oscillator
 They are small, paired,
hypothalamic structures
situated immediately
dorsal to the optic chiasm.
 Master oscillator--
generates the mean
circadian rhythm and
orchestrates a multitudes
of slave oscillators found in
peripheral tissues like
kidney, liver, lungs & other
sites of the brain.
 The neurons of the SCN
are among the smallest
neurons in the entire brain.

23.  The SCN is active during the
day in both diurnal and
nocturnal animals.
 The SCN tells the animal
whether it’s day or night, but not
how to behave.
 Transplantation of SCN tissue
from mutant hamsters that
expressed abnormally short
circadian periods into the brains
of SCN lesioned host hamsters
with normal prelesion circadian
periods resulted in a transfer of
the abnormally short period.
 SCN is a true biological

26. NEURO PHYSIOLOGY:
 The mean circadian period generated by the
human SCN is approximately 24.18 hours.
 Like a watch that ticks 10 minutes and 48
seconds too slowly per day, an individual with
such a period gradually comes out of synchrony
with the astronomical day.
 In slightly more than 3 months, a normally diurnal
human would be in antiphase to the day–night
cycle and thus would become transiently
nocturnal.
 Therefore, a circadian clock must be reset on a
regular basis to be effective at maintaining the
proper phase relationships of behavioral and
physiological processes within the context of the

27.  The circadian clock drives many rhythms,
including rhythms in behavior, core body
temperature, sleep, feeding, drinking, and
hormonal levels.
 One such circadian-regulated hormone is the
indoleamine, melatonin.
 Melatonin synthesis is controlled through a
multisynaptic pathway from the SCN to the pineal
gland.
 Exposure to light elicits two distinct effects on the
daily melatonin profile.
 First, light acutely suppresses elevated melatonin
levels, immediately decreasing them to baseline
levels
 Second, light shifts the phase of the circadian

28.  Because melatonin can be assayed easily, it
provides a convenient window into the state of
the circadian pacemaker.
 Any perturbation of the clock is reflected in the
melatonin profile; thus, melatonin offers an output
that can be used to study the regulation of the
central circadian pacemaker

29. HORMONAL CIRCADIAN
RHYTHMS:
 Cortisol--Release is highest in the
morning and drops during the day.
 Glutamate--Released by the
retinohypothalamic tract during light
 Melatonin--Released only at night (by
the retina and the pineal gland).

30.  Growth hormone –increase during
sleep; decrease during wakeful state.
 Prolactin –resembles like growth
hormone cycle.
 Aldosterone – peaks in afternoon;
declines in evening.
 Testosterone – low in afternoon; high in
night

31.  The products of the Per
and Cry genes
translocate back into the
nucleus and repress their
own transcription.
 This series of events
constitutes the negative
feedback limb of the core
oscillation.
 light directly influences
the molecular clock via its
impact on the expression
of Per2, which has either
phase advancing or
delaying effects on the
Molecular clockwork:

32. RESETTING THE CIRCADIAN
CLOCK:
 The mean circadian period generated by the
human SCN is of about 24.18 hours.
 In human light is the most effective agent for
entraining the circadian system.
 Bilateral removal of eyes– incapable to reset
circadian clock, indicating that the photosensitive
apparatus necessary for resetting must be ocular.
 To maintain the proper phase relationship of
behavioral and physiological process circadian
clock should be resetted in a regular basis within

33.  Photosensitive apparatus required for resetting
the circadian clock is different from the
photoreceptors rods or cones.
 The light intensity required to activate such
apparatus having high threshold is of low i.e. 3
log unit for longer duration than of visual system.
 Eyes may retain the function in clock resetting
despite being useless for vision.

34. EXTRAOCULAR
PHOTORECEPTION:
 Photic stimulation of extraocular tissue is
sufficient to shift the human circadian clock.
 blue light illumination of highly vascularized
tissue, such as the popliteal region behind the
knee, was shown to phase shift the nightly
increase of melatonin.
 Currently this is not widely accepted and further
research is needed.

