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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

161–180 of 266 studies

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 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.

Cognitive ImpairmentSleep

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 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

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

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.

E2 ModerateCohortPEM not requiredCross-Sectional

Melatonin levels in women with fibromyalgia and chronic fatigue syndrome.

Korszun, A, Sackett-Lundeen, L, Papadopoulos, E et al.·The Journal of rheumatology·1999

This study looked at melatonin—a hormone that helps control sleep and daily rhythms—in women with fibromyalgia and chronic fatigue syndrome. Researchers collected blood samples every 10 minutes over 24 hours and found that women with fibromyalgia had higher melatonin levels at night compared to healthy controls, but women with chronic fatigue syndrome did not. The authors concluded there is no evidence that taking melatonin supplements would help these patients.

E2 ModerateCohortPEM unclearLongitudinal

Prognostic factors for persons with idiopathic chronic fatigue.

Hartz, A J, Kuhn, E M, Bentler, S E et al.·Archives of family medicine·1999

This study followed 199 people with chronic fatigue for 2 years to understand which factors predicted who would improve. Researchers found that people who had clearer thinking, fewer additional symptoms, better sleep patterns, and were married tended to show the most improvement in fatigue. Interestingly, when patients improved in other symptoms like depression, muscle pain, or sleep problems, their fatigue also tended to improve together.

Cognitive ImpairmentSleep

E2 ModerateBehavioralPEM not requiredCross-Sectional

Chronic fatigue syndrome and seasonal affective disorder: comorbidity, diagnostic overlap, and implications for treatment.

Terman, M, Levine, S M, Terman, J S et al.·The American journal of medicine·1998

This study looked at whether ME/CFS symptoms get worse during winter months, similar to seasonal depression. Researchers asked 110 ME/CFS patients about their symptoms in summer and winter, and found that about one-third showed a seasonal pattern with winter worsening. This suggests that some ME/CFS patients might benefit from light therapy, a treatment commonly used for seasonal depression.

E2 ModerateCohortPEM not requiredCross-Sectional

Exploring the validity of the Chalder Fatigue scale in chronic fatigue syndrome.

Morriss, R K, Wearden, A J, Mullis, R·Journal of psychosomatic research·1998

This study tested whether the Chalder Fatigue Scale—a common questionnaire used to measure tiredness in ME/CFS patients—actually measures what it claims to measure. Researchers analyzed responses from 136 ME/CFS patients and found that fatigue has four distinct components: mental tiredness (linked to thinking problems), sleep difficulties, physical weakness (linked to low fitness), and depression. The results suggest the 11-item version of the scale works better than the original 14-item version for measuring fatigue in ME/CFS.

Cognitive ImpairmentSleep

E2 ModerateCohortPEM not requiredCross-Sectional

Sleep abnormalities demonstrated by home polysomnography in teenagers with chronic fatigue syndrome.

Stores, G, Fry, A, Crawford, C·Journal of psychosomatic research·1998

Researchers used home sleep monitoring equipment to measure sleep quality in 18 teenagers with ME/CFS compared to healthy teens of the same age and gender. They found that teenagers with ME/CFS woke up much more frequently during the night—both for brief moments and longer periods—compared to the healthy group. These frequent sleep disruptions could help explain why young people with ME/CFS feel so exhausted during the day.

E2 ModerateCohortPEM not requiredCross-Sectional

Lack of seasonal variation of symptoms in patients with chronic fatigue syndrome.

García-Borreguero, D, Dale, J K, Rosenthal, N E et al.·Psychiatry research·1998

Many people experience changes in energy, mood, appetite, and sleep across different seasons, often feeling worse in winter. This study tested whether ME/CFS patients experience these same seasonal changes. The researchers found that ME/CFS patients actually show much less seasonal variation in their symptoms compared to healthy people, suggesting their fatigue and other symptoms stay relatively constant year-round rather than fluctuating with the seasons.

E2 ModerateBehavioralPEM not requiredCross-Sectional

Correlations among Epworth Sleepiness Scale scores, multiple sleep latency tests and psychological symptoms.

Olson, L G, Cole, M F, Ambrogetti, A·Journal of sleep research·1998

This study looked at whether a simple questionnaire about daytime sleepiness (the Epworth Sleepiness Scale) actually measures the same thing as a more complex sleep test that measures how quickly people fall asleep. The researchers found that these two tests don't measure the same thing—the questionnaire is influenced by mood and psychological symptoms, while the objective sleep test is not.

