Sleeplessness and Circadian Rhythm Disorder
- Author: Mary E Cataletto, MD; Chief Editor: Selim R Benbadis, MD more...
Background
Circadian rhythm describes the approximately 24-hour cycles that are generated by an organism. Most physiological systems demonstrate circadian variations. The systems with the most prominent variations are the sleep-wake cycle, thermoregulation, and the endocrine system. Circadian rhythm disturbances can be categorized into 2 main groups: transient disorders (eg, jet lag; changed sleep schedule due to work, social responsibilities, illness) and chronic disorders. The most common chronic disorders are delayed sleep-phase syndrome (DSPS), advanced sleep-phase syndrome (ASPS), and irregular sleep-wake cycle. Katzenberg et al suggested genetic correlation (ie, clock polymorphisms) to circadian rhythm patterns.[1]
Important terms are defined as follows:
- Circadian rhythm (from circa, meaning "about" and dies, meaning day) - Approximately 24-hour cycles endogenously generated by an organism (eg, sleep-wake cycle)
- Ultradian rhythm - Biological rhythms shorter than a 24-hour cycle (eg, sleep stages)
- Entrainment - Synchronization of the circadian rhythms with environmental cues
- Free-running clock - Persistence of circadian rhythms in the absence of environmental cues (eg in patients with impaired ability to entrain or in those without time cues)
- Zeitgeber (time giver) - Specific environmental variables that provide time cues (eg, light, food-availability cycles)
- Sleeplessness (insomnia) - Difficulty initiating or maintaining sleep
- Circadian rhythm disorders - Malfunction of the circadian timing system or the biological clock
DSPS is characterized by a persistent inability (>6 mo) to fall asleep and awaken at socially accepted times. Once asleep, these patients are able to maintain their sleep and have normal total sleep times. In contrast, patients with insomnia have a lower than normal total sleep time due to difficulties in initiating or maintaining sleep.
ASPS is characterized by persistent, early evening sleep onset (between 6:00 pm and 9:00 pm), with an early morning wake-up time, generally between 3:00 am and 5:00 am. ASPS is less common than DSPS and most frequently occurs in elderly patients and in individuals who are depressed.
An irregular sleep-wake schedule features multiple sleep episodes without evidence of recognizable ultradian or circadian features of sleep and wakefulness. As with ASPS and DSPS, total sleep time is normal. Daily sleep logs demonstrate irregularity not only of sleep but also of daytime activities, including eating.
Pathophysiology
The neural basis of the circadian rhythm, the suprachiasmatic nuclei (SCN), is located in the anterior ventral hypothalamus and has been identified as the substrate that generates circadian activity. SCN lesions produce loss of circadian rhythmicity of the sleep-wake cycle, the activity-rest cycle, skin temperature, and corticosteroid secretion. Other pacemakers that are not located in the SCN are observed. For instance, core body temperature rhythm persists despite bilateral ablation of SCN. Furthermore, free-running studies have provided evidence for multiple circadian oscillators. Under free-running conditions, circadian rhythm may split into independent components.
Epidemiology
Frequency
United States
DSPS is common. Approximately 7-10% of patients who complain of insomnia are diagnosed with a circadian rhythm disorder, most often DSPS. The prevalence of DSPS is probably higher than that because the total sleep time is typically normal in patients with DSPS and because patients with DSPS adjust their lifestyle to accommodate their sleep schedule and do not seek medical treatment. In adolescence, the prevalence is approximately 7%.
True ASPS is probably quite rare. However, an age-related phase advance is common in elderly patients because they tend to go to sleep early and get up early.
The prevalence of irregular sleep-wake schedules has not been established but is said to be quite high. Irregular sleep-wake schedule is common in patients with Alzheimer disease.
Approximately 20% of US workers perform shift work; not all of these works develop shift work syndrome, and individual phase tolerance is observed.
International
Dagan et al reported the characteristics of 322 Israeli patients with circadian rhythm disorder.[2] Most patients (85%) with circadian rhythm disorder who seek medical help have DSPS. About 90% of patients with DSPS in the study by Dagan et al reported onset of DSPS in early childhood or adolescence. A cross-sectional nationwide epidemiologic study in Norway established an overall prevalence of DSPS to be 0.17% when strict International Classification of Sleep Disorders (ICSD) criteria were used.[3]
Mortality/Morbidity
The mortality rates associated with circadian rhythms are difficult to assess. Many deaths related to circadian rhythm disorders are the result of impaired performance secondary to sleep deprivation; therefore, many times, the deaths are categorized into different headings (eg, motor vehicle accidents, heavy machinery accidents, other accidents). Sometimes, deaths are sequelae of the use of hypnotics, alcohol, or both to treat insomnia.
- Shift workers have been found to have a 40% greater cardiovascular disease risk than nonshift workers. Frequency of GI symptoms, other psychosomatic symptoms, and psychiatric symptoms is also increased in shift workers.
- Daytime sleepiness in students with DSPS has been correlated with negative mood and increased smoking and alcohol consumption.
- Some of the features of depressive disorders, such as early morning awakening and decreased rapid eye movement (REM) latency, are suggestive of ASPS. Whether these changes are secondary to depression or actually cause it has not been established.
Race
Race has been associated with variations in incidence of obstructive sleep apnea (OSA); however, many variables may be associated with these differences, and further research is necessary to evaluate this.
Sex
The sex difference in circadian rhythm disorders seems to be age related.
- In children and adolescents, no significant prevalence based on sex is observed.
- In patients aged 20-40 years, little to no difference in prevalence based on sex is observed.
