ME Association May Summary of ME/CFS Published Research | 07 June 2018

June 7, 2018


ME Association Index of Published ME/CFS Research

The Index of Published ME/CFS Research has now been updated to take account of the studies that have been published during May. It is free to download and comes with an interactive contents table.

This is an A-Z index of all the most important research studies (and selected key documents and articles), listed by subject matter, that have been published on ME/CFS and is correct to 31st May 2018.

You can also find the index in the Research section of our website.

The following is a list of research abstracts published in May 2018

Bileviciute-Ljungar I, et al. (2018)
Patients with chronic fatigue syndrome do not score higher on the autism-spectrum quotient than healthy controls: Comparison with autism spectrum disorder
Scandanavian Journal of Psychology [Epub ahead of print].


Clinically, there is an overlap of several symptoms of chronic fatigue syndrome (CFS) and autism spectrum disorder (ASD), including fatigue; brain “fog”; cognitive impairments; increased sensitivity to sound, light, and odour; increased pain and tenderness; and impaired emotional contact.

Adults with CFS (n = 59) or ASD (n = 50) and healthy controls (HC; n = 53) were assessed with the Autism-Spectrum Quotient (AQ) in a cross-sectional study. Non-parametric analysis was used to compare AQ scores among the groups. Univariate analysis of variance (ANCOVA) was used to identify if age, sex, or diagnostic group influenced the differences in scores.

Patients with ASD scored significantly higher on the AQ than the CFS group and the HC group. No differences in AQ scores were found between the CFS and HC groups. AQ results were influenced by the diagnostic group but not by age or sex, according to ANCOVA.

Despite clinical observations of symptom overlap between ASD and CFS, adult patients with CFS report few autistic traits in the self-report instrument, the AQ. The choice of instrument to assess autistic traits may influence the results.

Boissoneault J, et al. (2018)
Cerebral blood flow and heart rate variability predict fatigue severity in patients with chronic fatigue syndrome
Brain Imaging and Behavior.


Prolonged, disabling fatigue is the hallmark of chronic fatigue syndrome (CFS). Previous neuroimaging studies have provided evidence for nervous system involvement in CFS etiology, including perturbations in brain structure/function.

In this arterial spin labeling (ASL) MRI study, we examined variability in cerebral blood flow (CBFV) and heart rate (HRV) in 28 women: 14 with CFS and 14 healthy controls. We hypothesized that CBFV would be reduced in individuals with CFS compared to healthy controls, and that increased CBFV and HRV would be associated with lower levels of fatigue in affected individuals.

Our results provided support for these hypotheses. Although no group differences in CBFV or HRV were detected, greater CBFV and more HRV power were both associated with lower fatigue symptom severity in individuals with CFS.

Exploratory statistical analyses suggested that protective effects of high CBFV were greatest in individuals with low HRV. We also found novel evidence of bidirectional association between the very high frequency (VHF) band of HRV and CBFV.

Taken together, the results of this study suggest that CBFV and HRV are potentially important measures of adaptive capacity in chronic illnesses like CFS. Future studies should address these measures as potential therapeutic targets to improve outcomes and reduce symptom severity in individuals with CFS.

Castro-Marrero J, et al. (2018)
Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis
Journal of Sleep Research [Epub ahead of print].


Non-restorative sleep is a hallmark symptom of chronic fatigue syndrome/myalgic encephalomyelitis. However, little is known about self-reported sleep disturbances in these subjects.

This study aimed to assess the self-reported sleep quality and its impact on quality of life in a Spanish community-based chronic fatigue syndrome/myalgic encephalomyelitis cohort.

A prospective cross-sectional cohort study was conducted in 1,455 Spanish chronic fatigue syndrome/myalgic encephalomyelitis patients. Sleep quality, fatigue, pain, functional capacity impairment, psychopathological status, anxiety/depression and health-related quality of life were assessed using validated subjective measures.

The frequencies of muscular, cognitive, neurological, autonomic and immunological symptom clusters were above 80%. High scores were recorded for pain, fatigue, psychopathological status, anxiety/depression, and low scores for functional capacity and quality of life, all of which correlated significantly (all p < 0.01) with quality of sleep as measured by the Pittsburgh Sleep Quality Index.

Multivariate regression analysis showed that after adjusting for age and gender, the pain intensity (odds ratio, 1.11; p <0.05), psychopathological status (odds ratio, 1.85; p < 0.001), fibromyalgia (odds ratio, 1.39; p < 0.05), severe autonomic dysfunction (odds ratio, 1.72; p < 0.05), poor functional capacity (odds ratio, 0.98; p < 0.05) and quality of life (odds ratio, 0.96; both p < 0.001) were significantly associated with poor sleep quality.

