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ME/CFS Atlas — A public knowledge atlas for ME/CFS

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ME/CFS Atlas is an evidence reference platform, not a medical provider. Content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

Evidence browser

Search and filter 6,205 studies by evidence level, diagnostic criteria, PEM status, and research domain. Each entry links to the original source.

Studies sorted by evidence level, then year. Browse by topic instead →

Evidence level (E0–E3) reflects study type and replication, not methodological quality. A weak systematic review still sits at E0. How evidence levels work →

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280 studies

E0 — Consensus654E1 — Replicated321E2 — Moderate2,807E3 — Preliminary2,423

ME/CFS4,040Long COVID224Post-infectious190Overlapping1,064

Required for diagnosis417Not specified / unclear2,251Not required3,537

Post-Exertional Malaise1,082Cognitive Dysfunction1,749Pain1,628Unrefreshing Sleep805Orthostatic Intolerance484

Cytokines821Gene Expression573Metabolomics477Neuroimaging472Autoantibodies460

Infection-Triggered1,182Long COVID Overlap604Pediatric496Severe232

Strong Phenotyping445Sex-Stratified330Severe ME Included119

Systematic Review272Meta-Analysis61RCT301

Peer-reviewed6,148Preprint3Unclear54

161–180 of 280 studies

E2 ModerateBehavioralPEM not requiredLongitudinal

Predictors of persistent and new-onset fatigue in adolescent girls.

ter Wolbeek, Maike, van Doornen, Lorenz J P, Kavelaars, Annemieke et al.·Pediatrics·2008

This study followed 653 teenage girls over one year to understand why some develop long-lasting fatigue while others recover. Researchers found that about 26% of girls who were severely fatigued at the start remained fatigued throughout the year. Depression, anxiety, low physical activity, and poor sleep were linked to persistent or new fatigue, suggesting that emotional health and lifestyle habits play important roles in fatigue development.

E2 ModerateCohortPEM not requiredCross-Sectional

Are patients with chronic fatigue syndrome just 'tired' or also 'sleepy'?

Neu, Daniel, Hoffmann, Guy, Moutrier, Robert et al.·Journal of sleep research·2008

This study asked whether ME/CFS patients experience daytime sleepiness (like wanting to nap) or mainly fatigue (exhaustion that doesn't improve with rest). Researchers tested 16 ME/CFS patients, 13 sleep apnea patients, and 12 healthy people using both objective sleep tests and questionnaires. They found that ME/CFS patients reported much higher fatigue than sleepiness, while sleep apnea patients showed the opposite pattern—suggesting fatigue and sleepiness are different problems.

E2 ModerateCohortPEM not requiredCross-Sectional

Perception versus polysomnographic assessment of sleep in CFS and non-fatigued control subjects: results from a population-based study.

Majer, Matthias, Jones, James F, Unger, Elizabeth R et al.·BMC neurology·2007

People with ME/CFS commonly report that their sleep doesn't feel refreshing and that they have trouble sleeping, even though standard sleep tests don't always show obvious sleep problems. This study compared how 35 people with ME/CFS and 40 healthy people described their sleep quality against what their actual sleep looked like on overnight sleep monitoring. Interestingly, the sleep recordings looked similar between both groups, but ME/CFS patients were more accurate at noticing their actual sleep behavior, while healthy controls tended to overestimate how long it took them to fall asleep.

E2 ModerateCohortPEM not requiredCross-Sectional

Sleep quality perception in the chronic fatigue syndrome: correlations with sleep efficiency, affective symptoms and intensity of fatigue.

Neu, Daniel, Mairesse, Olivier, Hoffmann, Guy et al.·Neuropsychobiology·2007

ME/CFS patients often report feeling like they have poor sleep quality, even though doctors cannot always find obvious problems when measuring sleep objectively. This study compared how ME/CFS patients and healthy people rated their own sleep quality and found that ME/CFS patients consistently reported worse sleep, despite having similar sleep efficiency measurements. The poor sleep quality perception was somewhat linked to fatigue severity but not related to depression or anxiety symptoms.

E2 ModerateCohortPEM not requiredCross-Sectional

[Estimation of fatigue state in patient with CFS using actigraph and R-R interval power spectrum analysis].

Tajima, Seiki, Kuratsune, Hirohiko, Yamaguti, Kouzi et al.·Nihon rinsho. Japanese journal of clinical medicine·2007

This study measured activity levels and sleep patterns in people with ME/CFS using wearable devices and heart rate analysis. Researchers found that ME/CFS patients had lower activity during waking hours, slept longer, experienced more frequent sleep disruptions, and showed abnormal nervous system activity during sleep compared to healthy people.

SleepAutonomic Nervous System

E2 ModerateCohortPEM not requiredCase-Control

Higher heart rate and reduced heart rate variability persist during sleep in chronic fatigue syndrome: a population-based study.

