Evidence browser

E2 ModerateCohortPEM not requiredLongitudinal

Use and Perceived Helpfulness of Different Intervention Strategies in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Depression.

Dorczok, Marie Celine, Mossaheb, Nilufar, Mittmann, Gloria et al.·Journal of clinical medicine·2026

This study compared how people with ME/CFS and depression use different treatments and how helpful they find them. People with ME/CFS tried a much wider variety of interventions—especially pacing strategies and supplements aimed at energy—and found many of them helpful. In contrast, people with depression mainly used psychotherapy and antidepressants, which align with standard medical guidelines. The difference likely reflects that ME/CFS currently lacks established treatment guidelines, while depression has well-tested approaches.

Interventions

A longitudinal study on the correlation between symptom clusters and disease-specific health status in older adults with chronic obstructive pulmonary disease during pulmonary rehabilitation.

Yang, Jinghua, Xu, Na, Liang, Mengyao·Frontiers in public health·2026

This study followed 184 older adults with COPD (a lung disease) over 12 weeks of rehabilitation to understand how their symptoms changed and how those changes affected their quality of life. Researchers found that symptoms shifted over time—starting with breathing problems and tiredness, then developing muscle soreness and swelling with exercise, and eventually centering on fatigue and social withdrawal. The type of symptoms that most affected patients' wellbeing also changed throughout rehabilitation, suggesting that different support may be needed at different stages of recovery.

E2 ModerateCohortPEM requiredCross-Sectional

Distinct functional connectivity patterns in myalgic encephalomyelitis and long COVID patients during cognitive fatigue: a 7 Tesla task-fMRI study.

Inderyas, Maira, Thapaliya, Kiran, Marshall-Gradisnik, Sonya et al.·Journal of translational medicine·2026

This study used advanced brain imaging to compare how the brains of ME/CFS patients, long COVID patients, and healthy people work during a challenging thinking task. Researchers found that patients' brains show different patterns of communication between regions compared to healthy controls, particularly in areas related to motivation, memory, and emotional processing. These brain differences appeared to worsen as fatigue built up during the task.

E2 ModerateBehavioralPEM not requiredObservational

Familial coaggregation and shared familiality of functional and internalizing disorders in the Lifelines cohort.

Bos, Martje, Monden, Rei, Wray, Naomi R et al.·Psychological medicine·2025

This study looked at whether ME/CFS, irritable bowel syndrome, and fibromyalgia run in families, and whether they share common causes with depression and anxiety disorders. Researchers studied over 150,000 people in the Netherlands and found that these conditions do tend to cluster in families—if a relative has one of these conditions, your risk of having it is higher. ME/CFS showed the strongest family connection and was most closely linked to depression.

Chronic fatigue syndrome, depression, and anxiety symptoms due to relapsing-remitting multiple sclerosis are associated with reactivation of Epstein-Barr virus and Human Herpesvirus 6.

Maes, Michael, Almulla, Abbas F, Vojdani, Elroy et al.·Neuro endocrinology letters·2025

This study looked at whether reactivation of two common viruses—Epstein-Barr virus (EBV) and Human herpesvirus 6 (HHV-6)—are connected to fatigue, depression, and anxiety in people with a type of multiple sclerosis called RRMS. Researchers measured immune responses (antibodies) to these viruses in MS patients and healthy controls, and found that higher antibody levels were strongly linked to worse fatigue and mood symptoms. The findings suggest that when these dormant viruses become active in the body, they may trigger or worsen fatigue and psychiatric symptoms.

Immune System

E2 ModerateBehavioralPEM unclearCross-Sectional

Comparative Study Between Cognitive Phenotypes of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Multiple Sclerosis.

Aoun Sebaiti, Mehdi, Oubaya, Nadia, Gounden, Yannick et al.·Diagnostics (Basel, Switzerland)·2025

This study compared thinking and memory problems in ME/CFS patients with those in multiple sclerosis (MS) patients, since both conditions can cause similar cognitive issues, fatigue, and pain. Researchers tested 40 people with ME/CFS and 40 with MS using standard memory and attention tests. They found that ME/CFS patients have a specific pattern of cognitive difficulties, particularly problems with consolidating (storing) new information in memory, which is distinct from MS.

Cognitive Impairment

Psychosocial Nursing Diagnoses of Individuals With Myalgic Encephalomyelitis-Chronic Fatigue Syndrome: A Descriptive Study.

