ME and CFS Medical Abnormalities – Sleep Issues

 

Following is a list of articles about abnormalities in sleep in ME and CFS.

Links to the more than 1,000 peer-reviewed journal articles are listed on the ME and CFS Medical Abnormalities page of this website.

 

Castro-Marrero J, Zaragozá MC, González-Garcia S, Aliste L, Sáez-Francàs N, Romero O, Ferré A, Fernández de Sevilla T, Alegre J. Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Sleep Res. 2018 May 16:e12703. PMID: 29770505

This study aimed to assess the self-reported sleep quality and its impact on quality of life in a Spanish community-based chronic fatigue syndrome/myalgic encephalomyelitis cohort. The findings suggest that a large chronic fatigue syndrome/myalgic encephalomyelitis sample presents poor sleep quality, as assessed by the Pittsburgh Sleep Quality Index, and that this poor sleep quality is associated with many aspects of quality of life.

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Morris G, Stubbs B, Köhler CA, Walder K, Slyepchenko A, Berk M, Carvalho AF. The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis. Sleep Med Rev. 2018 Apr 4. PMID: 29759891

In this review focusing on CFS, bipolar disorder and MS as examples of neuro-immune disorders, the authors propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation.

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Orjatsalo M, Alakuijala A, Partinen M. Autonomic Nervous System Functioning Related to Nocturnal Sleep in Patients With Chronic Fatigue Syndrome Compared to Tired Controls. J Clin Sleep Med. 2018 Feb 15;14(2):163-171. PMID: 29246267

The study results suggest a nocturnal dysfunction of the cardiac autonomic nervous system in CFS, presenting as lower parasympathetic tone in deep sleep and higher sympathetic tone asleep.

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Josev EK, Jackson ML, Bei B, Trinder J, Harvey A, Clarke C, Snodgrass K, Scheinberg A, Knight SJ. Sleep Quality in Adolescents With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). J Clin Sleep Med. 2017 Sep 15;13(9):1057-1066. PMID: 28760189

This study provides objective and subjective evidence of sleep disturbance in adolescents with CFS/ME compared with healthy adolescent controls.

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Pajediene E, Bileviciute-Ljungar I, Friberg D. Sleep patterns among patients with chronic fatigue: A polysomnography-based study. Clin Respir J. 2018 Apr;12(4):1389-1397. PMID: 28752613

The purpose of this study was to detect treatable sleep disorders among patients complaining of chronic fatigue by using sleep questionnaires and polysomnography.

More than half of a group of chronic fatigue patients, who also have excessive daytime sleepiness and/or tiredness, were diagnosed with sleep disorders such as obstructive sleep apnoea, periodic limb movement disorder and/or restless legs syndrome.

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Feiring B, Laake I, Bakken IJ, Greve-Isdahl M, Wyller VB, Håberg SE, Magnus P, Trogstad L. HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway. Vaccine. 2017 Jul 24;35(33):4203-4212. PMID: 28648542

The researchers studied the association between HPV vaccination and risk of CFS/ME and also assessed medical history in relation to both risk of CFS/ME and HPV vaccine uptake. No indication of increased risk of CFS/ME following HPV vaccination was observed among girls in the first 6 birth cohorts offered HPV vaccine through the national immunisation programme in Norway.

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Pedersen M, Ekstedt M, Småstuen MC, Wyller VB, Sulheim D, Fagermoen E, Winger A, Pedersen E, Hrubos-Strøm H. Sleep-wake rhythm disturbances and perceived sleep in adolescent chronic fatigue syndrome. J Sleep Res. 2017 Oct;26(5):595-601. PMID: 28470767

The aim of this cross-sectional study was to investigate sleep-wake rhythm and perceived sleep in adolescent CFS patients compared to healthy individuals. The activity measures showed that the CFS patients stayed significantly longer in bed, had a significantly delayed mid-sleep time and a more varied sleep-wake rhythm during weekdays compared with healthy individuals. On the KSQ, the CFS patients reported significantly more insomnia symptoms, sleepiness, awakening problems and a longer sleep onset latency than healthy individuals.