Boneva, Roumiana S, Decker, Michael J, Maloney, Elizabeth M et al.·Autonomic neuroscience : basic & clinical·2007

This study found that people with ME/CFS have a faster heart rate and less heart rate variability (natural changes in heartbeat speed) during sleep compared to healthy people. These differences suggest that the nervous system in ME/CFS patients stays more activated even during sleep, which may be related to chemical imbalances in the body.

SleepAutonomic Nervous System

E2 ModerateCohortPEM unclearCross-Sectional

An empirical delineation of the heterogeneity of chronic unexplained fatigue in women.

Vollmer-Conna, Uté, Aslakson, Eric, White, Peter D·Pharmacogenomics·2006

This study looked at 159 women to understand why chronic fatigue affects people differently. Researchers used statistical analysis to group the women into distinct clusters based on their symptoms, sleep patterns, hormone levels, and stress responses. They found that chronic fatigue is not one single condition, but rather several different conditions with different underlying causes—some linked to sleep problems, others to depression, obesity, or hormonal changes.

E2 ModerateBehavioralPEM not requiredCross-Sectional

Severe fatigue in adolescents: a common phenomenon?

ter Wolbeek, Maike, van Doornen, Lorenz J P, Kavelaars, Annemieke et al.·Pediatrics·2006

This study looked at how common severe tiredness is in teenagers and whether it's connected to depression, anxiety, and other symptoms seen in ME/CFS patients. Researchers surveyed over 3,400 teenagers about their fatigue, mood, sleep, and daily habits. They found that severe fatigue is quite common in adolescents—especially in girls—and that it often clusters with depression, anxiety, and ME/CFS-like symptoms.

E2 ModerateCohortPEM not requiredCase-Control

Sleep characteristics of persons with chronic fatigue syndrome and non-fatigued controls: results from a population-based study.

Reeves, William C, Heim, Christine, Maloney, Elizabeth M et al.·BMC neurology·2006

This study compared sleep patterns in people with ME/CFS and healthy controls using overnight sleep monitoring tests. Researchers found that people with ME/CFS had slightly more breathing interruptions during sleep, but overall sleep architecture (the normal stages and patterns of sleep) was similar between the two groups. The results suggest that while sleep problems are common in ME/CFS, they may not be caused by the same underlying sleep abnormalities seen in other sleep disorders.

E2 ModerateCohortPEM not requiredCross-Sectional

Linear data mining the Wichita clinical matrix suggests sleep and allostatic load involvement in chronic fatigue syndrome.

Gurbaxani, Brian M, Jones, James F, Goertzel, Benjamin N et al.·Pharmacogenomics·2006

Researchers analyzed clinical data from 164 ME/CFS patients and controls to identify patterns that distinguish the condition from health. Using mathematical techniques to find which body measurements best separated the two groups, they found that sleep problems and markers of physical stress (allostatic load) were important—though no single measurement was strongly predictive on its own. The study suggests that ME/CFS may involve multiple interconnected biological changes rather than one simple cause.

E2 ModerateCohortPEM not requiredCross-Sectional

Chronic fatigue syndrome impairs circadian rhythm of activity level.

Tryon, Warren W, Jason, Lenny, Frankenberry, Erin et al.·Physiology & behavior·2004

This study looked at how people with ME/CFS move and rest throughout the day and night by using activity monitors worn on the waist. Researchers found that people with ME/CFS were less active during the day and had less predictable patterns of activity and rest compared to healthy people. These disrupted patterns may help explain why ME/CFS patients experience fatigue and other symptoms.

E2 ModerateCohortPEM not requiredCase-Control

Subjective and objective sleepiness in monozygotic twins discordant for chronic fatigue syndrome.

Watson, Nathaniel F, Jacobsen, Clemma, Goldberg, Jack et al.·Sleep·2004

This study compared sleepiness in identical twins where one had ME/CFS and one did not. People with ME/CFS reported feeling much more sleepy on questionnaires, but when researchers measured how quickly they fell asleep in a lab test, both groups fell asleep at similar speeds. The researchers suggest that people with ME/CFS may be confusing their chronic exhaustion with sleepiness.

E2 ModerateCohortPEM not requiredCross-Sectional

Sleep assessment in a population-based study of chronic fatigue syndrome.

Unger, Elizabeth R, Nisenbaum, Rosane, Moldofsky, Harvey et al.·BMC neurology·2004

This study looked at sleep problems in 339 people with ME/CFS from Kansas to understand how sleep issues relate to their fatigue. Researchers found that over 80% of ME/CFS patients had at least one sleep problem, with non-restorative sleep (sleep that doesn't feel refreshing) and restlessness being the most common. Interestingly, ME/CFS patients were not unusually sleepy during the day, which suggests their fatigue comes from a different mechanism than typical sleep deprivation.

E2 ModerateCohortPEM not requiredCross-Sectional

Sleep and chronic pain: challenges to the alpha-EEG sleep pattern as a pain specific sleep anomaly.

