TGI Friday! Our regular round-up of recently published MECFS research abstracts and related items | 21 June 2013

June 21, 2013

From the Journal of Psychosomatic Research, 3 June 2013.

Differences in physical functioning between relatively active and passive patients with Chronic Fatigue Syndrome

Desirée C.W.M. Vos-Vromans, Ivan P.J. Huijnen, Albère J.A. Köke, Henk A.M. Seelen, et al.
Revant Rehabilitation Centre Breda, Brabantlaan 1, 4817 JW Breda, The Netherlands



According to the Cognitive behavioral therapy (CBT) protocol for patients with Chronic Fatigue Syndrome (CFS), therapists are advised to categorize patients in relatively active and passive patients. However, evidence to support the differences in physical functioning between these subgroups is limited. Using the baseline data from a multicentre randomized controlled trial (FatiGo), the differences in actual and perceived physical functioning between active and passive patients with CFS were evaluated.


Sixty patients, who received CBT during the FatiGo trial were included. Based on the expert opinion and using the definitions of subgroups defined in the CBT protocols, the therapist categorized the patient. Data from an activity monitor was used to calculate actual physical functioning, physical activity, daily uptime, activity fluctuations and duration of rest during daily life. Perceived physical functioning was assessed by measuring physical activity, physical functioning and functional impairment with the Checklist Individual Strength, Short Form-36 and Sickness-Impact Profile 8.


Relatively active patients have a significantly higher daily uptime and show significantly less fluctuations in activities between days. Passive patients experience a significantly lower level of physical functioning and feel more functionally impaired in their mobility. However, no significant differences were found in the other actual or perceived physical functioning indices.


A clear difference in actual and perceived physical functioning between relatively active and passive patients with CFS as judged by their therapists could not be found. Future research is needed to form a consensus on how to categorize subgroups of patients with CFS.

From the Journal of Clinical Rheumatology, 5 June 2013 [Epub ahead of print].

Cognitive performance is of clinical importance, but is unrelated to pain severity in women with chronic fatigue syndrome.

Ickmans K, Meeus M, Kos D, Clarys P, Meersdom G, Lambrecht L, Pattyn N, Nijs J.
Pain in Motion Research Group (PIM), Department of Human Physiology, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Building L, Pleinlaan 2, 1050, Brussels, Belgium.


In various chronic pain populations, decreased cognitive performance is known to be related to pain severity. Yet, this relationship has not been investigated in patients with chronic fatigue syndrome (CFS).

This study investigated the relationship between cognitive performance and (1) pain severity, (2) level of fatigue, and (3) self-reported symptoms and health status in women with CFS.

Examining the latter relationships is important for clinical practice, since people with CFS are often suspected to exaggerate their symptoms. A sample of 29 female CFS patients and 17 healthy controls aged 18 to 45 years filled out three questionnaires (Medical Outcomes Study 36-Item Short-Form Health Survey, Checklist Individual Strength (CIS), and CFS Symptom List) and performed three performance-based cognitive tests (psychomotor vigilance task, Stroop task, and operation span task), respectively.

In both groups, pain severity was not associated with cognitive performance. In CFS patients, the level of fatigue measured with the CFS Symptom List, but not with the CIS, was significantly correlated with sustained attention. Self-reported mental health was negatively correlated with all investigated cognitive domains in the CFS group.

These results provide evidence for the clinical importance of objectively measured cognitive problems in female CFS patients. Furthermore, a state-like measure (CFS Symptom List) appears to be superior over a trait-like measure (CIS) in representing cognitive fatigue in people with CFS.

Finally, the lack of a significant relationship between cognitive performance and self-reported pain severity suggests that pain in CFS might be unique.

From Frontiers in Physiology, 30 May 2013.

Multiscale analysis of heart rate variability in non-stationary environments

Jianbo Gao(1,2*), Brian M. Gurbaxani(3,*), Jing Hu(1), Keri J. Heilman(4), Vincent A. Emanuele II(3), Greg F. Lewis(4,5), Maria Davila(4), Elizabeth R. Unger(3) and Jin-Mann S. Lin(3,*)
1) PMB Intelligence LLC, West Lafayette, IN, USA
2) Mechanical and Materials Engineering, Wright State University, Dayton, OH, USA
3) Chronic Viral Diseases Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, USA
4) College of Medicine, Brain-Body Center, University of Illinois, Chicago, IL, USA
5) Research Triangle Institute, Raleigh, NC, USA


Heart rate variability (HRV) is highly non-stationary, even if no perturbing influences can be identified during the recording of the data. The non-stationarity becomes more profound when HRV data are measured in intrinsically non-stationary environments, such as social stress.

In general, HRV data measured in such situations are more difficult to analyze than those measured in constant environments.