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Milrad SF, Hall DL, Jutagir DR, Lattie EG, Ironson GH, Wohlgemuth W, Nunez MV, Garcia L, Czaja SJ, Perdomo DM, Fletcher MA, Klimas N, Antoni MH. Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women. J Neuroimmunol. 2017 Feb 15;303:43-50. PMID: 28038892

This study examines the relationships between sleep quality, pro-inflammatory cytokines, and CFS/ME symptoms. Poor sleep quality (PSQI global score) was associated with greater pro-inflammatory cytokine levels: interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α). Worse sleep quality related to greater fatigue severity and fatigue-related interference with daily activities, and more severe and frequent CDC-defined core CFS/ME symptoms.

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Russell C, Wearden AJ, Fairclough G, Emsley RA, Kyle SD. Subjective But Not Actigraphy-Defined Sleep Predicts Next-Day Fatigue in Chronic Fatigue Syndrome: A Prospective Daily Diary Study. Sleep. 2015 Dec 22. PMID: 26715232

The authors show that nightly subjective sleep predicts next-day fatigue in CFS and identify important factors driving this relationship.

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Snodgrass K, Harvey A, Scheinberg A, Knight S. Sleep Disturbances in Pediatric Chronic Fatigue Syndrome: A Review of Current Research. J Clin Sleep Med. 2015 Jul 15;11(7):757-64. PMID: 25766714

A meta review suggests that children and adolescents with CFS experience sleep disturbances.

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Neu D, Mairesse O, Verbanck P, Le Bon O. Slow wave sleep in the chronically fatigued: Power spectra distribution patterns in chronic fatigue syndrome and primary insomnia. Clin Neurophysiol. 2015 Oct;126(10):1926-33. PMID: 25620040

The authors found consistent evidence for lower proportions of slow oscillations during slow wave sleep in CFS patients.

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Gotts ZM, Deary V, Newton J, Van der Dussen D, De Roy P, Ellis JG. Are there sleep-specific phenotypes in patients with chronic fatigue syndrome? A cross-sectional polysomnography analysis. BMJ Open. 2013 Jun 20;3(6). PMID: 23794547

Of 343 patients with CFS, 30.3% were identified with a Primary Sleep Disorder explaining their diagnosis. Of the remaining patients, 89.1% met quantitative criteria for at least one objective sleep problem.

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Togo F, Natelson BH. Heart rate variability during sleep and subsequent sleepiness in patients with chronic fatigue syndrome. Auton Neurosci. 2013 Jun;176(1-2):85-90. PMID: 23499514

Results of this study suggest that beat-to-beat RR interval dynamics or autonomic nervous system activity during non-REM sleep might be associated with disrupted sleep in patients with CFS.

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Mariman AN, Vogelaers DP, Tobback E, Delesie LM, Hanoulle IP, Pevernagie DA. Sleep in the chronic fatigue syndrome. Sleep Med Rev. 2013 Jun;17(3):193-9. PMID:23046847

There is currently insufficient evidence to indicate that treatment of primary sleep disorders sufficiently improves the fatigue associated with CFS. Therefore, primary sleep disorders may be a comorbid rather than an exclusionary condition with respect to CFS.

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Le Bon O, Neu D, Berquin Y, Lanquart JP, Hoffmann R, Mairesse O, Armitage R. Ultra-slow delta power in chronic fatigue syndrome. Psychiatry Res. 2012 Dec 30;200(2-3):742-7. PMID: 22771174

CFS is associated with lower ultra-slow (0.5-0.8Hz) delta power, underscoring the importance of looking beyond conventional EEG frequency bands.

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Mariman A, Vogelaers D, Hanoulle I, Delesie L, Pevernagie D. Subjective sleep quality and daytime sleepiness in a large sample of patients with chronic fatigue syndrome (CFS). Acta Clin Belg. 2012 Jan-Feb;67(1):19-24. PMID: 22480034

A distinct subgroup of CFS patients with clinical features of insomnia and specific sleep problems was identified.