Oter-Quintana, Cristina, Alameda-Cuesta, Almudena, Brito-Brito, Pedro Ruymán et al.·Nursing open·2025

This study looked at the emotional and psychological challenges that people with ME/CFS commonly experience. Researchers surveyed 48 adults with ME/CFS and found that most experienced feelings of powerlessness, difficulty coping, and fear. The study identified three different groups of patients: one group with more severe symptoms and greater emotional distress, and two other groups with milder symptoms who were still working or retired.

E2 ModerateCohortPEM requiredLongitudinal

An In-Depth Exploration of the Autoantibody Immune Profile in ME/CFS Using Novel Antigen Profiling Techniques.

Germain, Arnaud, Jaycox, Jillian R, Emig, Christopher J et al.·International journal of molecular sciences·2025

This study looked for specific immune proteins called autoantibodies in the blood of ME/CFS patients to see if they might be causing the illness. Researchers tested over 7,500 different immune markers using advanced laboratory techniques in 172 people. Surprisingly, they did not find significant differences in autoantibodies between ME/CFS patients and healthy controls, though they did notice some subtle patterns between men and women with ME/CFS that warrant further investigation.

Immune System

Temporal Dynamics of the Plasma Proteomic Landscape Reveals Maladaptation in ME/CFS Following Exertion.

Germain, Arnaud, Glass, Katherine A, Eckert, Melissa A et al.·Molecular & cellular proteomics : MCP·2025

Researchers studied what happens in the blood of ME/CFS patients during and after exercise to understand post-exertional malaise (PEM)—the worsening of symptoms that occurs after physical activity. They measured over 6,000 different proteins in 79 ME/CFS patients and 53 healthy controls before exercise, immediately after, and during recovery. They found that ME/CFS patients have abnormal protein changes during recovery that suggest their immune system and energy-producing cells are not working properly after exertion.

Immune SystemPost-Exertional Malaise

E2 ModerateCohortPEM requiredCross-Sectional

Autonomic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Findings from the Multi-Site Clinical Assessment of ME/CFS (MCAM) Study in the USA.

Issa, Anindita, Lin, Jin-Mann S, Chen, Yang et al.·Journal of clinical medicine·2025

This study found that people with ME/CFS experience much higher levels of autonomic nervous system problems—which control things like heart rate, blood pressure, and digestion—compared to healthy people. Nearly all ME/CFS patients (97%) had at least one autonomic symptom, with common complaints including dizziness, cold hands and feet, and difficulty standing up. The more autonomic symptoms someone had, especially in certain areas like blood pressure regulation and stomach problems, the more severe their overall illness tended to be.

Autonomic Nervous System

Understanding symptom clusters, diagnosis and healthcare experiences in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID: a cross-sectional survey in the UK.

Mansoubi, Maedeh, Richards, Thomas, Ainsworth-Wells, Martine et al.·BMJ open·2025

This large UK survey asked over 8,800 people with ME/CFS or long COVID about their symptoms and experiences with healthcare. The study found that fatigue, brain fog, pain, and sleep problems are the most common symptoms, but people often wait years for a diagnosis. Even after new healthcare guidelines were introduced, most patients said they weren't satisfied with the care they received from the NHS.

E2 ModerateCohortPEM not requiredCase-Control

Diagnosis of chronic fatigue syndrome using beat-to-beat autonomic measurements.

Kujawski, Sławomir, Tabisz, Hanna, Morten, Karl J et al.·Journal of translational medicine·2025

Researchers used artificial intelligence to analyze how the heart and nervous system behave differently in ME/CFS patients compared to healthy people. By measuring heart rate changes beat-by-beat, they found a pattern that could identify ME/CFS patients with 89% accuracy. The key differences included a less responsive vagal nerve (which normally calms the body), a more active stress response in blood vessels, and less efficient heart pumping.

Autonomic Nervous System

E2 ModerateCohortPEM requiredObservational

The Clinical Relevance of Mast Cell Activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Rohrhofer, Johanna, Ebner, Lilian, Schweighardt, Johannes et al.·Diagnostics (Basel, Switzerland)·2025

This study looked at whether mast cells—immune cells that release chemicals causing inflammation—play a role in ME/CFS. Researchers surveyed 687 ME/CFS patients and reviewed records from 383 others, finding that about 25% had signs of problematic mast cell activation. Importantly, patients with mast cell problems who received targeted treatment reported better symptom relief than those without mast cell involvement, suggesting this might be a treatable subtype of ME/CFS.