These findings suggest that this large chronic fatigue syndrome/myalgic encephalomyelitis sample presents poor sleep quality, as assessed by the Pittsburgh Sleep Quality Index, and that this poor sleep quality is associated with many aspects of quality of life.

Rivas JL, et al. (2018)
Association of T and NK Cell Phenotype with the Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Frontiers in Immunology.


Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a pathological condition characterized by incapacitating fatigue and a combination of neurologic, immunologic, and endocrine symptoms. At present its diagnosis is based exclusively on clinical criteria.

Several studies have described altered immunologic profiles; therefore, we proposed to further examine the more significant differences, particularly T and NK cell subpopulations that could be conditioned by viral infections, to discern their utility in improving the diagnosis and characterization of the patients.

The study included 76 patients that fulfilled the revised Canadian Consensus Criteria (CCC 2010) for ME/CFS and 73 healthy controls, matched for age and gender. Immunophenotyping of different T cell and natural killer cell subpopulations in peripheral blood was determined by flow cytometry.

ME/CFS patients showed significantly lower values of T regulatory cells (CD4+CD25++(high) FOXP3+) and higher NKT-like cells (CD3+CD16+/−CD56+) than the healthy individuals.

Regarding NK phenotypes, NKG2C was significantly lower and NKCD69 and NKCD56 bright were significantly higher in the patients group.

A classification model was generated using the more relevant cell phenotype differences (NKG2C and T regulatory cells) that was able to classify the individuals as ME/CFS patients or healthy in a 70% of cases.

The observed differences in some of the subpopulations of T and NK cells between patients and healthy controls could define a distinct immunological profile that can help in the diagnostic process of ME/CFS patients, contribute to the recognition of the disease and to the search of more specific treatments. However, more studies are needed to corroborate these findings and to contribute to establish a consensus in diagnosis.

Roerink ME, et al. (2018)
Hair and salivary cortisol in a cohort of women with chronic fatigue syndrome
Hormones and Behaviour [Epub ahead of Print].


Hypocortisolism has been found in CFS patients in blood, urine, and saliva. It is unclear if hypocortisolism can also be demonstrated using long-term cortisol measurements, such as cortisol in hair. In addition, the interaction between the HPA axis and the immune system, both expected to play an important role in CFS, is unclear.

The objective of the current study was to compare hair and salivary cortisol concentrations in a cohort of female CFS patients to those in healthy controls, and to test the effect of an interleukin-1 receptor antagonist (anakinra) on the HPA axis.

Salivary cortisol concentrations of 107 CFS patients were compared to 59 healthy controls, with CFS patients showing a decreased cortisol awakening response (4.2 nmol/L ± 5.4 vs 6.1 nmol/L ± 6.3, p = 0.036).

Total cortisol output during the day did not differ significantly in saliva, but there was a trend to lower hair cortisol in a subset of 46 patients compared to 46 controls (3.8 pg/mg ± 2.1 vs 4.3 pg/mg ± 1.8, p = 0.062).

After four weeks of treatment with either daily anakinra (100 mg/day) or placebo, there was a slight decrease of hair cortisol concentrations in the anakinra group compared to an increase in the placebo group (p = 0.022).

This study confirms the altered dynamics of the HPA axis in a group of CFS patients, and for the first time shows that this might also be present for long-term cortisol measures.

Sevel LS, et al. (2018)
Structural brain changes versus self-report: machine-learning classification of chronic fatigue syndrome patients
Experimental Brain Research [Epub ahead of print]


Chronic fatigue syndrome (CFS) is a disorder associated with fatigue, pain, and structural/functional abnormalities seen during magnetic resonance brain imaging (MRI). Therefore, we evaluated the performance of structural MRI (sMRI) abnormalities in the classification of CFS patients versus healthy controls and compared it to machine learning (ML) classification based upon self-report (SR).

Participants included 18 CFS patients and 15 healthy controls (HC). All subjects underwent T1-weighted sMRI and provided visual analogue-scale ratings of fatigue, pain intensity, anxiety, depression, anger, and sleep quality.

sMRI data were segmented using FreeSurfer and 61 regions based on functional and structural abnormalities previously reported in patients with CFS. Classification was performed in RapidMiner using a linear support vector machine and bootstrap optimism correction.

We compared ML classifiers based on (1) 61 a priori sMRI regional estimates and (2) SR ratings. The sMRI model achieved 79.58% classification accuracy. The SR (accuracy = 95.95%) outperformed both sMRI models. Estimates from multiple brain areas related to cognition, emotion, and memory contributed strongly to group classification.