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Jackson ML, Bruck D. Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review. J Clin Sleep Med. 2012 Dec 15;8(6):719-28. PMID:23243408

This review provides a comprehensive overview of the literature examining sleep in CFS/ME and the issues surrounding the current research findings.

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Mariman A, Vogelaers D, Hanoulle I, Delesie L, Tobback E, Pevernagie D. Validation of the three-factor model of the PSQI in a large sample of chronic fatigue syndrome (CFS) patients. J Psychosom Res. 2012 Feb;72(2):111-3. PMID: 22281451

Sleep disturbances in CFS were evaluated according to the Pittsburgh Sleep Quality Index (PSQI) scale.

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Wu HS, Davis JE, Natavio T. Fatigue and disrupted sleep-wake patterns in patients with cancer: a shared mechanism. Clin J Oncol Nurs. 2012 Apr;16(2):E56-68. PMID: 22459538

The strong and potentially reciprocal relationship between cancer-related fatigue (CRF) and disrupted sleep-wake patterns suggests a possible shared physiologic pathway.

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Kishi A, Natelson BH, Togo F, Struzik ZR, Rapoport DM, Yamamoto Y. Sleep-Stage Dynamics in Patients with Chronic Fatigue Syndrome with or without Fibromyalgia. Sleep. 2011 Nov 1;34(11):1551-60. PMID: 22043126

The probability of transition from REM sleep to waking was significantly greater in subjects with CFS alone than in control subjects. Probabilities of (a) transitions from waking, REM sleep, and S1 to S2 and (b) those from SWS to waking and S1 were significantly greater in subjects with CFS+FM than in control subjects; in addition, rates of these transitions were also significantly increased in subjects with CFS+FM. These results suggest that CFS and FM may be different illnesses associated with different problems of sleep regulation.

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Spitzer AR, Broadman M. Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate. Pain Pract. 2010 Jan-Feb;10(1):54-9. PMID: 20629967

Abnormal findings on sleep studies and associated human leukocyte antigen markers, and a clinical pattern suggestive of narcolepsy, are present in a high proportion of CFS and fibromyalgia patients. Sixty percent of patients treated with oxybate experienced significant relief of pain, while 75% experienced significant relief of fatigue. The authors postulate that the response to oxybate in CFS and FM suggests a disturbance of sleep similar to narcolepsy.

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Kishi A, Natelson BH, Togo F, Struzik ZR, Rapoport DM, Yamamoto Y. Sleep stage transitions in chronic fatigue syndrome patients with or without fibromyalgia. Conf Proc IEEE Eng Med Biol Soc. 2010;2010:5391-4. PMID: 21096267

CFS includes specific sleep problems, including difficulties in transitioning from REM sleep to wakening.

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Neu D, Kajosch H, Peigneux P, Verbanck P, Linkowski P, Le Bon O. Cognitive impairment in fatigue and sleepiness associated conditions. Psychiatry Res. 2010 Dec 31. PMID: 21196050

CFS patients have sleep disorders that prompt cognitive and behavioural motor performance.

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Creti L, Libman E, Baltzan M, Rizzo D, Bailes S, Fichten CS. Impaired sleep in chronic fatigue syndrome: how is it best measured? J Health Psychol. 2010 May;15(4):596-607. PMID: 20460416

In CFS: (a) objectively measured nocturnal sleep time effectively approximated subjective experience although nocturnal wakefulness did not; (b) total sleep time and sleep efficiency differentiated individuals with and without insomnia complaints; (c) daytime sleepiness, fatigue, and non-refreshing sleep were not reflected by the objective sleep-related measures (polysomnography and actigraphy).

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Togo F, Natelson BH, Cherniack NS, Klapholz M, Rapoport DM, Cook DB. Sleep is not disrupted by exercise in patients with chronic fatigue syndromes. Med Sci Sports Exerc. 2010 Jan;42(1):16-22. PMID: 20010134

Sleep is disturbed in CFS patients as a group, but exercise does not exacerbate this sleep disturbance.