- In those older than 40 years, women are 1.3 times more likely to report insomnia than men.
Age
- Circadian rhythm cycles undergo changes during puberty, as do other physiologic systems. At this time, increased daytime sleepiness is seen along with the development of sleep-phase delay. Early school start times at this critically important developmental phase can be associated with symptoms of daytime sleepiness, poor concentration, and impaired performance.
- DSPS is the most common circadian rhythm disorder in children and adolescents. ASPS is more likely to appear in elderly individuals.
- Health risks associated with shift work, such as GI and psychosomatic symptoms, increase with age.
- Irregular sleep-wake rhythms can be seen in patients with neurological impairment, including those with dementia.
Katzenberg D, Young T, Finn L, et al. A CLOCK polymorphism associated with human diurnal preference. Sleep. Sep 15 1998;21(6):569-76. [Medline].
Dagan Y, Eisenstein M. Circadian rhythm sleep disorders: toward a more precise definition and diagnosis. Chronobiol Int. Mar 1999;16(2):213-22. [Medline].
Schrader H, Bovim G, Sand T. The prevalence of delayed and advanced sleep phase syndromes. J Sleep Res. Mar 1993;2(1):51-55. [Medline].
Johnson EO, Roehrs T, Roth T, Breslau N. Epidemiology of alcohol and medication as aids to sleep in early adulthood. Sleep. Mar 15 1998;21(2):178-86. [Medline].
Rosen GM, Shor AC, Geller TJ. Sleep in children with cancer. Curr Opin Pediatr. Dec 2008;20(6):676-81. [Medline].
Ming X, Walters AS. Autism spectrum disorders, attention deficit/hyperactivity disorder, and sleep disorders. Curr Opin Pulm Med. Aug 26 2009;[Medline].
Morgenthaler TI, Lee-Chiong T, Alessi C, Friedman L, Aurora RN, Boehlecke B. Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report. Sleep. Nov 1 2007;30(11):1445-59. [Medline].
Cochrane Review [book on CD-ROM]. Oxford: Cochrane; 2001. Herxheimer A, Petrie KJ.
Allen R. Development of the human circadian cycle. In: Loughlin G, et al, eds. Sleep and Breathing in Children. 2000:313-32.
Ancoli-Israel S, Klauber MR, Jones DW, et al. Variations in circadian rhythms of activity, sleep, and light exposure related to dementia in nursing-home patients. Sleep. Jan 1997;20(1):18-23. [Medline].
Boggild H, Suadicani P, Hein HO, et al. Shift work, social class, and ischaemic heart disease in middle aged and elderly men; a 22 year follow up in the Copenhagen Male Study. Occup Environ Med. Sep 1999;56(9):640-5. [Medline].
Chesson AL Jr, Littner M, Davila D, et al. Practice parameters for the use of light therapy in the treatment of sleep disorders. Standards of Practice Committee, American Academy of Sleep Medicine. Sleep. Aug 1 1999;22(5):641-60. [Medline].
Chesson AL, Anderson WM, Littner M, et al. Practice parameters for the nonpharmacologic treatment of chronic insomnia. An American Academy of Sleep Medicine report. Standards of Practice Committee of the American Academy of Sleep Medicine. Sleep. Dec 15 1999;22(8):1128-33. [Medline].
Epstein R, Chillag N, Lavie P. Starting times of school: effects on daytime functioning of fifth-grade children in Israel. Sleep. May 1 1998;21(3):250-6. [Medline].
Glaze DG. Childhood insomnia: why Chris can't sleep. Pediatr Clin North Am. Feb 2004;51(1):33-50, vi. [Medline].
Hauri PJ. Insomnia. Clin Chest Med. Mar 1998;19(1):157-68. [Medline].
Morin C, ed. Insomnia: Psychological Assessment and Management. New York, NY: Guilford Press; 1993.
Manni R, Ratti MT, Tartara A. Nocturnal eating: prevalence and features in 120 insomniac referrals. Sleep. Sep 1997;20(9):734-8. [Medline].
Martin SK, Eastman CI. Medium-intensity light produces circadian rhythm adaptation to simulated night-shift work. Sleep. Mar 15 1998;21(2):154-65. [Medline].
Meltzer LJ, Mindell JA. Nonpharmacologic treatments for pediatric sleeplessness. Pediatr Clin North Am. Feb 2004;51(1):135-51. [Medline].
Mulrooney DA, Ness KK, Neglia JP, Whitton JA, Green DM, Zeltzer LK. Fatigue and sleep disturbance in adult survivors of childhood cancer: a report from the childhood cancer survivor study (CCSS). Sleep. Feb 1 2008;31(2):271-81. [Medline].
Natale D, Sabrine W. Melatonin. Clin Tox Rev. 1997;20 (1).
Roehrs T, Roth T. Chronic insomnias associated with circadian rhythm disorders. In: Kryger M, Roth T, Dement W, eds. Principles and Practice of Sleep Medicine. 2nd ed. Philadelphia, PA: WB Saunders; 1994.
Vgontzas AN, Bixler EO, Lin HM, et al. Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. J Clin Endocrinol Metab. Aug 2001;86(8):3787-94. [Medline].
Walsh JK, Engelhardt CL. The direct economic costs of insomnia in the United States for 1995. Sleep. May 1 1999;22 Suppl 2:S386-93. [Medline].
Yazaki M, Shirakawa S, Okawa M, et al. Demography of sleep disturbances associated with circadian rhythm disorders in Japan. Psychiatry Clin Neurosci. Apr 1999;53(2):267-8. [Medline].
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