The ME Association End of Week Research Round-up and ME/CFS Research Index | 29 February 2020

March 3, 2020

Charlotte Stephens, Research Correspondent, ME Association.

We show below five new research studies and abstracts published on ME/CFS in the final week of February, together with simple summaries that we hope you might find helpful.

  • In our last Round-up, we featured nine new research studies including from Dr Elisa Oltra and her team in Spain who received grant funding from the MEA Ramsay Research Fund to examine ME Biobank samples from severely affected patients.

The Index of Published ME/CFS Research

All the research published in February has now been included in the central Index of Published ME/CFS Research.

This is a convenient way to locate and read all the most recent and past studies by subject matter and author with links to PubMed or the relevant journal.

The Index is free to download, comes with an interactive contents table and carries an A-Z list of all the most important studies (and selected key documents, articles and parliamentary debates etc.).

You can also find the 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 15th – 28th February 2020

This last week, 5 new research studies have been published, including:

  • A review looking into the association of CFS with sleep disorders. The researchers concluded that sleep disorders in CFS patients are comorbid, rather than having a causal relationship.
  • Two studies on prevalence – one finding an average prevalence of 0.9% (using the CDC-1994 criteria for ME/CFS) amongst the research literature and the other reporting a prevalence of 6% for chronic fatigue amongst a randomly selected Danish general population sample of 7493 people.

ME/CFS Research – References and Abstracts

1. Gupta A, Deka R and Gupta S (2020)
A Critical Review to Investigate Chronic Fatigue Syndrome as Sleep Disorder
E-Cronicon 12 (1).

Introduction: Chronic fatigue syndrome is associated with marked fatigue and sleep disturbance specifically the non-restorative sleep. This has led to a though process among the Scientists to rule out possibility of association of CFS with Sleep Disorders. Researchers have tried to investigate the causal relationship between the two by virtue of multiple experiments, however consensus on the same still lacks.

Methods and Results: In current review, critical analysis of individual studies was conducted evaluating credibility of experiments leading to a final opinion pertaining to Chronic Fatigue Syndrome association with Sleep Pathology. Possible overlaps among different mechanisms were also identified to provide robust conclusion. 

Conclusion: Current review suggests that Chronic Fatigue Syndrome and Sleep Disorders can be more of comorbid rather than having a causal relationship. Hence there is a mix type of evidence which tries to build relationship between the two but definite conclusion clearly demonstrating CFS as a sleep disorder cannot be reached.

2. Lim EJ et al. (2020)
Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).
Journal of Translational Medicine 28 (1): 100.  

Background: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has been emerging as a significant health issue worldwide. This study aimed to systemically assess the prevalence of CFS/ME in various aspects of analyses for precise assessment.

Methods: We systematically searched prevalence of CFS/ME from public databases from 1980 to December 2018. Data were extracted according to 7 categories for analysis: study participants, gender and age of the participants, case definition, diagnostic method, publication year, and country of the study conducted. Prevalence data were collected and counted individually for studies adopted various case definitions. We analyzed and estimated prevalence rates in various angles: average prevalence, pooled prevalence and meta-analysis of all studies.

Results: A total of 1291 articles were initially identified, and 45 articles (46 studies, 56 prevalence data) were selected for this study. Total 1085,976 participants were enrolled from community-based survey (540,901) and primary care sites (545,075). The total average prevalence was 1.40 ± 1.57%, pooled prevalence 0.39%, and meta-analysis 0.68% [95% CI 0.48-0.97]. The prevalence rates were varied by enrolled participants (gender, study participants, and population group), case definitions and diagnostic methods. For example, in the meta-analysis; women (1.36% [95% CI 0.48-0.97]) vs. men (0.86% [95% CI 0.48-0.97]), community-based samples (0.76% [95% CI 0.53-1.10]) vs. primary care sites (0.63% [95% CI 0.37-1.10]), adults ≥ 18 years (0.65% [95% CI 0.43-0.99]) vs. children and adolescents < 18 years (0.55% [95% CI 0.22-1.35]), CDC-1994 (0.89% [95% CI 0.60-1.33]) vs. Holmes (0.17% [95% CI 0.06-0.49]), and interviews (1.14% [95% CI 0.76-1.72]) vs. physician diagnosis (0.09% [95% CI 0.05-0.13]), respectively.

