Circadian RHYTHM AND DISEASES

1. Circadian Variability in Patients
with Fibromyalgia Syndrome
Dr. Ghizal Fatima
Department of Rheumatology
K.G. Medical University, Lucknow
2014

2. Circadian Rhythms
Circadian rhythms are endogenously generated, although they can be
modulated by external cues such as sunlight and temperature.
1. The rhythm has an endogenous free-running period that lasts
approximately 24 hours.
2. The rhythms are entrainable. The rhythm can be reset by exposure
to external stimuli (such as light and heat), a process
called entrainment. The external stimulus used to entrain a rhythm
is called the Zeitgeber, or "time giver".

3. Normal Circadian Rhythm
The work was done with Inkscape by YassineMrabet

4. Fibromyalgia
Fibromyalgia usually includes a broad range of symptoms including some combination of the
following:
• widespread pain
• sleep disturbances
• chronic daytime fatigue
• morning stiffness in the joints and muscles
• migraine headaches
• irritable bowel syndrome
• painful menstrual periods
• numbness or tingling of the extremities
• restless legs syndrome
• temperature sensitivity
• dizziness and balance problems
• cognitive and memory problems
• mood disturbance such as depression and anxiety

6. This condition affects mainly women, with a female-to-male
ratio of 9:1, and its estimated prevalence in various
populations varies between 2% and 5%.
Epidemiology of FMS

9. Diurnal Changes in Symptoms of Fibromalgia
(Moldofsky 1993)

10. Diurnal pattern of
Symptoms in FM. Bellamy
et al J Rheumatol 2004;31;379-389

11. Our Studies – Max Pain and Least Pain in FM

12. STIFFNESS

16. Since Symptoms follow a Rhythm like Circadian
Rhythm we studied the alteration in Circadian
Rhythm by Phillip Questionnaire
Circadian rhythm test was done using Philip
Questionnaire. (www.golite.philip.com)
The data of both patients and controls was
entered on Philip Questionnaire and it gave
the result online.

17. Circadian rhythm of Control
This graph depicts Normal circadian rhythm of healthy
control.

18. Abnormal Circadian rhythm of FMS patient
showing Faster rhythm.
This graph depicts that circadian rhythm of FMS patients is running Faster
than a normal circadian rhythm.

19. Abnormal Circadian rhythm of FMS patient
showing slow rhythm.
This graph depicts that circadian rhythm of FMS patients is running slower
than a normal circadian rhythm.

20. SCG
Pineal
gland’s
Melatonin
Rhythm
RHT
RHT=Retino-hypothalamic
neural tract
SCN=Suprachaismatic nucleus
SCG=Superior cervical ganglion
of the sympathetic nervous
system
Sleep-wake cycle, release of hormones,
temperature & other rhythmic functions
Influence of light and dark on circadian rhythm and related physiology and behavior
through the SCN (the circadian clock of the brain) in humans. The SCN generates
circadian rhythms which are synchronized to 24 hrs mostly by light. Melatonin influences
the timing and overall activity of the SCN and may also affect the function of the retina.
Melatonin
Influences
sleep
SCN
Circadian
Clock
Eye

21. Non Restorative Sleep
• Circadian rhythm sleep disorders (CRSD), a family of sleep disorders,
affect (among other bodily processes) the timing of sleep. People
with circadian rhythm sleep disorders are unable to go to sleep and
awaken at the times commonly required for work and school as well
as social needs
• Fibromyalgia has a Non Restorative Sleep and is associated with EEG
abnormalities during sleep. Less slow wave sleep. Abnormal pattern
of Alpha wave sleep.
• Slumber Vigil. Transits through dreamy states and wakefulness.

22. Is this sleep disorder related to Circadian
rhythm disorder
• Conflicting results when S. Melatonin levels are seen
• Normal levels

23. Cortisol Diurnal Variation in Mean Cortisol levels
mcg/dl in FM (Blue n=50) and Controls (Red n=50)
0
5
10
15
20
25
30
6:00 AM 12 Noon 6:00 PM 12 Mid Night
Chart Title
FM Controls

24. Diurnal Variation in Mean Melatonin levels pg/ml
in FM (Blue n=50) and Controls (Red n=50)
0
10
20
30
40
50
60
70
6:00 AM 12 Noon 6:00 PM 12 Mid Night
Chart Title
FM Controls

25. Normal
Melatonin
Levels

26. Serotonin Diurnal Variation in Mean Serotonin
levels ng/ml in FM (Blue n=50) and Controls (Red
n=50)
0
20
40
60
80
100
120
140
6:00 AM 12 Noon 6:00 PM 12 Mid Night
Chart Title
FM Controls

27. Klerman EB et al 2001 J Clin Endocrinol
Metabol 86:1034-1039.
• Did not find any evidence of a Circadian Rhythm in 10 women with
Fibromyalgia and 12 Controls
• Melatonin/Cortisol and body temp had similar profile
• Only difference was in pain and stiffness.

28. Serotonin, Substance P, & Fibromyalgia
• Schwarz et al Neuroscience Letters. Volume 259, Issue 3, 15 January
1999, 196–198.
• Harvey Moldofsky CNS Spectr 13:3 (Suppl 5) © MBL Communications
March 2008.
• Postulated that Serotonin Levelsin Brain are inversely related to
Substance P which in turn is related pain in patients with FM.

29. Conclusion
There is a Circadian Rhythm of Symptoms in Fibromyalgia
This does not appear to be related to Cortisol levels or Melatonin levels, though night time
Melatonin levels are lower.
Serotonin levels are low - this is in conformity with the hypothesis that Low Serotonin gives
rise Non restorative sleep and symptoms of Musculoskeletal Pain and Stiffness and possibly
Fatigue.
Drugs that increase Serotonin levels in brain may help. Serotonin Reuptake inhibitors may
be useful in Fibromyalgia.