Notable studies

This page lists published ME/CFS studies that are notable, for particularly interesting findings, for controversial findings, or for their quality or their size.

Studies

• Epidemiology
• Immunological
• Metabolic
• Neurological
• Treatment
• Psychological

General category	Year	Study title & Author(s)	Notes	Cohort size	Blinded (double, single, not)
Epidemiological	2015	Institute of Medicine report Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness Ellen Wright Clayton (Chair), Margarita Alegría, Lucinda Bateman, Lily Chu, Charles Cleeland, Ronald Davis, Betty Diamond, Theodore Ganiats, Betsy Keller, Nancy Klimas, A Martin Lerner, Cynthia Mulrow, Benjamin Natelson, Peter Rowe, Michael Shelanski
Epidemiological	2015	Pathways to prevention report Green CR, Cowan P, Elk R, O'Neil KM, Rasmussen AL
Epidemiological	2014	Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008–2012 Bakken IJ, Tveito K, Gunnes N, Ghaderi S, Stoltenberg C, Trogstad L, Håberg SE, Magnus P
Epidemiological	2013	The prevalence of chronic fatigue syndrome/myalgic encephalomyelitis: a meta-analysis Johnston S, Brenu EW, Staines D, Marshall-Gradisnik SM
Epidemiological	2011	Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care Luis Nacul, Eliana Lacerda, Derek Pheby, Peter Campion, Mariam Molokhia, Shagufta Fayyaz, Jose CDC Leite, Fiona Poland, Amanda Howe, Maria L Drachler
Epidemiological	2007	The burden of disease and injury in Australia 2003 Begg S, Vos T, Barker B, Stevenson C, Stanley L, Lopez A
Epidemiological	2006	Prolonged Illness after infectious mononucleosis is associated with altered immunity but not with increased viral load Cameron B, Bharadwaj M, Burrows J, Fazou C, Wakefield D, Hickie I, Ffrench R, Khanna R and Lloyd A	See also Model of Post Infective Fatigue Forming: the Dubbo Studies
Epidemiological	2006	Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr virus Vernon S, Whistler T, Cameron B, Hickie I, Reeves WC and Lloyd A	See also Model of Post Infective Fatigue Forming: the Dubbo Studies
Epidemiological	2006	Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A
Epidemiological	2005	A systematic review describing the prognosis of chronic fatigue syndrome Ruth Cairns, Matthew Hotopf
Epidemiological	1996	Health status in patients with chronic fatigue syndrome and in general population and disease comparison groups Komaroff AL, Fagioli LR, Doolittle TH, Gandek B, Gleit MA, Guerriero RT, Kornish RJ 2nd, Ware NC, Ware JE Jr, Bates DW
Immunological	2019	A nanoelectronics-blood-based diagnostic biomarker for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) Rahim Esfandyarpour, Alex Kashi, Mohsen Nemat-Gorgani, Julie Wilhelmy, and Ron W. Davis |		19
Immunological	2015	Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome Landi A, Broadhurst D, Vernon SD, Tyrrell DL, Houghton M
Immunological	2015	Distinct plasma immune signatures in ME/CFS are present early in the course of illness Hornig M, Montoya JG, Klimas NG, Levine S, Felsenstein D, Bateman L, Peterson DL, Gottschalk CG, Schultz AF, Che X, Eddy ML, Komaroff AL, Lipkin WI
Immunological	2014	Deficient EBV-specific B-and T-cell response in patients with chronic fatigue syndrome Madlen Loebel, Kristin Strohschein, Carolin Giannini, Uwe Koelsch, Sandra Bauer, Cornelia Doebis, Sybill Thomas, Nadine Unterwalder, Volker von Baehr, Petra Reinke, Michael Knops, Leif G. Hanitsch, Christian Meisel, Hans-Dieter Volk, Carmen Scheibenbogen
Immunological	2012	Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis Ekua Brenu, Mieke L van Driel, Donald Staines, Kevin J Ashton, Sharni L Hardcastle, James Keane, Lotti Tajouri, Daniel Peterson, Sandra B Ramos, Sonya Marshall-Gradisnik
Immunological	2011	Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study Øystein Fluge , Ove Bruland, Kristin Risa, Anette Storstein, Einar K. Kristoffersen, Dipak Sapkota, Halvor Næss, Olav Dahl, Harald Nyland, Olav Mella
Immunological	2010	Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26 Fletcher MA, Zeng XR, Maher K
Immunological	2008	Neuroendocrine and immune network remodeling in chronic fatigue syndrome: an exploratory analysis Fuite J, Suzanne Vernon, Gordon Broderick
Immunological	2008	Cytokine Polymorphisms Have a Synergistic Effect on Severity of the Acute Sickness Response to Infection Vollmer-Conna U, Piraino B, Cameron B
Immunological	2007	Postinfective fatigue syndrome is not associated with altered cytokine production Vollmer-Conna U, Cameron B, Pavlovic D
Immunological	2006	A first study of cytokine genomic polymorphisms in CFS: positive association of TNF‐857 and IFNgamma 874 rare alleles Carlo‐Stella N, Badulli C, De S
