Evidence browser

[Conditions, controversies and contradictions between Central Sensitivity Syndrome and Depressive Disorders].

Maresca, Tomás, Covini, Elvira, Mato, Andrea Márquez López·Vertex (Buenos Aires, Argentina)·2013

This review article explains Central Sensitivity Syndrome (CSS), a condition where the nervous system becomes overly sensitive to pain and other stimuli, and how it relates to ME/CFS and fibromyalgia. The authors describe how CSS differs from depression, even though people with CSS often experience depression as well, by comparing how the body's stress hormones, sleep patterns, and immune systems function differently in each condition.

Psychobiotics: a novel class of psychotropic.

Dinan, Timothy G, Stanton, Catherine, Cryan, John F·Biological psychiatry·2013

This review examines 'psychobiotics'—beneficial bacteria that may help with mood and mental health by producing brain chemicals like serotonin. These bacteria communicate with the brain through the gut-brain connection. Early research in animals and some patient studies suggests they might reduce depression, anxiety, and fatigue symptoms, possibly by lowering inflammation and stress hormone levels.

E3 PreliminaryBehavioralPEM not requiredLongitudinal

Fibromyalgia Symptom Reduction by Online Behavioral Self-monitoring, Longitudinal Single Subject Analysis and Automated Delivery of Individualized Guidance.

Collinge, William, Yarnold, Paul, Soltysik, Robert·North American journal of medical sciences·2013

This study tested a website tool called SMARTLog that helps people with fibromyalgia track their symptoms and receive personalized feedback. Patients who used the tool several times a week for a few months reported improvements in pain, fatigue, memory, mood, and sleep. The more consistently people used the tool, the greater their symptom improvements tended to be.

E3 PreliminaryBehavioralPEM not requiredCase-Control

[Back pain and somatisation].

Jenewein, Josef·Therapeutische Umschau. Revue therapeutique·2013

Back pain is common in people with somatoform disorders, where physical symptoms occur without a clear medical cause. About 10–20% of back pain patients have this type of disorder, and up to half also experience depression or anxiety. Doctors need to distinguish somatoform pain from other conditions like fibromyalgia and ME/CFS. Treatment typically involves talk therapy, relaxation techniques, physical activity, and sometimes antidepressant medications.

Pain and Sensitization

Psychological stress contributed to the development of low-grade fever in a patient with chronic fatigue syndrome: a case report.

Oka, Takakazu, Kanemitsu, Yoshio, Sudo, Nobuyuki et al.·BioPsychoSocial medicine·2013

This study followed one ME/CFS patient who noticed her low-grade fevers got worse during stressful work situations. Researchers had her recall stressful memories while measuring her body temperature and stress hormones. Her core temperature rose by about 1°C during stress, but blood markers related to fever-causing inflammation didn't change, suggesting stress hormones (not immune inflammation) triggered the temperature increase.

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Method Issues in Epidemiological Studies of Medically Unexplained Symptom-based Conditions in Veterans.

Coughlin, Steven S, McNeil, Rebecca B, Provenzale, Dawn T et al.·Journal of military and veterans' health·2013

This study examined how researchers diagnose ME/CFS and related conditions in veterans, particularly those who served in the 1990-1991 Gulf War. The researchers found that many veterans had other medical conditions that could complicate or mask ME/CFS diagnosis. The study highlights that how doctors define and diagnose these conditions matters a lot, and different approaches can lead to very different results.

Diagnostics

Loss of stress response as a consequence of viral infection: implications for disease and therapy.

Hooper, Philip L, Hightower, Lawrence E, Hooper, Paul L·Cell stress & chaperones·2012

This paper suggests that viral infections may damage the body's ability to handle stress at the cellular level, making tissues more vulnerable to injury. Rather than looking for one specific virus causing ME/CFS, the authors propose that ME/CFS might result from a general, nonspecific cellular damage response that occurs after many types of viral infections. Understanding this mechanism could open new treatment possibilities for conditions that have not responded well to existing therapies.

E3 PreliminaryMechanismPEM not requiredObservational

Molecular signatures of peripheral blood mononuclear cells during chronic interferon-α treatment: relationship with depression and fatigue.

Felger, J C, Cole, S W, Pace, T W W et al.·Psychological medicine·2012

When patients received interferon-alpha treatment (used for hepatitis C and cancer), researchers looked at immune cell genes to understand why the treatment causes depression and fatigue. They found that one gene called OAS2, previously linked to chronic fatigue syndrome, was especially active in patients who developed depression and fatigue during treatment. This suggests that immune system changes may directly contribute to these symptoms.

Inflammatory fatigue and sickness behaviour - lessons for the diagnosis and management of chronic fatigue syndrome.

Arnett, S V, Clark, I A·Journal of affective disorders·2012

This review examines how inflammation in the body can cause extreme tiredness and sickness-like symptoms similar to those seen in ME/CFS. The authors looked at how inflammatory chemicals in the brain trigger the body's sickness response—similar to how you feel when fighting an infection—and found that this same process may be happening in ME/CFS patients. They suggest that understanding this connection could help doctors diagnose and treat ME/CFS more effectively.

Can persistent Epstein-Barr virus infection induce chronic fatigue syndrome as a Pavlov reflex of the immune response?