Immune SystemPost-Exertional Malaise

Autonomic Nervous SystemDiagnostics

The Diagnostic Journey of Dysautonomia Patients: Insights from a Patient-Reported Outcome Study.

O'Dell, John A, Walker, Ash, Latham, Andrew J et al.·Journal of patient experience·2025

This study followed 672 adults with dysautonomia (a condition where the nervous system that controls automatic body functions doesn't work properly) to understand how long it takes to get diagnosed and which doctors help with diagnosis. On average, it took 7.7 years for people to receive a diagnosis, and they often saw multiple types of doctors before getting answers. The study found that dysautonomia commonly occurs alongside other conditions like Ehlers-Danlos syndrome, mast cell disorders, and ME/CFS, which can make diagnosis even more confusing.

E2 ModerateCohortPEM unclearLongitudinal

Characterization of Post-Viral Infection Behaviors Among Patients With Long COVID: Prospective, Observational, Longitudinal Cohort Analyses of Fitbit Data and Patient-Reported Outcomes.

Zhang, Tianmai M, Sharp, Sydney P, Scott, John D et al.·JMIR formative research·2025

Researchers gave 82 people with long COVID or ME/CFS Fitbit devices to track their physical activity, heart rate, and sleep for up to a year, while also asking them to report how they felt. They found that people who were less physically active reported worse fatigue, breathing problems, and physical function, and their symptoms worsened over time compared to those who remained more active. This suggests that activity levels may be related to symptom severity in long COVID, though the study couldn't prove that low activity causes worse symptoms.

Sleep

E2 ModerateCohortPEM not requiredObservational

Nonpelvic comorbid symptoms of 45 patients with pain of pelvic venous origin, before and after treatment.

Smith, Steven J, Smith, B Holly, Sichlau, Michael J et al.·Phlebology·2025

This study looked at 45 women with chronic pelvic pain caused by abnormal blood pooling in pelvic veins. These patients experienced many symptoms beyond pelvic pain—including brain fog, fatigue, migraines, constipation, and anxiety. After receiving a catheter-based procedure to fix the blood pooling, most of these systemic symptoms improved significantly (by 50% or more).

Pain and SensitizationAutonomic Nervous SystemCognitive Impairment

HERV activation segregates ME/CFS from fibromyalgia while defining a novel nosologic entity.

Giménez-Orenga, Karen, Martín-Martínez, Eva, Nathanson, Lubov et al.·eLife·2025

This study looked at special genetic materials called human endogenous retroviruses (HERVs) in the blood cells of women with ME/CFS, fibromyalgia, both conditions, or neither. The researchers found that the pattern of which HERVs were active could perfectly distinguish between these four groups—suggesting this could become a reliable blood test to diagnose these conditions. The study also found that ME/CFS patients had specific changes in immune cells that matched how severe their symptoms were.

BiomarkersImmune System

Abnormal breathing patterns and hyperventilation are common in patients with chronic fatigue syndrome during exercise.

Mancini, Donna M, Brunjes, Danielle L, Cook, Dane et al.·Frontiers in medicine·2025

Researchers studied how patients with ME/CFS breathe during exercise and found that many breathe abnormally in ways that healthy people do not. Specifically, 42% of ME/CFS patients showed irregular breathing patterns, and 32% were breathing too fast and too deeply (hyperventilation). These breathing problems were much more common in ME/CFS patients than in the healthy control group, suggesting that abnormal breathing may be contributing to the fatigue and breathlessness patients experience.

E2 ModerateCohortPEM unclearObservational

Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort study.

Steen, Olivier D, Bos, Martje, van Ockenburg, Sonja L et al.·BMC medicine·2025

This study found that ME/CFS, fibromyalgia, and irritable bowel syndrome tend to run in families alongside conditions like depression, anxiety, autoimmune diseases, and metabolic disorders. Researchers analyzed data from over 166,000 people in a Dutch population cohort to understand whether these conditions share common inherited risk factors. The findings suggest that the causes of functional disorders like ME/CFS may overlap with the causes of immune and metabolic diseases, which could point to new treatment approaches.

Immune System