Rains, Jeanetta C, Penzien, Donald B·Journal of psychosomatic research·2003

Researchers looked at a brain wave pattern during sleep called alpha-EEG, which has been thought to be linked to chronic pain conditions like fibromyalgia and ME/CFS. They found that this sleep pattern was uncommon (only 5% of patients) and occurred in people with chronic pain, psychiatric conditions, and other medical problems. Surprisingly, less than 40% of people with this sleep pattern actually had chronic pain, suggesting the pattern alone does not cause pain.

E2 ModerateCohortPEM not requiredCase-Control

Comparison of subjective and objective measures of insomnia in monozygotic twins discordant for chronic fatigue syndrome.

Watson, Nathaniel F, Kapur, Vishesh, Arguelles, Lester M et al.·Sleep·2003

People with ME/CFS report feeling like they sleep poorly and don't rest well, but when researchers measured their actual sleep using medical equipment, the sleep looked similar to their healthy identical twins. The main difference was that people with ME/CFS had more REM sleep (a specific sleep stage) and felt much less refreshed after sleeping, even though the equipment showed they were sleeping normally. This suggests that ME/CFS may involve a mismatch between how sleep actually is and how it feels.

E2 ModerateCohortPEM not requiredCase-Control

Health and functional status of twins with chronic regional and widespread pain.

Aaron, Leslie A, Arguelles, Lester M, Ashton, Suzanne et al.·The Journal of rheumatology·2002

This study looked at twins where one had chronic pain (either in one area or widespread) and the other did not, to understand how pain affects health and function independent of ME/CFS. Researchers found that chronic pain significantly worsens general health perception, physical functioning, and sleep quality, effects that remain even after accounting for ME/CFS. However, the mental health impact of pain appears closely linked to having ME/CFS symptoms together.

Pain and SensitizationSleep

E2 ModerateBehavioralPEM not requiredCross-Sectional

Fatigue after breast cancer and in chronic fatigue syndrome: similarities and differences.

Servaes, Petra, Prins, Judith, Verhagen, Stans et al.·Journal of psychosomatic research·2002

This study compared 57 women with ME/CFS to 57 women who had breast cancer and were experiencing severe fatigue after treatment. Researchers measured fatigue, physical activity, mood, sleep, and concentration using questionnaires, tests, and activity monitors worn for 12 days. While both groups experienced significant fatigue, ME/CFS patients generally had more severe symptoms overall, though some breast cancer survivors reported similar problems with sleep and concentration.

SleepCognitive Impairment

E2 ModerateCohortPEM not requiredCross-Sectional

Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder.

Aaron, L A, Burke, M M, Buchwald, D·Archives of internal medicine·2000

This study found that ME/CFS, fibromyalgia, and temporomandibular disorder (TMD) often occur together in the same patients and share similar symptoms like pain, fatigue, and sleep problems. The researchers also discovered that patients with these conditions frequently experience other illnesses like irritable bowel syndrome and headaches—much more often than healthy people do. The study suggests these conditions may be connected in some way we don't yet fully understand.

Pain and SensitizationSleepCognitive Impairment

E2 ModerateCohortPEM not requiredCross-Sectional

How significant are primary sleep disorders and sleepiness in the chronic fatigue syndrome?

Le Bon, O, Fischler, B, Hoffmann, G et al.·Sleep research online : SRO·2000

This study looked at whether sleep problems might explain ME/CFS symptoms in 46 patients. Researchers found that many CFS patients did have sleep disorders like sleep apnea, but these sleep problems were not connected to how severe their CFS was or their other symptoms. Importantly, over half of the CFS patients had no sleep disorders at all, suggesting that ME/CFS is a distinct condition separate from typical sleep problems.

E2 ModerateCohortPEM not requiredCross-Sectional

High nocturnal melatonin in adolescents with chronic fatigue syndrome.

Knook, L, Kavelaars, A, Sinnema, G et al.·The Journal of clinical endocrinology and metabolism·2000

Researchers measured melatonin (a natural hormone that helps control sleep) in saliva samples from 13 teenagers with ME/CFS and 15 healthy teenagers. They found that ME/CFS patients had significantly higher melatonin levels during the night, yet paradoxically, all the ME/CFS patients reported their sleep felt unrefreshing and unrestorative. Based on this finding, the researchers suggested that giving melatonin supplements to teenagers with ME/CFS may not be helpful.

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PEM Immune Neuro Metabolic Biomarkers Severe ME Long COVID Cognitive

Curated Collections

Thematic groupings by clinical question or research area.

Neuroinflammation Evidence

PET imaging and other studies providing evidence for brain inflammation in ME/CFS.

Metabolism & Mitochondria

Metabolomics and mitochondrial function studies revealing energy metabolism disruption.

Biomarkers

Studies identifying potential biological markers for ME/CFS diagnosis and stratification.

PEM-Specific Research

Studies specifically examining post-exertional malaise, the hallmark symptom of ME/CFS.