Evidence browser

E3 PreliminaryCohortPEM not requiredCase-Control

Functional genomics of serotonin receptor 2A (HTR2A): interaction of polymorphism, methylation, expression and disease association.

Falkenberg, Virginia R, Gurbaxani, Brian M, Unger, Elizabeth R et al.·Neuromolecular medicine·2011

This study looked at how a specific genetic variation in the serotonin receptor 2A gene (HTR2A) affects how active this gene is in people with ME/CFS. The researchers found that this gene is turned up (overactive) in ME/CFS patients, and that this overactivity is influenced by both the genetic variant someone inherits and how stress hormones like cortisol affect the gene's activity. Think of it like a volume knob on a radio that can be turned up or down depending on your genes and stress levels.

Sympathetic neural hyperalgesia edema syndrome, a frequent cause of pelvic pain in women, mistaken for Lyme disease with chronic fatigue.

Check, J H, Cohen, R·Clinical and experimental obstetrics & gynecology·2011

This study describes a woman who was diagnosed with Lyme disease and treated with antibiotics for chronic fatigue, but her symptoms didn't improve. Doctors then tested her ability to excrete water from her body and found it was impaired, suggesting a problem with her sympathetic nervous system (the part that controls automatic body functions). When she was treated with a stimulant medication instead, she improved significantly.

Diagnostics

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

DNA extraction columns contaminated with murine sequences.

Erlwein, Otto, Robinson, Mark J, Dustan, Simon et al.·PloS one·2011

Researchers discovered that the plastic columns used to extract and purify DNA in laboratory tests were contaminated with mouse DNA sequences. When they used these contaminated columns and ran sensitive DNA detection tests, they got false positive results that looked like they had found viral sequences (XMRV) when they actually hadn't. This is important because some earlier studies claimed to find XMRV in ME/CFS patients, but this contamination problem means those results may have been unreliable.

Sleep and fatigue in mice infected with murine gammaherpesvirus 68.

Olivadoti, Melissa D, Weinberg, Jason B, Toth, Linda A et al.·Brain, behavior, and immunity·2011

Researchers infected mice with a virus similar to one that has been linked to chronic fatigue syndrome in humans. They found that infected mice showed fatigue-like symptoms (reduced activity, altered sleep and body temperature) during the first 1-2 weeks of infection. Notably, when these mice were given a bacterial toxin challenge a month later, they had much stronger and longer-lasting reactions than uninfected mice, suggesting that latent viral infection may make the body oversensitive to future immune challenges.

E3 PreliminaryCohortPEM not required

Decades of delayed diagnosis in 4 levodopa-responsive young-onset monogenetic parkinsonism patients.

Ling, Helen, Braschinsky, Mark, Taba, Pille et al.·Movement disorders : official journal of the Movement Disorder Society·2011

This study describes four young patients who were initially misdiagnosed with psychological movement disorders or chronic fatigue syndrome, but actually had a genetic form of Parkinson's disease. Their misdiagnosis lasted 10 to 23 years before the correct diagnosis was made. Once they received the correct treatment with levodopa medication, they all improved significantly, showing that the right diagnosis and treatment can make a major difference.

Diagnostics

E3 PreliminaryReviewPEM not requiredReview-Narrative

The common immunogenic etiology of chronic fatigue syndrome: from infections to vaccines via adjuvants to the ASIA syndrome.

Rosenblum, Hemda, Shoenfeld, Yehuda, Amital, Howard·Infectious disease clinics of North America·2011

ME/CFS is a long-lasting illness of extreme fatigue and other symptoms that often starts suddenly like a flu. This review examines several theories about what might cause ME/CFS, including infections, genetic factors, hormone problems, immune system dysfunction, and psychological stress. The authors discuss a newer condition called ASIA syndrome, which involves autoimmune reactions that may be triggered by vaccine adjuvants (ingredients added to vaccines to boost immune response).

E3 PreliminaryReviewPEM not requiredReview-Narrative

Role of infection and neurologic dysfunction in chronic fatigue syndrome.

Komaroff, Anthony L, Cho, Tracey A·Seminars in neurology·2011

This review examines the connection between infections and ME/CFS, looking at decades of cases where people developed long-lasting fatigue after infections. The authors found evidence that certain viruses and bacteria can cause persistent infections that trigger and maintain ME/CFS symptoms by affecting the nervous system and triggering ongoing immune responses. While no single infection has been proven to cause ME/CFS in all cases, the pattern suggests that chronic infections may be important triggers in some people with the illness.

Neuroinflammation

NeuroinflammationImmune System

Depression's multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways.

Maes, Michael, Kubera, Marta, Obuchowiczwa, Ewa et al.·Neuro endocrinology letters·2011

This review explains why depression often occurs alongside many other diseases, including ME/CFS, autoimmune conditions, heart disease, and neurodegenerative disorders. The common link appears to be activation of inflammatory and oxidative stress pathways in both the brain and body. These pathways may act like a 'warning system' that produces depression symptoms such as fatigue, anxiety, and physical discomfort when the body detects a threat.

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

Classifying medication use in clinical research.

Rizzo, Dorrie, Creti, Laura, Bailes, Sally et al.·Journal of primary care & community health·2011

Researchers created a simple system for organizing and grouping the medicines that patients take during medical studies. They tested this organizational method on patients with ME/CFS and sleep apnea to see if different groups of patients tend to take different combinations of medications. They found five main medicine categories, and importantly, the pattern of medicines taken by ME/CFS patients was quite different from sleep apnea patients, possibly reflecting different views about what causes these conditions.

E3 PreliminaryBehavioralPEM not requiredCase-Control

Pain neurophysiology education improves cognitions, pain thresholds, and movement performance in people with chronic whiplash: a pilot study.