In this paper, we analyze HRV data measured during a social stress test using two multiscale approaches, the adaptive fractal analysis (AFA) and scale-dependent Lyapunov exponent (SDLE), for the purpose of uncovering differences in HRV between chronic fatigue syndrome (CFS) patients and their matched-controls.

CFS is a debilitating, heterogeneous illness with no known biomarker. HRV has shown some promise recently as a non-invasive measure of subtle physiological disturbances and trauma that are otherwise difficult to assess. If the HRV in persons with CFS are significantly different from their healthy controls, then certain cardiac irregularities may constitute good candidate biomarkers for CFS.

Our multiscale analyses show that there are notable differences in HRV between CFS and their matched controls before a social stress test, but these differences seem to diminish during the test. These analyses illustrate that the two employed multiscale approaches could be useful for the analysis of HRV measured in various environments, both stationary and non-stationary.

From Comprehensive Psychiatry, 5 June 2013.

The role of neuroticism, perfectionism and depression in chronic fatigue syndrome. A structural equation modeling approach

Sergi Valero(a), Naia Sáez-Francàs(a), Natalia Calvo(a), José Alegre(b), Miquel Casas(c,a),
(a) Department of Psychiatry, Hospital Universitari Vall d’Hebron, CIBERSAM, Universitat Autònoma de Barcelona, Passeig de la Vall d’Hebron 119–129, 08035 Barcelona, Catalonia, Spain
(b) Department of Internal Medicine, Hospital Universitari Vall D´Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Passeig de la Vall d’Hebron 119–129, 08035 Barcelona, Catalonia, Spain
© Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Campus de Bellaterra s/n 08193, Bellaterra, Catalonia, Spain



Previous studies have reported consistent associations between Neuroticism, maladaptive perfectionism and depression with severity of fatigue in Chronic Fatigue Syndrome (CFS). Depression has been considered a mediator factor between maladaptive perfectionism and fatigue severity, but no studies have explored the role of neuroticism in a comparable theoretical framework. This study aims to examine for the first time, the role of neuroticism, maladaptive perfectionism and depression on the severity of CFS, analyzing several explanation models.


A sample of 229 CFS patients were studied comparing four structural equation models, testing the role of mediation effect of depression severity in the association of Neuroticism and/or Maladaptive perfectionism on fatigue severity.


The model considering depression severity as mediator factor between Neuroticism and fatigue severity is the only one of the explored models where all the structural modeling indexes have fitted satisfactorily (Chi square = 27.01, p = 0.079; RMSE = 0.047, CFI = 0.994; SRMR = 0.033). Neuroticism is associated with CFS by the mediation effect of depression severity. This personality variable constitutes a more consistent factor than maladaptive perfectionism in the conceptualization of CFS severity.


CFS, Chronic fatigue syndrome;
RMSE, Root Mean Squared Error;
CFI, Confirmatory Fit Index;
SRMR, Standardized Root Mean Residual;
FIS, Fatigue Impact Scale;
U-FIS, Unidimensional Fatigue Impact Scale;
ZKPQ, Zuckerman–Kuhlman Personality Questionnaire;
MPS-F, Frost Multidimensional Perfectionism Scale;
HADS, Hospital Anxiety–Depression Scale

From the
European Journal of Pediatrics
June 2013.

Clinical Practice: Chronic fatigue syndrome

Charlotte L. Werker, Sanne L. Nijhof, Elise M. van de Putte


The diagnosis chronic fatigue syndrome (CFS) was conceptualized in the mid-1980s. It is a clinically defined condition characterized by severe and disabling new onset fatigue with at least four additional symptoms: impaired memory or concentration, sore throat, tender cervical or axillary lymph nodes, muscle pain, multi-joint pain, new headaches, unrefreshing sleep or post-exertion malaise.

Chronic fatigue syndrome in adolescents is a rare condition compared to symptomatic fatigue. The estimated prevalence of adolescent CFS ranges between 0.11 and 1.29 % in Dutch, British, and US populations.

Diagnosis of the chronic fatigue syndrome is established through exclusion of other medical and psychiatric causes of chronic fatiguing illness. Taking a full clinical history and a full physical examination are therefore vital.

In adolescence, CFS is associated with considerable school absence with long-term detrimental effects on academic and social development. One of the most successful potential treatments for adolescents with CFS is cognitive behavioural therapy, which has been shown to be effective after 6 months in two thirds of the adolescents with CFS. This treatment effect sustains at 2–3-year follow-up.

In conclusion, the diagnosis CFS should be considered in any adolescent patient with severe disabling long-lasting fatigue. Cognitive behavioural therapy is effective in 60–70 % of the patients. Prompt diagnosis favours the prognosis.

From JAMA Psychiatry, 12 Junne 2013.

