The ME Association End of Week Research Round-up

June 26, 2020

Charlotte Stephens, Research Correspondent, ME Association.

We show below brief summaries of the research studies about ME/CFS that have been published in the last week, followed by the abstracts from those studies.

All research relating to ME/CFS can be located in the Index of ME/CFS Published Research which is updated at the end of every month and can be downloaded for free.

It is an A-Z of the most important published research studies and selected key documents and articles, listed by subject matter, on myalgic encephalomyelitis and/or chronic fatigue syndrome (ME/CFS).

You can use it to easily locate and read any research in a particular area that you might be interested in, e.g. epidemiology, infection, neurology, post-exertional malaise etc.

You can also find the Research Index in the Research section of the website together with a list of Research Summaries from the ME Association that provide lay explanations of the more important and interesting work that has been published to date.

ME/CFS Research Published 19th – 25th June 2020

This week, 5 new research studies have been published, highlights include:

  • Researchers from France identified some epidemiological and clinical features which were positively associated with PEM (Post-exertional malaise) severity in subsets of ME/CFS patients, such as age at disease onset and recurrent infections during the illness.
  • A research group from America looked into the relation between disease burden and research funding in the USA for ME/CFS. They found that the disease burden of ME/CFS is double that of HIV/AIDS and over half that of breast cancer.
    Furthermore, ME/CFS is more underfunded with respect to burden than any disease in NIH's analysis of funding and disease burden, with ME/CFS receiving roughly 7% of that in proportion with disease burden.
    They concluded that in order to be in proportion with disease burden, NIH funding for ME/CFS research would need to increase roughly 14-fold.
  • Belgium researchers found serum levels of Brain-derived neurotrophic factor (BDNF) were higher in patients with CFS and comorbid fibromyalgia compared to healthy controls.
    They concluded that altered BDNF might represent a key mechanism explaining CFS/FM pathophysiology.

ME/CFS Research references and abstracts

1. De Venter M et al. (2020)
The Relationship Between Childhood Trauma and the Response to Group Cognitive-Behavioural Therapy for Chronic Fatigue Syndrome.
Frontiers in Psychiatry 11: 563.

Objective: To examine the relationship between childhood trauma and the response to group cognitive-behavioural therapy (GCBT) for chronic fatigue syndrome (CFS).

Methods: A single cohort study conducted in an outpatient university referral center for CFS including a well-documented sample of adult patients meeting the CDC criteria for CFS and having received 9 to 12 months of GCBT. A mixed effect model was adopted to examine the impact of childhood trauma on the treatment response in general and over time.

The main outcome measures were changes in fatigue, as assessed with the Checklist Individual Strength (total score), and physical functioning, as gauged with the Short Form 36 Health Survey subscale, with the scales being completed at baseline, immediately after treatment completion and after 1 year.

Results: We included 105 patients with CFS. Childhood trauma was not significantly associated with the response to GCBT over time on level of fatigue or physical functioning.

Conclusion: Childhood trauma does not seem to have an effect on the treatment response to dedicated GCBT for CFS sufferers over time. Therefore, in the allocation of patients to this kind of treatment, a history of childhood trauma should not be seen as prohibitive.

2. Ghali A et al. (2020)
Epidemiological and Clinical Factors Associated With Post-Exertional Malaise Severity in Patients With Myalgic encephalomyelitis/chronic Fatigue Syndrome.
Journal of Translational Medicine 18 (1): 246.

Background: Post-exertional malaise (PEM), the cardinal feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), occurs generally after exposure to a stressor.

It is characterized by the worsening of ME/CFS symptoms and results in aggravating the course of the disease and the quality of life of patients.

Due to its unpredictable onset, severity, and recovery time, identifying patients with higher risk for severe PEM would allow preventing or reducing its occurrence. We thus aimed at defining possible factors that could be associated with PEM severity.

Methods: Adult patients fulfilling ME international consensus criteria who attended the internal medicine department of University hospital Angers-France between October 2011 and December 2019 were included retrospectively.

All patients were systematically hospitalized for an etiological workup and overall assessment. We reviewed their medical records for data related to the assessment: epidemiological data, fatigue features, clinical manifestations, and ME/CFS precipitants.

PEM severity was appreciated by the Center for Disease Control self-reported questionnaire. The study population was classified into quartiles according to PEM severity scores. Analyses were performed with ordinal logistic regression to compare quartile groups.

Results: 197 patients were included. PEM severity was found to be positively associated with age at disease onset ≥ 32 years (OR 1.8 [95% CI 1.1-3.0] (p = 0.03)), recurrent infections during the course of the disease (OR 2.1 [95% CI 1.2-3.7] (p = 0.009)), and when ME/CFS was elicited by a gastrointestinal infectious precipitant (OR 5.7 [1.7-19.3] (p = 0.006)).

Conclusion: We identified some epidemiological and clinical features, which were positively associated with PEM severity in subsets of ME/CFS patients. This could help improving disease management and patients' quality of life.