35. NOVEL CLASS OF RETINAL
PHOTORECEPTORS:
 Studies in blind human and retinally degenerate
animals– photoreceptors other than rods and cones are
likely to be involved in circadian system
 Rodent retinal ganglion cells found to be intrinsically
photosensitive
 These cells contain Melanopsin– photo pigment initially
discovered in melanophores of tadpoles– later identified
in human retina
 Melanopsin is also localized in plasma membrane of cell
body, axon and dendrites
 Plays important role in phase shifting of circadian

36. SLEEP AND CIRCADIAN RHYTHMS:
SLEEP REGULATION
Sleep is the integrated product of two oscillatory
processes.
1. Sleep homeostat:
Related to the accumulation and dissipation of sleep
debt.
Adenosine is supposed to be a neuromodulator of the
sleep homeostat.
2. Circadian cycle/clock:
Controls a daily rhythm in sleep propensity or
conversely, arousal.
Arousal steadily increases throughout the day,

37.  Experiments imposing forced sleep schedules
throughout the circadian day have shown that an
uninterrupted 8-hour bout of sleep can only be
obtained if sleep is initiated approximately 6 hours
before the temperature nadir.
 This nadir typically occurs at approximately 5:00 AM
to 6:00AM.
 In healthy individuals, initiating sleep between 11:00
PM and 12:00 AM affords the highest probability of
getting 8 solid hours of sleep.
 Adult short sleepers habitually get 5-6 or fewer hours
of sleep per 24 hours, without impairment in daytime
functioning. Their sleep is typically unbroken and,
although short, is not a result of voluntarily restricted

38.  A “long sleeper” is an individual who sleep longer
than average, but feels well and functions without
impairment. Long sleep is different from idiopathic
hypersomnia where a person sleeps long hours
but still does not feel refreshed. Long sleepers
are adults who typically sleep 9-10 hours (or
more) when not previously sleepdeprived, and
children who sleep 2 hours more than the age-
appropriate norm.

39. CIRCADIAN RHYTHMS SLEEP
DISORDERS:
 Defined as an alteration of the phase
relationship between the intrinsic
circadian system & the extrinsic light-dark
cycle resulting in an unconventional or
abnormal sleep-wake pattern.
 leads to symptoms of insomnia
,excessive sleepiness or impairment of
occupational/academic/social functioning.

40. 6 RECOGNIZED DISORDERS:
Alteration of
endogenous
circadian system
Change in timing of
environmental light-dark or
social activity
cycles(circadian
desynchrony) Delayed sleep phase
Syndrome
 Advanced sleep
phase syndrome
 Non 24hr sleep-wake
syndrome
 Irregular sleep-wake
rhythm
 Shift work sleep
disorder
 Jet lag disorder

41. DELAYED SLEEP PHASE
SYNDROME (DSPS):
 A circadan sleep disorder in which the individual’s
internal body clock is delayed with respect to
external day/night cycle.
 Falls asleep late at night, typically between
1:00am and 6:00am and awakens in the late
morning or in the afternoon.
 Delayed sleep phase syndrome (DSPS) has been
shown to be influenced by genetics.
 A length polymorphism in a repeat region of the
hPER3 gene appears to be associated with
diurnal preference in DSPS patients, the shorter
allele being associated with evening preference.
 Functional impairment is seen in daytime if total

42.  Diagnosis by stable sleep delay in at
least 1 week of sleep log along with
delay in CBTM & DLMO with exclusion
of other causes.
 Prevalence of 5-10% and more common
in adolescents & young adults.
 Unusually long endogenous circadian
period that maintains its entrainment
may be the underlying patho-physiology.

43. MANAGEMENT:
 Light therapy for 2 wks with 2500 lux given for 2 hrs
b/w 6 – 9 am with evening light restriction showed an
improvement in multiple sleep latencies.
 Melatonin given at night time at a dose of 5 mg for 6
wks 5 hrs before the mean sleep onset time.
 Vit B12 has been reported as effective in advancing
sleep phase.
 Avoidance of napping to enhance homeostatic drive to
sleep during the night and avoidance of bright light
exposure in evening hrs.