Autoimmune Diseases and Severe Infections as Risk Factors for Mood Disorders: A Nationwide Study

Michael E. Benros, MD; Berit L. Waltoft, MSc; Merete Nordentoft, DrMedSc; Søren D. Østergaard, MD; William W. Eaton, PhD; Jesper Krogh, nMD; Preben B. Mortensen, DrMedSc



Mood disorders frequently co-occur with medical diseases that involve inflammatory pathophysiologic mechanisms. Immune responses can affect the brain and might increase the risk of mood disorders, but longitudinal studies of comorbidity are lacking.


To estimate the effect of autoimmune diseases and infections on the risk of developing mood disorders.


Nationwide, population-based, prospective cohort study with 78 million person-years of follow-up. Data were analyzed with survival analysis techniques and adjusted for calendar year, age, and sex.

Individual data drawn from Danish longitudinal registers.


A total of 3.56 million people born between 1945 and 1996 were followed up from January 1, 1977, through December 31, 2010, with 91 637 people having hospital contacts for mood disorders.


The risk of a first lifetime diagnosis o mood disorder assigned by a psychiatrist in a hospital, outpatient clinic, or emergency department setting. Incidence rate ratios (IRRs) and accompanying 95% CIs are used as measures of relative risk.


A prior hospital contact because of autoimmune disease increased the risk of a subsequent mood disorder diagnosis by 45% (IRR, 1.45; 95% CI, 1.39-1.52). Any history of hospitalization for infection increased the risk of later mood disorders by 62% (IRR, 1.62; 95% CI, 1.60-1.64). The 2 risk factors interacted in synergy and increased the risk of subsequent mood disorders even further (IRR, 2.35; 95% CI, 2.25-2.46). The number of infections and autoimmune diseases increased the risk of mood disorders in a dose-response
relationship. Approximately one-third (32%) of the participants diagnosed as having a mood disorder had a previous hospital contact because of an infection, whereas 5% had a previous hospital contact
because of an autoimmune disease.


Autoimmune diseases and infections are risk factors for subsequent mood disorder diagnosis. These associations seem compatible with an immunologic hypothesis for the development of mood disorders in subgroups of patients.

From Biological Psychiatry, 9 June 2013 (E-published before print).

Psychobiotics: A Novel Class of Psychotropic

Timothy G. Dinan(*), Catherine Stanton, John F. Cryan
Alimentary Pharmabiotic Centre, University College Cork and
Teagasc Moorepark, Cork, Ireland

Here, we define a psychobiotic as a live organism that, when ingested in adequate amounts, produces a health benefit in patients suffering from psychiatric illness. As a class of probiotic, these bacteria are capable of producing and delivering neuroactive substances such as gamma-aminobutyric acid and serotonin, which act on the brain-gut axis.

Preclinical evaluation in rodents suggests that certain psychobiotics possess antidepressant or anxiolytic activity. Effects may be mediated via the vagus nerve, spinal cord, or neuroendocrine systems.

So far, psychobiotics have been most extensively studied in a liaison psychiatric setting in patients with irritable bowel syndrome, where positive benefits have been reported for a number of organisms including Bifidobacterium infantis.

Evidence is emerging of benefits in alleviating symptoms of depression and in chronic fatigue syndrome. Such benefits may be related to the anti-inflammatory actions of certain psychobiotics and a capacity to reduce hypothalamic-pituitary-adrenal axis activity. Results from large scale placebo-controlled studies are awaited.

From Biological Psychology, 12 June 2013.

Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome

Jana Strahler(a), Susanne Fischer(a), Urs M. Nater(a), Ulrike Ehlert(b), Jens Gaab(c).

a) Clinical Biopsychology, Department of Psychology, University of Marburg, Gutenbergstrasse 18, 35032 Marburg, Germany
b) Clinical Psychology and Psychotherapy, Institute of Psychology, University of Zurich, Binzmuehlestrasse 14, 8050 Zuerich, Switzerland
c) Clinical Psychology and Psychotherapy, Institute of Psychology, University of Basel, Missionsstrasse 62, 4055 Basel, Switzerland


• CFS patients showed diminished catecholaminergic responses to an exercise stressor.
• They showed unaltered catecholaminergic responses to a pharmacological stressor.
• Exercise seems to be an important stressor for CFS patients.
• Inadequate catecholaminergic responses to physical exertion might contribute to CFS symptoms.


Chronic fatigue syndrome (CFS) is characterized by fatigue lasting 6 months or longer. CFS has been associated with a disturbed (re-)activity of the autonomic nervous system. However, the sympathetic adrenomedulla (SAM) remains under-examined in CFS.