Conclusions: This study comprehensively estimated the prevalence of CFS/ME; 0.89% according to the most commonly used case definition CDC-1994, with women approximately 1.5 to 2 folds higher than men in all categories. However, we observed the prevalence rates are widely varied particularly by case definitions and diagnostic methods. An objective diagnostic tool is urgently required for rigorous assessment of the prevalence of CFS/ME.

3. Ovejero et al. (2020)
Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients.
International Journal of Molecular Sciences 21 (4).

Advancements in nucleic acid sequencing technology combined with an unprecedented availability of metadata have revealed that 45% of the human genome constituted by transposable elements (TEs) is not only transcriptionally active but also physiologically necessary.

Dysregulation of TEs, including human retroviral endogenous sequences (HERVs) has been shown to associate with several neurologic and autoimmune diseases, including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, no study has yet addressed whether abnormal expression of these sequences correlates with fibromyalgia (FM), a disease frequently comorbid with ME/CFS.

The work presented here shows, for the first time, that, in fact, HERVs of the H, K and W types are overexpressed in immune cells of FM patients with or without comorbid ME/CFS. Patients with increased HERV expression (N = 14) presented increased levels of interferon (INF-β and INF-γ) but unchanged levels of TNF-α.

The findings reported in this study could explain the flu-like symptoms FM patients present with in clinical practice, in the absence of concomitant infections. Future work aimed at identifying specific genomic loci differentially affected in FM and/or ME/CFS is warranted.

4. Petersen MW et al. (2020)
Irritable bowel, chronic widespread pain, chronic fatigue and related syndromes are prevalent and highly overlapping in the general population: DanFunD.
Scientific Reports 10 (1): 3273.

Prevalence of functional somatic syndromes (FSS) in the general population varies with observed overlap between syndromes. However, studies including a range of FSS are sparse. We investigated prevalence and characteristics of various FSS and the unifying diagnostic construct bodily distress syndrome (BDS), and identified mutual overlap of the FSS and their overlap with BDS.

We included a stratified subsample of 1590 adults from a randomly selected Danish general population sample (n = 7493). Telephonic diagnostic interviews performed by three trained physicians were used to identify individuals with FSS and BDS.

Prevalence of overall FSS was 9.3%; 3.8% for irritable bowel, 2.2% for chronic widespread pain, 6.1% for chronic fatigue, 1.5% for whiplash associated disorders, and 0.9% for multiple chemical sensitivity. Prevalence of BDS was 10.7% where 2.0% had the multi-organ type. FSS were highly overlapping with low likelihood of having a “pure” type. Diagnostic agreement of FSS and BDS was 92.0%. Multi-syndromatic FSS and multi-organ BDS were associated with female sex, poor health, physical limitations, and comorbidity.

FSS are highly prevalent and overlapping, and multi-syndromatic cases are most affected. BDS captured the majority of FSS and may improve clinical management, making the distinction between multi- and mono-syndromatic patients easier.

5. Ying-Chih C et al. (2020)
Heart rate variability in patients with somatic symptom disorders and functional somatic syndromes: A systematic review and meta-analysis.
Neuroscience and Biobehavioural Reviews [Epub ahead of print].

This research is aimed to systematically review heart rate variability (HRV) findings of functional somatic syndromes (FSSs) and somatic symptom disorders (SSDs), and to compare the HRV values between FSSs/SSDs patients and healthy individuals. We included clinical studies assessing HRV (including baseline HRV and HRV reactivity) in FSSs/SSDs and healthy participants. We searched PubMed, Embase, PsycINFO, MEDLINE, and Web of Science databases from the earliest available date to June 2019.

Eighty-five studies comprising 3242 FSSs/SSDs patients and 2321 controls were included in the main meta-analysis; the baseline HRV value was significantly lower compared to healthy individuals (Hedges'g, -0.43; 95 % CI, -0.54 to -0.30; p < .001), with the largest effect size in fibromyalgia patients. A significant lower HRV was also found for total variability (Hedges'g, -0.56; 95 % CI, -0.77 to -0.36) and specific parasympathetic indices (Hedges'g, -0.41, 95 % CI; -0.54 to -0.30). HRV reactivity was significantly lower in FSSs/SSDs patients (Hedges'g, -0.42; 95 % CI, -0.64 to -0.20).

Our results support the notion that FSSs/SSDs patients have significantly lower HRV than healthy individuals.

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