Agliari, Elena, Barra, Adriano, Vidal, Kristian Gervasi et al.·Journal of biological dynamics·2012

This study proposes a theory for how ME/CFS might develop: a long-lasting Epstein-Barr virus infection could train the immune system to stay "stuck" in a highly activated state, even after the virus is controlled or cleared. Using mathematical models, researchers suggest that prolonged virus exposure creates strong connections between different immune cells, similar to how the brain forms lasting memories—a concept known as Pavlov's reflex. This could explain why ME/CFS causes persistent inflammation and exhaustion without an obvious ongoing cause.

E3 PreliminaryMechanismPEM not requiredObservational

Lack of endogenous pain inhibition during exercise in people with chronic whiplash associated disorders: an experimental study.

Van Oosterwijck, Jessica, Nijs, Jo, Meeus, Mira et al.·The journal of pain·2012

This study compared how the body responds to exercise in people with chronic whiplash injury versus healthy people. Researchers found that pain sensitivity actually increased (got worse) after exercise in whiplash patients, while it decreased (improved) in healthy controls. Importantly, gentle, self-paced exercise caused fewer symptom flare-ups than harder, fixed-intensity exercise, suggesting that how exercise is done matters greatly for people with this condition.

Post-Exertional Malaise

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Phylogenetic and biological analysis of a laboratory-generated gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV).

Ma, Xiaochu, Zhou, Shiying, Wei, Meili et al.·Virus genes·2012

This study investigated whether XMRV, a virus previously thought to be associated with chronic fatigue syndrome, could actually infect human cells. Researchers found that XMRV is a laboratory-made virus created accidentally during experiments with mouse tissues, not a naturally occurring pathogen. Testing showed that XMRV cannot infect human immune cells, suggesting it is unlikely to cause disease in people.

Multiple sources of contamination in samples from patients reported to have XMRV infection.

Kearney, Mary F, Spindler, Jonathan, Wiegand, Ann et al.·PloS one·2012

Researchers tested blood samples from ME/CFS patients that were previously reported to contain a virus called XMRV. Using careful testing methods, they found that the virus-like sequences in patient blood samples were actually contamination from mouse DNA used in lab experiments, not the XMRV virus itself. When they did find actual XMRV virus, it appeared in healthy control samples and came from cross-contamination in the lab rather than from patient infections.

A role for corticosteroid-binding globulin variants in stress-related disorders.

Marathe, Chinmay S, Torpy, David J·Expert review of endocrinology & metabolism·2012

This review examines how genetic variations in a protein called corticosteroid-binding globulin (CBG) may influence whether someone develops ME/CFS, fibromyalgia, or chronic pain. CBG helps transport cortisol (the body's stress hormone) in the blood, and when this protein doesn't work properly, it may affect how the body responds to stress. The researchers looked at evidence from genetic studies and animal models suggesting that inherited differences in the CBG gene could increase someone's risk of developing these stress-related conditions.

Endocrine Disruption

Long-term infection and vertical transmission of a gammaretrovirus in a foreign host species.

Sakuma, Toshie, Tonne, Jason M, Malcolm, Jessica A et al.·PloS one·2012

Researchers studied a virus called XMRV that can jump between animal species to understand how viruses adapt when they infect new hosts. They infected a type of mouse with XMRV and watched what happened over a year, including whether the virus could be passed to offspring. The mice stayed healthy and the virus didn't spread much to the next generation, suggesting that while the virus can infect new species, it doesn't easily take hold or spread.

Identification of XMRV infection-associated microRNAs in four cell types in culture.

Mohan, Ketha V K, Devadas, Krishnakumar, Sainath Rao, Shilpakala et al.·PloS one·2012

This study looked at how a virus called XMRV affects the behavior of microRNAs—tiny molecules that control how genes are expressed—in different types of human cells grown in the laboratory. Researchers infected four different cell types with XMRV and measured changes in microRNA patterns at different time points. They found that certain microRNAs changed in response to the virus infection.

E3 PreliminaryMechanismPEM unclearCase-Control

Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Brenu, Ekua W, Ashton, Kevin J, van Driel, Mieke et al.·Journal of affective disorders·2012

Researchers studied tiny molecules called microRNAs in immune cells from people with ME/CFS and healthy controls. They found that people with ME/CFS have lower levels of certain microRNAs in their immune cells, which may explain why their immune systems don't work as well. These microRNA changes could be useful biomarkers—like a fingerprint—to help diagnose or understand ME/CFS.

E3 PreliminaryMechanismPEM unclearCross-Sectional

The in vivo infusion of hydrogen peroxide induces oxidative stress and differentially affects the activities of small intestinal carbohydrate digestive enzymes in the neonatal pig.

Lackeyram, D, Mine, Y, Widowski, T et al.·Journal of animal science·2012

Researchers gave young pigs either hydrogen peroxide (a substance that causes oxidative stress, similar to cellular damage) or saline over 10 days to study how oxidative stress might affect ME/CFS. Pigs given hydrogen peroxide showed reduced antioxidant levels, less physical activity, and decreased ability to digest certain carbohydrates in their intestines. This suggests that oxidative stress may interfere with how the gut breaks down food, which could contribute to fatigue and other ME/CFS symptoms.

No biological evidence of XMRV in blood or prostatic fluid from prostate cancer patients.

Mendoza, Ramon, Silverman, Robert H, Klein, Eric A et al.·PloS one·2012

Researchers tested blood and fluid samples from prostate cancer patients to see if they contained XMRV, a virus that was once thought to cause chronic fatigue syndrome. They found no evidence of the virus in any of the samples, including in nine patients who had previously tested positive for XMRV. This study supports the growing scientific consensus that XMRV does not actually infect humans.