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Decker MJ, Tabassum H, Lin JM, Reeves WC. Electroencephalographic correlates of Chronic Fatigue Syndrome. Behav Brain Funct. 2009 Oct 6;5:43. PMID: 19807920

In persons with CFS, delta power was diminished during slow wave sleep, but elevated during both stage 1 and REM. Alpha power was reduced during stage 2, slow wave, and REM sleep. Those with CFS also had significantly lower theta, sigma, and beta spectral power during stage 2, Slow Wave Sleep, and REM.

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Libman E, Creti L, Baltzan M, Rizzo D, Fichten CS, Bailes S. Sleep apnea and psychological functioning in chronic fatigue syndrome. J Health Psychol. 2009 Nov;14(8):1251-67. PMID: 19858344

CFS participants with and without sleep apnea/hypopnea syndrome did not differ on various measures. The authors conclude that SAHS should not be an exclusion criterion for CFS.

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Neu D, Cappeliez B, Hoffmann G, Verbanck P, Linkowski P, Le Bon O. High slow-wave sleep and low-light sleep: chronic fatigue syndrome is not likely to be a primary sleep disorder. J Clin Neurophysiol. 2009 Jun;26(3):207-12. PMID: 19424087

Sleep efficiency was lower in both CFS than controls. CFS patients showed a higher microarousal index than controls. Anxiety, but not depression symptoms were more intense in the CFS group. The distribution of nonrapid eye movement sleep in CFS differs sizeably from what can be observed in a primary sleep disorder.

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Armitage R, Landis C, Hoffmann R, Lentz M, Watson N, Goldberg J, Buchwald D. Power spectral analysis of sleep EEG in twins discordant for chronic fatigue syndrome. J Psychosom Res. 2009 Jan;66(1):51-7. PMID: 19073294

No significant differences in spectral power in any frequency band in a sleep study were found between those with CFS and their nonfatigued cotwins.

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Neu D, Hoffmann G, Moutrier R, Verbanck P, Linkowski P, Le Bon O. Are patients with chronic fatigue syndrome just ‘tired’ or also ‘sleepy’? J Sleep Res. 2008 Dec;17(4):427-31. PMID: 19021860

The “fatigue” in CFS is not exactly the same as normal sleepiness.

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Togo F, Natelson BH, Cherniack NS, FitzGibbons J, Garcon C, Rapoport DM. Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia. Arthritis Res Ther. 2008;10(3):R56. PMID: 18474105

CFS patients had significant differences in polysomnographic findings from healthy controls and felt sleepier and more fatigued than controls after a night’s sleep. This difference was due primarily to a decrease in the length of periods of uninterrupted sleep in the patients with more sleepiness in the morning than on the night before.

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Kishi A, Struzik ZR, Natelson BH, Togo F, Yamamoto Y. Dynamics of sleep stage transitions in healthy humans and patients with chronic fatigue syndrome. Am J Physiol Regul Integr Comp Physiol. 2008 Jun;294(6):R1980-7. PMID: 18417644

Specific sleep problems in CFS are examined.

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Majer M, Jones JF, Unger ER, Youngblood LS, Decker MJ, Gurbaxani B, Heim C, Reeves WC. Perception versus polysomnographic assessment of sleep in CFS and non-fatigued control subjects: results from a population-based study. BMC Neurol. 2007 Dec 5;7:40. PMID: 18053240

People with CFS reported sleep problems significantly more often than control subjects. Yet, when measured these parameters and sleep architecture did not differ between the two subject groups.

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Ohinata J, Suzuki N, Araki A, Takahashi S, Fujieda K, Tanaka H. Actigraphic assessment of sleep disorders in children with chronic fatigue syndrome. Brain Dev. 2008 May;30(5):329-33. PMID: 18031961

Compared to the control group, total sleep time was longer and physical activity was lower in CFS.