44. ADVANCED SLEEP PHASE
SYNDROME (ASPS):
 It is a pathological extreme of the morning lark
phenotype.
 An autosomal-dominant familial form of ASPS
(FASPS) recently has been genetically
characterized.
 Afflicted family members exhibit a striking 4-hour
advance of the daily sleep–wake rhythm.
 They typically fall asleep at approximately 7:30

45.  Affected individuals have a single nucleotide
polymorphism in the gene encoding hPER2, the human
homolog of the mouse Per2 clock gene.
 Functional impairment occur in the late afternoon &
evening when sleepiness begins.
 Diagnosis include confirmation of advanced timing of
sleep period with a sleep log for 7 days with
exclusion of other causes.
 Prevalence is about 1 % in middle aged individuals
,appears more common with advancing age.
 Elderly vulnerable to reduction of light transmission

46. MANAGEMENT:
 Light therapy used in the evening to delay the
circadian phase eg. 4000 lux artificial light source
over 12 consecutive days from 7 – 9 pm resulted in
decreased awakenings and phase advancement.
 Only drawback is compliance with usage of bright
light boxes in older subjects
 Melatonin taken in the morning delays the sleep
schedule but side effects may limit this use.
 Most efficacious is chronotherapy in which sleep
onset is advanced 3 hrs at a time to an interval of 2
days until desired sleep-wake cycle timing is obtained

47. Non 24hr sleep-wake syndrome:
 Circadian rhythm that free runs at a period of its
endogenous circadian clock even in the
presence of time cues. So, sleep wake period
gradually shifts to later in day as time advances.
 Hallmark is the episodic symptom presentation
depending on the phase of patient’s clock at any
given time. If the phase is out of sync with the
desired sleep-wake cycle ,symptoms are
maximum but if phase identical, then symptoms
are not present at all.
 Diagnosis by progressively delayed sleep-wake

48.  Most common in blind because light signals
fail to transmit to SCN. In sighted, secondary to
diminished sensitivity to light as an entraining
agent or exceedingly long intrinsic circadian
rhythm.
 Melatonin dosed at 0.5 mg-10mg at night within
an hr of bed time over 1-3 wks in the blind. In
sighted. artificial light given may be effective in
slowing down the clock.
 vitamin B12 has been reported to be effective

49. IRREGULAR SLEEP-WAKE
DISORDER (ISWD):
 Lack of clearly distinct sleep-wake cycles
resulting in symptoms of insomnia or sleepiness.
 Nighttime sleep is truncated and shows poor
consolidation,daytime has frequent,irregualar
napping.
 Total amount of sleep over 24 hrs is normal ,but
sleep tends to be divided into among 3 or more
erratic sleep periods
 Sleep logs shows at least three irregular sleep
bouts during 24-hr period over a week.
 M/c in institutionalised patients with dementia & in
children with MR

50. CIRCADIAN DESYNCHRONY:
 Desynchrony between and among the SCN and
the various oscillators in peripheral tissues result
in circadian-associated maladies.
 Travel across multiple time zones (jet-lag) and
shift work are the most common causes of
circadian desynchrony.
 Cardiovascular disease risk factors such as
obesity, low high-density lipoprotein (HDL)
cholesterol levels, and high triglycerides are more
prevalent among shift workers than day workers.
Furthermore, many of these associations
increase in aged shift workers.
 Epidemiological studies have shown that women

51. JET LAG:
 When a person travels through the different time
zones ther would be the phase difference.
 In jet lag the clock is slow to reset, so that after
time zones have been crossed, the endogenous
signals for sleep and wakefulness do not match
the local light–dark and social schedules.
 It is not linked to the length of flight, but to the
trans-meridian (west–east) distance traveled.
 Eg: A ten-hour flight from Europe to southern
Africa does not cause jet lag, as travel is primarily
north–south. A five-hour flight from the east to the
west coast of the United States may well result in
jet lag.