To investigate SAM reactivity, we implemented a submaximal cycle ergometry (ERGO) and a pharmacological test (Insulin Tolerance Test, ITT) in 21 CFS patients and 20 age-, sex-, and BMI-matched controls. Plasma norepinephrine and epinephrine were collected once before and twice after the tests (+10/+20, and +30 min). Lower baseline levels and attenuated responses of epinephrine to the ERGO were found in CFS patients compared to controls, while the groups did not differ in their responses to the ITT.

To conclude, we found evidence of altered sympathetic-neural and SAM reactivity in CFS. Exercise stress revealed a subtle catecholaminergic hyporeactivity in CFS patients. It is conceivable that inadequate catecholaminergic responses to physical exertion might contribute to CFS symptoms.

From the Journal of Disability and Rehabilitation, 4 June 2013.


Use of an online survey to explore positive and negative outcomes of rehabilitation for people with CFS/ME

Peter William Gladwell(1), Derek Pheby(2), Tristana Rodriguez(3), and Fiona Poland(4)
1) North Bristol NHS Trust, Bristol, UK,
2) Buckinghamshire New University, Society and Health, Uxbridge, UK,
3) Action for ME, Bristol, UK, and
4) Health and Society, University of East Anglia, Norwich, UK



First, to explore the experiences of people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) of rehabilitation therapies so as to build an understanding of reasons for the discrepancy between the notably mixed experiences regarding effectiveness reported in patient surveys and the RCT evidence about the efficacy of Graded Exercise Therapy (GET). GET is a form of structured and supervised activity management that aims for gradual but progressive increases in physical activity.

Second, to review patient experiences of two related rehabilitation approaches, Exercise on Prescription (EoP) and Graded Activity Therapy (GAT).


An online survey conducted by the charity Action for ME generated qualitative data about 76 patient experiences of rehabilitation undertaken during or after 2008, examined using thematic analysis.


Both positive and negative experiences of rehabilitation were reported. Positive themes included supportive communication, the benefits of a routine linked with baseline setting and pacing, the value of goal setting, and increasing confidence associated with exercise. Negative themes included poor communication, feeling pushed to exercise beyond a sustainable level, having no setback plan, and patients feeling blamed for rehabilitation not working.


The negative themes may help explain the negative outcomes from rehabilitation reported by previous patient surveys. The negative themes indicate rehabilitation processes which contradict the NICE (National Institute for Health and Clinical Excellence) Guideline advice regarding GET, indicating that some clinical encounters were not implementing these. These findings suggest areas for improving therapist training, and for developing quality criteria for rehabilitation in CFS/ME.

2 thoughts on “TGI Friday! Our regular round-up of recently published MECFS research abstracts and related items | 21 June 2013”

  1. You haven’t posted this paper which shows CoQ10 above 1200 mg works in other neuroimmune diseases and therefore should work in ME.

    Mol Neurobiol. 2013 Jun 13.

    Coenzyme Q10 Depletion in Medical and Neuropsychiatric Disorders: Potential Repercussions and Therapeutic Implications.

    Morris G, Anderson G, Berk M, Maes M.

    Coenzyme Q10 (CoQ10) is an antioxidant, a membrane stabilizer, and a vital cofactor in the mitochondrial electron transport chain, enabling the generation of adenosine triphosphate. It additionally regulates gene expression and apoptosis; is an essential cofactor of uncoupling proteins; and has anti-inflammatory, redox modulatory, and neuroprotective effects. This paper reviews the known physiological role of CoQ10 in cellular metabolism, cell death, differentiation and gene regulation, and examines the potential repercussions of CoQ10 depletion including its role in illnesses such as Parkinson’s disease, depression, myalgic encephalomyelitis/chronic fatigue syndrome, and fibromyalgia. CoQ10 depletion may play a role in the pathophysiology of these disorders by modulating cellular processes including hydrogen peroxide formation, gene regulation, cytoprotection, bioenegetic performance, and regulation of cellular metabolism. CoQ10 treatment improves quality of life in patients with Parkinson’s disease and may play a role in delaying the progression of that disorder. Administration of CoQ10 has antidepressive effects. CoQ10 treatment significantly reduces fatigue and improves ergonomic performance during exercise and thus may have potential in alleviating the exercise intolerance and exhaustion displayed by people with myalgic encepholamyletis/chronic fatigue syndrome. Administration of CoQ10 improves hyperalgesia and quality of life in patients with fibromyalgia. The evidence base for the effectiveness of treatment with CoQ10 may be explained via its ability to ameliorate oxidative stress and protect mitochondria.

  2. I did take Co-Q 10, daily in a high dose, for four months – it did no good whatsoever and actually made me much worse in general – it was like permanent “payback”.
    It was the more expensive ubiquinol version I tried.
    I believe, however, that it should be taken in conjunction with D-Ribose and perhaps some other supplements, for it to work properly. I simply couldn’t afford D-ribose as well as the correct form of Co-Q-10.

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