E2 ModerateCohortPEM unclearCase-Control

Somatomedin C (insulin-like growth factor I) levels in patients with chronic fatigue syndrome.

Bennett, A L, Mayes, D M, Fagioli, L R et al.·Journal of psychiatric research·1997

Researchers measured levels of somatomedin C (a growth-related hormone) in 49 ME/CFS patients and compared them to 30 healthy people. They found that ME/CFS patients had higher levels of this hormone than healthy controls. This is interesting because a similar condition called fibromyalgia shows the opposite pattern—lower levels of this hormone.

E2 ModerateBehavioralPEM not requiredCross-Sectional

The relation of sleep difficulties to fatigue, mood and disability in chronic fatigue syndrome.

Morriss, R K, Wearden, A J, Battersby, L·Journal of psychosomatic research·1997

This study looked at sleep problems in 69 people with ME/CFS who had no mental health conditions and 58 with ME/CFS plus depression or anxiety. Researchers found that sleep difficulties are common in ME/CFS but are usually caused by the illness itself rather than depression. People with ME/CFS often took naps and woke up from pain, and when their sleep got worse, their ME/CFS symptoms often worsened too.

E2 ModerateCohortPEM unclearCross-Sectional

Sleep anomalies in the chronic fatigue syndrome. A comorbidity study.

Fischler, B, Le Bon, O, Hoffmann, G et al.·Neuropsychobiology·1997

This study examined sleep patterns in 49 ME/CFS patients compared to 20 healthy people using overnight sleep monitoring. Patients with ME/CFS had difficulty falling asleep and staying asleep, and spent less time in deep, restorative stage 4 sleep. These sleep problems were distinctive enough that researchers could correctly identify who had ME/CFS based on sleep patterns alone.

E2 ModerateCohortPEM not requiredCross-Sectional

Do patients with "pure" chronic fatigue syndrome (neurasthenia) have abnormal sleep?

Sharpley, A, Clements, A, Hawton, K et al.·Psychosomatic medicine·1997

This study compared sleep in 20 people with ME/CFS (who did not have depression, anxiety, or other sleep disorders) to 20 healthy people. Although ME/CFS patients reported feeling like they had poor, unrefreshing sleep and took daytime naps, objective sleep measurements showed surprisingly few differences—most patients actually slept a normal amount of time at night, though they spent longer lying awake after first falling asleep.

E2 ModerateBehavioralPEM not requiredObservational

An open study of the efficacy and adverse effects of moclobemide in patients with the chronic fatigue syndrome.

White, P D, Cleary, K J·International clinical psychopharmacology·1997

This study tested whether a medication called moclobemide could help people with ME/CFS. Researchers gave 49 patients the drug for 6 weeks and found small improvements in fatigue, depression, and anxiety. The medication worked better for patients who also had depression, with half of them feeling much better, compared to only about one-fifth of those without depression.

E2 ModerateCohortPEM unclearCross-Sectional

Insulin-like growth factor-I (somatomedin C) levels in chronic fatigue syndrome and fibromyalgia.

Buchwald, D, Umali, J, Stene, M·The Journal of rheumatology·1996

Researchers tested whether people with ME/CFS have lower levels of a growth hormone called IGF-I, which had previously been found to be low in fibromyalgia patients. They measured IGF-I levels in 15 people with ME/CFS, 15 with both ME/CFS and fibromyalgia, 27 with fibromyalgia alone, and 15 healthy volunteers. The study found no significant differences in IGF-I levels between any of the patient groups and healthy controls, suggesting that low IGF-I may not be a key feature of ME/CFS.

E2 ModerateCohortPEM not requiredCross-Sectional

Periodic K-alpha sleep EEG activity and periodic limb movements during sleep: comparisons of clinical features and sleep parameters.

MacFarlane, J G, Shahal, B, Mously, C et al.·Sleep·1996

This study examined a specific brain wave pattern during sleep called K-alpha activity and compared it to periodic leg movements during sleep. Researchers found that patients with K-alpha activity were predominantly women, younger, and more likely to have fibromyalgia and chronic fatigue syndrome, while also experiencing unrefreshing sleep, stomach problems, and muscle pain.

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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.