52.  Travelling from east to west will have phase
advance while reverse would be in opposite
direction.
 To catch up with local time upon eastward travel,
a phase advance must occur whereas a phase
delay occurs in westward travel. Since phase
advances are more difficult than phase delays ,
eastward travel is more difficult.
 Air travellers who fly west typically complain of
difficulty maintaining sleep & early morning
awakenings whereas those flying east have
difficulty with initiating sleep.
 Symptoms include reduced alertness, day time
fatigue, loss of appetite, reduced cognitive skills
and disruption Of sleep/wakefulness , headaches
, fatigue , irregular sleep patterns, insomnia ,

53. MANAGEMENT:
 Before the flight-
1. To visit the doctor to plan a coping strategy for
medical conditions that require monitoring &
regarding meds.
2. Attempt to partially adapt to the destination time
zone in advance by starting the daily routine one
hour before or after one normally does during the
week before departure.
 During the flight-
1. Not to take alcoholic beverages and caffeine, as
caffeine disrupts sleeping schedules & to drink
plenty of water.
2. To break the trip into smaller segments if it is too
long and stay overnight in some city. Also, to adjust
sleeping times in plane to destination time.

54.  Upon arrival- to adapt to the local time and eat
accordingly. Also, exposure to sunlight during
the day is helpful.
 The recommended dose of melatonin is 0.3–0.5
mg, to be taken the first day of traveling.
 Light therapy can speed up to one hour per time
zone when used at the correct time, combined
with avoiding light during specific periods.

55. SHIFT-WORK DISORDER:
 Artificial lighting has permitted the manufacturing
and service industries to work around the clock.
As a result, shift workers are constantly
experiencing the effects of circadian desynchrony
as they try to entrain to an ever-changing light–
dark cycle.
 Deleterious effects of shift work include elevated
stress, deficits in alertness, decreased cognitive
function, and gastric distress. Prevalence of
about 10% in night shift workers.
 Diagnostic criteria include either insomnia or
excessive sleepiness , temporal relationship with
work , present for at least 1 month,7-day sleep
log or actigraph revealing disturbed sleep
circadian/sleep alignment.

56.  Total sleep time is reduced, reporting 10 fewer sleep
hrs/week.Shift workers fail to delay their circadian rhythm
b’cos of exposure to bright light in morning.
 At increased risk of development of disease in other organ
systems.
MANAGEMENT:
 Exposure to bright light during nighttime work shift has
been efficacious.Light exposure between 7000 & 12000
lux during night and complete darkness during day on
subjects for 1 week.
 Intermittent exposure to light of 20 min/hr appears to be
effective in producing desired phase shifts in night
workers.
 Exogenous melatonin is used by shift workers during the
morning to improve the timing & quality of sleep.
 Modafinil (wakefulness promoting agent)is approved for

57. PREMENSTRUAL SYNDROME:
 M/C monthly cycle in humans is the menstrual cycle linked
with changes in the mental state.
 Premenstrual syndrome : recurrence of symptoms in the
pre – menstruum 5-10 days (luteal phase) with absence in
the postmenstruum (follicular phase). Seen in 30-80% of
reproductive women.
 Psychological symptoms : disabling tension , severe &
sudden mood swings , suicidal depression and
incapacitating lethergy
 Physical symptoms : headache , bloated feeling , loss of
energy , cyclic acne
 It is the timing rather than the nature of symptoms that
indicates the diagnosis. To establish a pattern, keep a
prospective record of her symptoms on a calendar for at
least two menstrual cycles. PMS has increased risk for

58. MANAGEMENT:
 Supportive therapy includes evaluation, reassurance,
and informational counseling.
 Healthy lifestyle: Reduction of caffeine, sugar, and
sodium intake and increase of fiber, adequate rest and
sleep with aerobic exercise. Dietary intervention
studies indicate that calcium supplementation, vitamin
E (400 IU/d) has shown some effectiveness along with
Vitamin B6, magnesium, manganese and tryptophan.
 SSRIs can be used to treat severe PMS ,medication
taken only on the days when symptoms are expected
to occur.
 Spironolactone has been shown to be useful for water
retention.
 NSAIDs; e.g., ibuprofen have been used to treat pain.

59. CIRCADIAN VARIATION IN
PSYCHIATRY:
 Early morning awakening & mood most
depressed in morning phase advance of sleep
wake cycle.
 REM sleep occurs earlier in the night in
depression along with changes of body
temperature & cortisol levels.
 Travel from east to west can cause depression
and from west to east can cause hypomania.
 Shortened rhythm of less than 24 hrs seen in long
term schizophrenia

60. SEASONAL AFFECTIVE
DISORDERS:
 SAD is the most overt manifestation of
seasonality in humans.
 It is characterized by recurrent major depressive
episodes followed by periods of remission that
occur on a seasonal basis.