3. Keynejad R. et al. (2020)
Attentional processing and interpretative bias in functional neurological disorder.
Journal of Biobehavioral Medicine [Epub ahead of print].

Objective: Altered attentional processing (automatically attending to negative or illness-relevant information) and interpretative biases (interpreting ambiguous information as negative or illness-relevant) may be mechanistically involved in functional neurological disorder (FND). Common mechanisms between FND and chronic fatigue syndrome (CFS) have been proposed but not compared experimentally.

Methods: We compared cognitive task performance of FND, CFS and healthy control (HC) groups. Tasks assessed attentional bias towards illness-relevant stimuli (visual probe task), attentional control (attention network task) and somatic interpretations (interpretative bias task), alongside self-reported depression, anxiety, fatigue and general health.

Results: Thirty-seven participants diagnosed with FND, 52 participants diagnosed with CFS and 51 HC participants were included. Whilst participants with CFS showed attentional bias for illness-relevant stimuli relative to HC (t = -3.13 p = 0.002, d = 0.624), individuals with FND did not (t = -1.59, p = 0.118, d = 0.379). Both FND (t = 3.08, p = 0.003, d = 0.759) and CFS (t = 2.74, p = 0.007, d = 0.548) groups displayed worse attentional control than HC. Similarly, FND (t = 3.63, p < 0.001, d = 0.801) and CFS groups (t = 4.58, p < 0.001, d = 0.909) showed more somatic interpretative bias than HC.

Conclusions: Similar attentional control deficits and somatic interpretative bias in individuals with FND and CFS support potential shared mechanisms underlying symptoms. Interpretative bias towards somatic and illness-relevant stimuli in functional disorders may prove a therapeutic target.

4. Mirin A et al. (2020)
Research Update: The Relation Between ME/CFS Disease Burden and Research Funding in the USA.
Work [Epub ahead of print].

Background: Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is a debilitating, chronic, multisystem disease that affects an estimated 1 to 2.5 million Americans. It has no widely accepted biomarkers and no FDA-approved treatment. ME/CFS has traditionally been one of the lowest funded diseases by the United States National Institutes of Health (NIH).

Objectives: We provide here an update to our 2016 article, which estimated the disease burden of ME/CFS in the United States in 2013 and its relation to NIH's 2015 analysis of research funding and disease burden. This update incorporates more recent burden data from 2015 and funding data from 2017.

Methods: We perform a regression analysis on funding versus disease burden to determine 2017 funding levels that would be commensurate with burden. Burden figures for 2017 are estimated using population-based extrapolations of earlier data.

Results: We find the disease burden of ME/CFS is double that of HIV/AIDS and over half that of breast cancer. We also find that ME/CFS is more underfunded with respect to burden than any disease in NIH's analysis of funding and disease burden, with ME/CFS receiving roughly 7% of that commensurate with disease burden.

Conclusions: To be commensurate with disease burden, NIH funding would need to increase roughly 14-fold.

5. Polli A et al. (2020)
DNA Methylation and BDNF Expression Account for Symptoms and Widespread Hyperalgesia in Patients With Chronic Fatigue Syndrome and Fibromyalgia.
Arthritis Rheumatology [Epub ahead of print].

Background: Epigenetics of neurotrophic factors holds the potential to unravel the mechanisms underlying the pathophysiology of complex conditions such as chronic fatigue syndrome (CFS). This study explored the role of brain-derived neurotrophic factor (BDNF) genetics, epigenetics, and protein expression in patients with both CFS and comorbid fibromyalgia (CFS/FM).

Methods: A repeated-measures study in 54 participants (28 patients with CFS/FM and 26 matched healthy controls) was conducted. Participants underwent a comprehensive assessment, including questionnaires, sensory testing, and blood withdrawal. BDNF protein level was measured in serum (sBDNF) using ELISA, while polymorphism and DNA methylation were measured in blood, using pyrosequencing technology. To assess temporal stability of the measures, participants underwent the same assessment twice within four days.

Results: Repeated-measures mixed linear models were performed for between-group analysis. sBNDF was higher in patients with CFS/FM (F=15.703; mean difference: 3.31 ng/ml, 95% C.I. 1.65 to 4.96; p=.001), whereas BDNF DNA methylation was lower in Exon IX (F=9.312; mean difference -2.38%, C.I. -3.93 to -0.83; p=.003). BDNF DNA methylation was mediated by the Val66Met (rs6265) polymorphism. Lower methylation in the same region predicted higher sBDNF (F=4.910, t= -2.216, p=.029, 95% C.I. = -.712 to -.039) which in turn predicted participants' symptoms (F=14.410, t= 3.796, 95% C.I.= 1.79 to 5.71, p=.001) and widespread hyperalgesia (F=4.147, t= 2.036, 95% C.I.= .01 to .08, p=.044).

Discussion: sBDNF is higher in patients with CFS/FM and BDNF methylation in exon IX accounts for regulating protein expression. Altered BDNF might represent a key mechanism explaining CFS/FM pathophysiology.

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