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Circadian Rhythms in Health and Disease
John S. Khoury, M.D.; Karl Doghramji, M.D.
FOCUS 2014;12:45-53. doi:10.1176/appi.focus.12.1.45
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Author Information and CME Disclosure

John S. Khoury, M.D., Associate Medical Director of the Abington Memorial Hospital Sleep Disorders Center, Abington, PA

Dr. Khoury reports no competing interests.

Karl Doghramji, M.D., Professor of Psychiatry, Neurology, and Medicine, Medical Director, Jefferson Sleep Disorders Center; Program Director, Fellowship in Sleep Medicine, Thomas Jefferson University, Philadelphia, PA

Dr Doghramji reports the following disclosures: Consultant: UCB, Jazz, Teva, Vanda; Stock: Merck.

Address correspondence to: John Khoury: jskhoury@gmail.com 2325 Maryland Road, Willowgrove PA 19090.


Circadian rhythms refer to the regulation of physiology in a 24-hour cycle and are involved in our sleep-wake cycle, core body temperature, hormone secretion, hunger, mood, and more. Circadian rhythm disorders arise from a misalignment of the timing of our circadian rhythms regulated by the suprachiastmatic nucleus (SCN) and the normal sleep-wake times required to meet the demands of our daily routines. The biological markers of circadian rhythm are melatonin levels and core body temperature, although diagnosing circadian rhythm disorders is done mainly by clinical history, sleep logs, and actigraphy. Delayed sleep phase syndrome, non-24-hour sleep wake disorder, advanced sleep phase syndrome, shift work sleep disorder, and jet lag are the circadian rhythms disorders discussed in this review. Treatments for these including melatonin, light therapy, chronotherapy, and pharmacotherapy are reviewed for each. Additional studies are needed to better determine the optimal timing and dosing for melatonin for circadian rhythm disorders and for insomnia.

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Figure 1. Two Process Model Demonstrating Alignment Between Processes C and S. Sleep Drive Decreases at the Onset of Sleep, and the Circadian Rhythm is Independent of This Process.

Figure 2. Phase Response Curve for Normal Sleep, ASPS, and DSPS. Core Body Temperature Reaches its Minimum About 2 Hours Prior to Habitual Wake Up Time. DLMO Occurs About 2 Hours Before Natural Sleep Time.
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Table 1.Summary of Common Treatments Along with Their Side Effectsa
Table Footer Note

a DSPS: delayed sleep phase syndrome; ASPS: advanced sleep phase syndrome; SWSD: shift work sleep disorder. # indicates FDA-approved uses,

Table Footer Note

* indicates non-FDA-approved uses.

Table Footer Note

b Note that for nonapproved uses of melatonin and bright light therapy, the AASM has not made any specific recommendations as to timing or dosing due to insufficient evidence, and treatments listed are starting suggestions based on the authors experience within the cited guidelines.



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Sample questions:
Changes in the diagnostic formulation of insomnia in DSM-5 include which of the following:

See Doghramji: Table 1. DSM-5 Criteria for Insomnia Disorder p 6
The risk of insomnia is greatest in which of the following populations:

See Doghramji: Prevalence, p 3
A 75-year old woman requests a psychiatric consultation for frequently interrupted sleep; she falls asleep readily but awakens about six times per night, getting only about 6 hours of sleep between her bedtime of 11 p.m. and rising at 8 a.m. She is apparently in good health but is fatigued and very worried about getting inadequate sleep. A sleep laboratory study revealed no sleep disorder requiring medical management. Which of the following is the first best treatment choice?

See Byrne: Behavioral Strategies of CBT-I, Sleep Restriction Treatment p 35
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