61. SAD sepcifier criteria are:
A. Regular temporal relationship between the
onset of major depressive episodes and a
particular time of the year.
B. Full remissions (or a change from depression to
mania or hypomania) also occur at a
characteristic time of the year.
 Two major depressive episodes meeting criteria A
and B have occurred in the last 2 years, and no
non seasonal episodes have occurred in the
same period.

62. WINTER SDA:
 Called as winter depression or winter blues.
 Onset in the late fall and early winter and remits
in the late winter and early summer.
 Symptoms may be atypical to major depression
Significant increase in weight
Increase rather than decrease in sleep
Hyperphagia
Heightened sensitivity to interpersonal rejection
Leaden feeling in the extremities.

63.  Incidence
4-9% of total population
20% of population may have sub syndromal features.
 M: F=1:4
 Runs in families showing genetic or environmental
influences
Serum level of melatonin is considered as causative
condition.
 Treatment
 Light therapy
 High irradiance(5,000 -10,000 lux) for about 45 – 90
minutes.
Early morning or evening pattern of exposure.
 Pharmacotherapy
MAO inhibitors.

64. NON SEASONAL
DEPRESSION:
 Aberrations in the timing and amount of sleep are
frequently part of the symptomology of depression,
including nonseasonal depression.
 For example, the circadian phase angle of sleep
onset can vary in bipolar I disorder, depending on the
state; depression causes a phase delay, whereas
mania results in a phase advance.
 In addition, sleep disturbances can contribute to the
pathogenesis of the disease

65.  A curious phenomenon related to depression and
sleep is that total sleep deprivation can provide a
transient antidepressant effect in a majority
(approximately 60 percent) of depressed patients.
 Relapse occurs after the following night of sleep.
 Even short, daytime naps can cause relapse.
 This tendency of nap-induced relapse varies as a
function of the time of day during which the nap is
taken.
 Early morning appears to be a critical time during
which naps have a high tendency of causing relapse.

66. SEASONALITY IN
PSYCHIATRY:
 A peak in the rate of suicide occurs in the summer
 Birth rates also tend to show a small but distinguishable peak
in spring and summer.
 In schizophrenia , patients show an excess of birth dates in
the winter months in northern & southern hemispheres.
 Higher rate of psychiatric admissions in summer months
 Depression and ECT more in spring & autumn.
 Female manic patients peak admissions in Aug & Sep.

67. RELEVANCE IN MEDICAL
CONDITIONS:
 Obesity and
metabolic
dysfunction
 Cancer
 Effect of aging

68. Obesity and metabolic dysfunction:
 Experimental studies showed the relation
between blood lipid, glucose, and insulin
level with the circadian rhythm.
 Shift workers have more incidence of
having metabolic syndrome characterized
by:
Hyperglycemia
Hypoinsulinemia
Dyslipidemia
Visceral obesity and the complications

69. Cancer:
 Experimental studies showed the increased
incidence of carcinomas in jet laged- radiation
exposed animals.
 Shift working females and airhostess crossing
the meridians were found to be increased risk
of breast cancer.
 Long-term shift work also have shown to be
correlated with increased incidence of
colorectal and breast cancer.
 Supposed to be inhibition of melatonin which

70. Aging:
 Experimental studies showed that phase
shifting has effect in survival of aged
mice in which phase delay increased the
survival but phase advance decreased
the survival.
 During aging circadian period shortens
with phase advance resulting in earlier
bedtime and waking.

71. DRUG DRUG EFFECT ON RHYTHM
TCA Decreases elevated nocturnal body
temperature in depressive patients
SSRI Decreases elevated nocturnal body
temperature in depressive patients.
Augment
diurnal activities.
LITHIUM Inhibit glycogen synthase kinase 3b
which stabilizes the negative clock work
stabilizer REV-ERBa—lengthens the
cercarion period.
BENZODIZE
PINES
(short acting)
Act via GABA receptors in SCN- induces
circadian phase advances
Brotizolam has been shown to reduce

73. THANK
YOU