This is the first ML-based group classification of CFS. Our findings suggest that sMRI abnormalities are useful for discriminating CFS patients from HC, but SR ratings remain most effective in classification tasks.

Teodoro T, et al. (2018)
A unifying theory for cognitive abnormalities in functional neurological disorders, fibromyalgia and chronic fatigue syndrome: systematic review
Journal of Neurology, Neurosurgery and Psychiatry [Epub ahead of print].


Background: Functional cognitive disorder (FCD) describes cognitive dysfunction in the absence of an organic cause. It is increasingly prevalent in healthcare settings, yet its key neuropsychological features have not been reported in large patient cohorts. We hypothesised that cognitive profiles in fibromyalgia (FM), chronic fatigue syndrome (CFS) and functional neurological disorders (FNDs) would provide a template for characterising FCD.

Methods: We conducted a systematic review of studies with cognition-related outcomes in FM, CFS and FND.

Results: We selected 52 studies on FM, 95 on CFS and 39 on FND. We found a general discordance between high rates of subjective cognitive symptoms, including forgetfulness, distractibility and word-finding difficulties, and inconsistent objective neuropsychological deficits.

Objective deficits were reported, including poor selective and divided attention, slow information processing and vulnerability to distraction. In some studies, cognitive performance was inversely correlated with pain, exertion and fatigue. Performance validity testing demonstrated poor effort in only a minority of subjects, and patients with CFS showed a heightened perception of effort.

Discussion: The cognitive profiles of FM, CFS and non-cognitive FND are similar to the proposed features of FCD, suggesting common mechanistic underpinnings. Similar findings have been reported in patients with mild traumatic brain injury and whiplash.

We hypothesise that pain, fatigue and excessive interoceptive monitoring produce a decrease in externally directed attention. This increases susceptibility to distraction and slows information processing, interfering with cognitive function, in particular multitasking.

Routine cognitive processes are experienced as unduly effortful. This may reflect a switch from an automatic to a less efficient controlled or explicit cognitive mode, a mechanism that has also been proposed for impaired motor control in FND.

These experiences might then be overinterpreted due to memory perfectionism and heightened self-monitoring of cognitive performance.

Twisk F (2018)
Dutch Health Council Advisory Report on Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: Taking the Wrong Turn
Diagnostics 8 (2).


Recently, the Dutch Health Council published their advisory report on Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) which is meant to determine the medical policy with regard to ME in the Netherlands.

The Health Council briefly discusses several diagnostic criteria and proposes to use new diagnostic criteria for “ME/CFS” in research and clinical practice in the future. The advisory report then summarizes organic abnormalities observed in the last decades and concludes that “ME/CFS” is a “serious, chronic, multisystem disease”.

According to the Health Council there are no curative treatments for “ME/CFS”, due to lack of knowledge, but specific medication could bring symptomatic relief. The Health Council recommends conducting more research, to (re)educate medical professionals about “ME/CFS”, to appoint three academic expertise centres, which will install a care network for patients, and to fairly judge the limitations (disability) of patients when they apply for a disability income, medical aid and care.

The advisory report was welcomed by many patients, because it puts an end to the dominance of the (bio)psychosocial explanatory model and seems to offer a perspective of improving the situation of patients. However, the starting point of the advisory report, a new definition of “ME/CFS”, will have serious (long-lasting) consequences for patients and researchers.

Zinn MA, et al. (2018)
Cortical Hypoactivation During Resting EEG Suggests Central Nervous System Pathology in Patients with Chronic Fatigue Syndrome
Biological Psychology [Epub ahead or print].


We investigated cognitive impairment to executive function in 50 patients with chronic fatigue syndrome (CFS) and 50 matched healthy controls (HC).

Resting state EEG was collected from 19 scalp locations during a 3 minute, eyes-closed condition. Current densities were localized using exact low-resolution electromagnetic tomography (eLORETA).

The Multidimensional Fatigue Inventory (MFI-20) and the Fatigue Severity Scale (FSS) were administered to all participants. Independent t-tests and linear regression analyses were used to evaluate group differences in current densities, followed by statistical non-parametric mapping (SnPM) correction procedures.

Significant differences were found in the delta (1-3 Hz) and beta-2 (19-21 Hz) frequency bands. Delta sources were found predominately in the frontal lobe, while beta-2 sources were found in the medial and superior parietal lobe. Left-lateralized, frontal delta sources were associated with a clinical reduction in motivation.

The implications of abnormal cortical sources in patients with CFS are discussed.

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