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Neu D, Mairesse O, Hoffmann G, Dris A, Lambrecht LJ, Linkowski P, Verbanck P, Le Bon O. Sleep quality perception in the chronic fatigue syndrome: correlations with sleep efficiency, affective symptoms and intensity of fatigue. Neuropsychobiology. 2007;56(1):40-6. PMID: 17986836

CFS patients reported poor quality sleep, but objective sleep quality parameters, like the Sleep Efficiency Index (SEI) or the amount of slow-wave sleep did not differ significantly.

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Tajima S, Kuratsune H, Yamaguti K, Takahashi A, Takashima S, Watanabe Y, Nishizawa Y. Estimation of fatigue state in patient with CFS using actigraph and R-R interval power spectrum analysis. Nihon Rinsho. 2007 Jun;65(6):1057-64. PMID: 17561697

Actigraphy analysis showed that mean awake activity was decreased and duration of sleep was prolonged in patients with CFS.

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Kumano-go T, Adachi H, Sugita Y. Sleep disturbance in chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):1017-22. PMID: 17561691

CFS patients display a variety of sleep disorders.

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Armitage R, Landis C, Hoffmann R, Lentz M, Watson NF, Goldberg J, Buchwald D. The impact of a 4-hour sleep delay on slow wave activity in twins discordant for chronic fatigue syndrome. Sleep. 2007 May;30(5):657-62. PMID: 17552382

CFS is associated with a blunted slow wave analysis response to sleep challenge, suggesting that the basic sleep drive and homeostatic response are impaired.

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Van Hoof E, De Becker P, Lapp C, Cluydts R, De Meirleir K. Defining the occurrence and influence of alpha-delta sleep in chronic fatigue syndrome. Am J Med Sci. 2007 Feb;333(2):78-84. PMID: 17301585

CFS patients experienced a prolonged sleep latency, showed a low sleep efficiency index, and had a low percentage of slow wave sleep.

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Reeves WC, Heim C, Maloney EM, Youngblood LS, Unger ER, Decker MJ, Jones JF, Rye DB. Sleep characteristics of persons with chronic fatigue syndrome and non-fatigued controls: results from a population-based study. BMC Neurol. 2006 Nov 16;6:41. PMID: 17109739

Although disordered breathing during sleep may be associated with CFS, this study generally did not provide evidence that altered sleep architecture is a critical factor in CFS.

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Guilleminault C, Poyares D, Rosa A, Kirisoglu C, Almeida T, Lopes MC. Chronic fatigue, unrefreshing sleep and nocturnal polysomnography. Sleep Med. 2006 Sep;7(6):513-20. PMID: 16934523

The complaints of chronic fatigue and unrefreshing sleep were associated with an abnormal cyclic alternating pattern rate, with increase in slow delta power spectrum, affirming the presence of an abnormal sleep progression and non-rapid eye movement sleep instability. These specific patterns were related to subtle, undiagnosed sleep-disordered breathing.

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Unger ER, Nisenbaum R, Moldofsky H, Cesta A, Sammut C, Reyes M, Reeves WC. Sleep assessment in a population-based study of chronic fatigue syndrome. BMC Neurol. 2004 Apr 19;4:6. PMID: 15096280

Sleep issues were examined for a population of CFS patients in Wichita, Kansas. 81.4% of subjects had an abnormality in at least one SAQ sleep factor. Subjects with sleep factor abnormalities had significantly lower wellness scores but statistically unchanged fatigue severity scores compared to those without SAQ abnormality.

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Hamilos DL, Nutter D, Gershtenson J, Ikle D, Hamilos SS, Redmond DP, Di Clementi JD, Schmaling KB, Jones JF. Circadian rhythm of core body temperature in subjects with chronic fatigue syndrome. Clin Physiol. 2001 Mar;21(2):184-95. PMID: 11318826

In ambulatory conditions, the circadian rhythm of CBT in CFS is nearly indistinguishable from that of normal control subjects although there was a tendency for greater variability in the rhythm. Hence, it is unlikely that the symptoms of CFS are because of disturbance in the circadian rhythm of CBT.

