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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 6,119 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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266 studies

E0 — Consensus628E1 — Replicated319E2 — Moderate2,756E3 — Preliminary2,416

ME/CFS4,009Long COVID207Post-infectious188Overlapping1,031

Required for diagnosis409Not specified / unclear2,190Not required3,520

Post-Exertional Malaise1,039Cognitive Dysfunction1,711Pain1,606Unrefreshing Sleep786Orthostatic Intolerance470

Cytokines812Gene Expression564Metabolomics469Neuroimaging464Autoantibodies454

Infection-Triggered1,157Long COVID Overlap563Pediatric494Severe227

Strong Phenotyping427Sex-Stratified325Severe ME Included115

Systematic Review256Meta-Analysis59RCT299

Peer-reviewed6,062Preprint3Unclear54

141–160 of 266 studies

E2 ModerateCohortPEM not requiredCross-Sectional

High slow-wave sleep and low-light sleep: chronic fatigue syndrome is not likely to be a primary sleep disorder.

Neu, Daniel, Cappeliez, Bernard, Hoffmann, Guy et al.·Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society·2009

This study compared sleep patterns between people with ME/CFS and people with a primary sleep disorder (sleep apnea) to see if ME/CFS might actually be a sleep problem in disguise. Researchers found that ME/CFS patients have distinctly different sleep patterns—more deep sleep and fewer light sleep stages—compared to people with actual sleep disorders. This suggests ME/CFS is not primarily a sleep disorder, even though both conditions cause people to feel unrefreshed.

E2 ModerateCohortPEM not requiredCross-Sectional

Replication of an empirical approach to delineate the heterogeneity of chronic unexplained fatigue.

Aslakson, Eric, Vollmer-Conna, Uté, Reeves, William C et al.·Population health metrics·2009

This study looked at nearly 400 women from different parts of Georgia to understand why chronic fatigue affects people so differently. Instead of treating all chronic fatigue as one disease, researchers found that people fall into five distinct groups with different symptom patterns—some with sleep and mood problems, some with weight and metabolic issues, and some without significant fatigue at all. The findings suggest that chronic fatigue is not one-size-fits-all, and doctors may need personalized approaches for different patient groups.

E2 ModerateCohortPEM not requiredCross-Sectional

Electroencephalographic correlates of Chronic Fatigue Syndrome.

Decker, Michael J, Tabassum, Humyra, Lin, Jin-Mann S et al.·Behavioral and brain functions : BBF·2009

This study looked at brain wave patterns during sleep in people with ME/CFS compared to healthy controls using a sleep study test. Researchers found that people with ME/CFS had abnormal brain wave activity during different sleep stages, particularly weaker delta waves during deep sleep and weaker alpha waves during REM sleep. These findings suggest that the problem in ME/CFS may not be the structure of sleep itself, but rather how the brain regulates and maintains restorative sleep.

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

Actigraphic assessment of sleep disorders in children with chronic fatigue syndrome.

Ohinata, Junko, Suzuki, Nao, Araki, Akiko et al.·Brain & development·2008

This study examined sleep patterns in 12 children with ME/CFS using a special watch-like device called an actigraph that tracks movement and sleep. Children with ME/CFS slept much longer than healthy children but had lower activity levels and disrupted sleep patterns. The researchers found two main types of sleep problems: some children had very irregular sleep schedules, while others had a delayed sleep phase (sleeping much later than normal).

E2 ModerateCohortPEM not requiredCross-Sectional

Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia.

Togo, Fumiharu, Natelson, Benjamin H, Cherniack, Neil S et al.·Arthritis research & therapy·2008

This study looked at sleep patterns in people with ME/CFS, comparing those with and without fibromyalgia to healthy people. Researchers found that ME/CFS patients had worse sleep quality and felt more tired and sleepy after sleeping than healthy controls. The key finding was that some ME/CFS patients experienced frequent sleep interruptions—their sleep kept getting broken up—which made their sleep feel unrefreshing even though they didn't have diagnosable sleep disorders like sleep apnea.

E2 ModerateCohortPEM not requiredCross-Sectional

Dynamics of sleep stage transitions in healthy humans and patients with chronic fatigue syndrome.

Kishi, Akifumi, Struzik, Zbigniew R, Natelson, Benjamin H et al.·American journal of physiology. Regulatory, integrative and comparative physiology·2008

This study examined sleep patterns in people with ME/CFS compared to healthy people by recording brain activity during sleep. Researchers found that people with ME/CFS have disrupted transitions between different types of sleep, particularly trouble maintaining lighter sleep and REM sleep, and instead wake up more frequently. This suggests that the brain's sleep regulation mechanisms work differently in ME/CFS.

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

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

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 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.

Autonomic Nervous SystemSleep

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 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 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 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 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 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.

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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.