Van Oosterwijck, Jessica, Nijs, Jo, Meeus, Mira et al.·Journal of rehabilitation research and development·2011

This small study tested whether teaching patients with chronic neck pain from whiplash about how pain works in the body could help them feel better. Six patients received this education, and researchers found that afterward, patients had less fear of movement, used healthier coping strategies, reported less disability, and could move their necks with less pain.

Pain and Sensitization

Heterologous immunity: immunopathology, autoimmunity and protection during viral infections.

Selin, Liisa K, Wlodarczyk, Myriam F, Kraft, Anke R et al.·Autoimmunity·2011

When your body fights off infections, your immune system sometimes creates responses that can cross-react with other pathogens or even your own tissues. Most of the time this is helpful and protects you, but in some people it can trigger harmful immune reactions. This review explores how repeated infections with different viruses and bacteria might cause the immune system to become dysregulated, potentially contributing to conditions like chronic fatigue syndrome.

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

Investigation of xenotropic murine leukemia virus-related virus (XMRV) in human and other cell lines.

Williams, Dhanya K, Galvin, Teresa A, Ma, Hailun et al.·Biologicals : journal of the International Association of Biological Standardization·2011

Researchers tested several types of cells commonly used in laboratories and vaccine development to see if they contained XMRV, a virus that had been suggested as a possible cause of ME/CFS. Using sensitive detection methods, they found no evidence of XMRV in any of the cell lines they tested, which is reassuring for the safety of biological products made from these cells.

NF-kappaB activation stimulates transcription and replication of retrovirus XMRV in human B-lineage and prostate carcinoma cells.

Sakakibara, Shuhei, Sakakibara, Kaori, Tosato, Giovanna·Journal of virology·2011

This study examined how inflammation in the body can affect a virus called XMRV. Researchers found that when inflammatory signals (like TNF-α) are activated in cells, they can turn up the volume on XMRV production. This suggests that conditions causing inflammation or certain viral infections might help XMRV spread in the body.

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

Identification of Phosphoglycerate Kinase 1 (PGK1) as a reference gene for quantitative gene expression measurements in human blood RNA.

Falkenberg, Virginia R, Whistler, Toni, Murray, Janna' R et al.·BMC research notes·2011

Researchers studying ME/CFS need reliable ways to measure gene activity in blood samples. This study found that a gene called PGK1 is a stable and reliable 'reference point' for comparing gene measurements across different blood collection methods and sample types. Using a single stable reference gene like PGK1 makes it easier for scientists to get accurate, comparable results when searching for blood-based biomarkers of ME/CFS.

Biomarkers

E3 PreliminaryCohortPEM not requiredCase-Control

Adrenal histoplasmosis: a case series and review of the literature.

Larbcharoensub, Noppadol, Boonsakan, Paisarn, Aroonroch, Rangsima et al.·The Southeast Asian journal of tropical medicine and public health·2011

This study describes seven cases of a rare fungal infection (histoplasmosis) that affected the adrenal glands—small organs that help manage stress and energy in the body. All patients experienced chronic fatigue as their main symptom, and most recovered after treatment. While this infection is uncommon, it shows that certain fungal infections can cause fatigue-like illness and should be considered when evaluating patients with unexplained chronic tiredness.

Polysaccharide of radix pseudostellariae improves chronic fatigue syndrome induced by poly I:C in mice.

Sheng, Rong, Xu, Xianxiang, Tang, Qin et al.·Evidence-based complementary and alternative medicine : eCAM·2011

Researchers tested whether a natural plant compound called polysaccharide from Radix Pseudostellariae (PRP) could help mice recover from fatigue-like symptoms. They found that mice given PRP before being exposed to a virus-like trigger showed less fatigue and better recovery of normal immune and stress hormone function compared to untreated mice.

Nitric oxide modulation in protective role of antidepressants against chronic fatigue syndrome in mice.

Kumar, Anil, Garg, Ruchika, Gaur, Vaibhav et al.·Indian journal of pharmacology·2011

This study used mice exposed to repeated stress (forced swimming) to create a model similar to ME/CFS, then tested whether two common antidepressants could help. The researchers found that these antidepressants reduced fatigue-like behavior and signs of cellular damage in the brain, possibly by affecting a molecule called nitric oxide. The findings suggest antidepressants might work partly through protecting the brain from oxidative stress.

E3 PreliminaryDiagnosticPEM not requiredObservational

The search for reliable biomarkers of disease in multiple chemical sensitivity and other environmental intolerances.

De Luca, Chiara, Raskovic, Desanka, Pacifico, Valeria et al.·International journal of environmental research and public health·2011

This review examines why some people develop severe reactions to chemicals, foods, and environmental exposures at levels that shouldn't cause harm. The authors argue these conditions—including ME/CFS, fibromyalgia, and multiple chemical sensitivity—are real biological disorders, not just psychological problems. They explore evidence that problems with how the body detoxifies and handles harmful substances, along with imbalances in antioxidant protection, may be key to understanding these diseases.

Energy Metabolism

Supervised selection of single nucleotide polymorphisms in chronic fatigue syndrome.

Cifuentes, Ricardo A, Barreto, Emiliano·Biomedica : revista del Instituto Nacional de Salud·2011

This study examined whether specific genetic variations (single nucleotide polymorphisms or SNPs) could help predict who has ME/CFS. Researchers used a mathematical approach to identify the most useful genetic markers and found a combination of two genetic variants that correctly identified ME/CFS in about 73% of cases. When this genetic profile was combined with specific symptoms like muscle pain or sinus problems, the accuracy improved to over 87%.

Biomarkers