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Stores G, Fry A, Crawford C. Sleep abnormalities demonstrated by home polysomnography in teenagers with chronic fatigue syndrome. J Psychosom Res. 1998 Jul;45(1 Spec No):85-91. PMID: 9720858

Compared with controls, teenagers with CFS showed significantly higher levels of sleep disruption by both brief and longer awakenings.

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Morriss RK, Wearden AJ, Battersby L. The relation of sleep difficulties to fatigue, mood and disability in chronic fatigue syndrome. J Psychosom Res. 1997 Jun;42(6):597-605. PMID: 9226607

CFS patients reported significantly more naps and waking by pain, a similar prevalence of difficulties in maintaining sleep, and significantly less difficulty getting off to sleep compared to depressed patients. Sleep continuity complaints preceded fatigue in only 20% of CFS patients, but there was a strong association between relapse and sleep disturbance. Disrupted sleep appears to complicate the course of CFS. Sleep complaints in CFS do not seem related to depression.

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Bennett AL, Mayes DM, Fagioli LR, Guerriero R, Komaroff AL. Somatomedin C (insulin-like growth factor I) levels in patients with chronic fatigue syndrome. J Psychiatr Res. 1997 Jan-Feb;31(1):91-6. PMID: 9201651

In contrast to patients with fibromyalgia, in whom levels of somatomedin C have been found to be reduced, levels in patients with CFS were found to be elevated. Thus, despite the clinical similarities between these two conditions, they may be associated with different abnormalities of sleep and/or of the somatotropic neuroendocrine axis.

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Fischler B, Le Bon O, Hoffmann G, Cluydts R, Kaufman L, De Meirleir K. Sleep anomalies in the chronic fatigue syndrome. A comorbidity study. Neuropsychobiology. 1997;35(3):115-22. PMID: 9170115

CFS sufferers were different than controls on variables of sleep-onset latency and the number of stage shifts/hour.

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Williams G, Pirmohamed J, Minors D, Waterhouse J, Buchan I, Arendt J, Edwards RH. Dissociation of body-temperature and melatonin secretion circadian rhythms in patients with chronic fatigue syndrome. Clin Physiol. 1996 Jul;16(4):327-37. PMID: 8842569

CFS patients showed no significant correlation between the timing of the temperature acrophase and the melatonin onset, whereas the normal significant correlation was observed in the controls. Dissociation of circadian rhythms could be due to the sleep deprivation and social disruption, and/or the reduction in physical activity which typically accompany CFS.

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Schaefer KM. Sleep disturbances and fatigue in women with fibromyalgia and chronic fatigue syndrome. J Obstet Gynecol Neonatal Nurs. 1995 Mar-Apr;24(3):229-33. PMID: 7782955

Women with CFS encounter problems with quality as well as amount of sleep.

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Manu P, Lane TJ, Matthews DA, Castriotta RJ, Watson RK, Abeles M. Alpha-delta sleep in patients with a chief complaint of chronic fatigue. South Med J. 1994 Apr;87(4):465-70. PMID: 8153772

Alpha-delta sleep is not a marker of CFS, but may contribute to the illness of nondepressed patients with these conditions.

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Buchwald D, Pascualy R, Bombardier C, Kith P. Sleep disorders in patients with chronic fatigue. Clin Infect Dis. 1994 Jan;18 Suppl 1:S68-72. PMID: 8148456

Study results suggest that patients who qualify for CFS diagnoses may have sleep disorders that, while they don’t cause the disease, may improve with treatment.

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Krupp LB, Jandorf L, Coyle PK, Mendelson WB. Sleep disturbance in chronic fatigue syndrome. J Psychosom Res. 1993 May;37(4):325-31. PMID: 8510058

Subjective sleep disturbance is common in CFS and some CFS patients may have objective sleep disorders.

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Morriss R, Sharpe M, Sharpley AL, Cowen PJ, Hawton K, Morris J. Abnormalities of sleep in patients with the chronic fatigue syndrome. BMJ. 1993 May 1;360(6886):1161-4. PMID: 8499816

Most people in a group of CFS patients had sleep disorders, which are likely to contribute to daytime fatigue.

 

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