Immunological	2005	Association of chronic fatigue syndrome with human leucocyte antigen class II alleles Smith J, Fritz EL, Jonathan Kerr
Metabolic	2016	Metabolic features of chronic fatigue syndrome Ronald Davis (Editor), Robert Naviaux, Jane C. Naviaux, Kefeng Li, A. Taylor Bright, William A. Alaynick, Lin Wang, Asha Baxter, Neil Nathan, Wayne Anderson, Eric Gordon	Metabolomics showed that chronic fatigue syndrome is a highly concerted hypometabolic response to environmental stress that traces to mitochondria and was similar to the classically studied developmental state of dauer.
Metabolic	2014	Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO2peak indicates functional impairment Betsy Keller, John Pryor, Ludovic Giloteaux
Metabolic	2012	Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls AT White, Alan Light, RW Hughen, TA Vanhaitsma, Kathleen Light
Metabolic	2009	Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects Alan Light, AT White, RW Hughen, Kathleen Light
Neurological	2016	Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study. Shan ZY, Kwiatek R, Burnet R, Del Fante P, Staines DR, Marshall-Gradisnik SM, Barnden LR
Neurological	2015	Phase relationships are only measurable by the qEEG, giving us a unique window into the ME disease process Marcie Zinn, Mark Zinn, Leonard Jason	See also Phase Reset of the Default Mode Network.
Neurological	2015	There is poor agreement among researchers and clinicians about case definitions. Key domains are discussed. Leonard Jason, Marcie Zinn, Mark Zinn	See also Lack of Agreement in Case Definitions hampers research.
Neurological	2015	Right arcuate fasciculus abnormality in chronic fatigue syndrome Michael Zeineh, Kang J, Atlas SW, Raman MM, Reiss AL, Jane Norris, Valencia I, Jose Montoya
Neurological	2007	Symptoms of autonomic dysfunction in chronic fatigue syndrome Julia Newton, O Okonkwo, K Sutcliffe, Seth A, Shin J, Jones DE
Treatment	2015	Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome Øystein Fluge, Olav Mella, Madlen Loebel, Patricia Grabowski, Heidecke H, Bauer S, Hanitsch LG, Wittke K, Meisel C, Reinke P, Volk HD, Carmen Scheibenbogen
Treatment	2015	B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment Øystein Fluge, Olav Mella, Risa K, Lunde S, Alme K, Rekeland IG, Sapkota D, Kristoffersen EK, Sørland K, Bruland O, Dahl O
Treatment	2013	Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls Amolak Bansal, AS Bradley, B Ford
Treatment	2013	Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study Jarred Younger, Sean Mackey
Treatment	2012	The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy Thomas Borody, Anna Nowak, Sarah Finalayson
Treatment	2011	Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study Øystein Fluge, Olav Mella, Bruland O, Risa K, Storstein A, Kristoffersen EK, Sapkota D, Næss H, Dahl O, Nyland H
Treatment	2010	Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels Jarred Younger, Noor N, McCue R, Mackey S
Treatment	2009	Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series Øystein Fluge, Olav Mella
Treatment	2008	Normalization of leaky gut in Chronic Fatigue Syndrome (CFS) is accompanied by a clinical improvement Michael Maes, Jean-Claude Leunis
Psychological	2011	The PACE trial Peter White, Kimberly A Goldsmith, AL Johnson, L Potts, Rebecca Walwyn, Julia C DeCesare, Hannah L Baber, Mary Burgess, Lucy V Clark, Diane L Cox, Jessica Bavinton, BJ Angus, Gabrielle Murphy, Maurice Murphy, Hazel O'Dowd, David Wilks, P McCrone, Trudie Chalder, Michael Sharpe
Psychological	2005	The Placebo Response in the Treatment of Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis Hyong Jin Cho, Matthew Hotopf, Simon Wessely	Found that the placebo response was actually lower in CFS patients
Psychological	2014	Exercise therapy for chronic fatigue syndrome Cochrane review: Lillebeth Larun, Kjetil G. Brurberg, Jan Odgaard-Jensen, Jonathan R Price

See also

• Notable studies (category)
• Diagnostic biomarker
• Research terminology

Learn more

• Research publications 1956-2016 - ME Research UK

See myalgic encephalomyelitis.

See chronic fatigue syndrome.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

creatine (CR) - A natural substance that turns into creatine phosphate in the body, which helps make ATP. ATP provides the energy for muscles Often taken as a supplement to improve sports performance. (Learn more: www.webmd.com)

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

See Centers for Disease Control and Prevention.

metabolomics The analysis of the chemical metabolism within cells, tissues or organisms. The term is often used to refer to the full set of metabolites found in a cell in a given environment.