TGI Good Friday! Our weekly round-up of recently published research abstracts | 3 April 2015

April 3, 2015

From Molecular Psychiatry, 32 March 2015.

Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome

M Hornig, G Gottschalk, D L Peterson, K K Knox, A F Schultz, M L Eddy, X Che and W I Lipkin


Myalgic encephalomyelitis/chronic fatigue syndrome is an unexplained debilitating disorder that is frequently associated with cognitive and motor dysfunction.

We analyzed cerebrospinal fluid from 32 cases, 40 subjects with multiple sclerosis and 19 normal subjects frequency-matched for age and sex using a 51-plex cytokine assay.

Group-specific differences were found for the majority of analytes with an increase in cases of CCL11 (eotaxin), a chemokine involved in eosinophil recruitment. Network analysis revealed an inverse relationship between interleukin 1 receptor antagonist and colony-stimulating factor 1, colony-stimulating factor 2 and interleukin 17F, without effects on interleukin 1α or interleukin 1β, suggesting a disturbance in interleukin 1 signaling.

Our results indicate a markedly disturbed immune signature in the cerebrospinal fluid of cases that is consistent with immune activation in the central nervous system, and a shift toward an allergic or T helper type-2 pattern associated with autoimmunity.

From Health Promotion and Chronic Disease Prevention in Canada, March 2015

Chronic fatigue syndrome and fibromyalgia in Canada: prevalence and associations with six health status indicators.

C Rusu(1), ME Gee(1), C Lagace(1,*), M Parlor(2)
1) Centre for Chronic Disease Prevention, Public Health Agency of Canada, Ottawa, Ontario, Canada.
2) National ME/FM Action Network, Nepean, Ontario, Canada.
* Correspondence: Claudia Lagace, Centre for Public Health Infrastructure, Public Health Agency of Canada, 120 Colonnade Road, A.L. 6701A, Ottawa, ON K1A 0K9; Tel: 418-842-2685; Fax: 613-960-3966; Email:



Few studies have considered the factors independently associated with chronic fatigue syndrome (CFS) and/or fibromyalgia (FM) or considered
the impact of these conditions on health status using population-based data.


We used data from the nationally representative 2010 Canadian Community Health Survey (n = 59 101) to describe self-reported health professional-diagnosed CFS and/or FM, and their associations with 6 health status indicators.


In 2010, diagnosed CFS and FM are reported by 1.4% (95% confidence interval [CI]: 1.3%-1.6%) and 1.5% (1.4%-1.7%), respectively, of the Canadian household population aged 12 years and over, with comorbid CFS and FM affecting 0.3% (0.3%-0.4%) of that population. Prevalent CFS and/or FM were more common among women, adults aged 40 years and over, those with lowest income, and those with certain risk factors for chronic disease (i.e. obesity, physical inactivity and smoking).

After controlling for differences between the groups, people with CFS and/or FM reported poorer health status than those with neither
condition on 5 indicators of health status, but not on the measure of fair/poor mental health. Having both CFS and FM and having multiple
comorbid conditions was associated with poorer health status.


Co-occurrence of CFS and FM and having other chronic conditions were strongly related to poorer health status and accounted for much of the
differences in health status. Understanding factors contributing to improved quality of life in people with CFS and/or FM, particularly in
those with both conditions and other comorbidities, may be an important area for future research.

From Qualitative Health Research, 26 February 2015 (epublished before print)

The Nature of Fatigue in Chronic Fatigue Syndrome

Karin Olson(1), Oksana Zimka(1), Eleanor Stein(2)
1) University of Alberta, Edmonton, Alberta, Canada
2) University of Calgary, Calgary, Alberta, Canada
Karin Olson, University of Alberta Faculty of Nursing, Level 3, Edmonton Clinic Health Academy, 11405 87 Avenue, Edmonton, Alberta, Canada T6G 1C9 Email:


In this article, we report the findings of our study on the nature of fatigue in patients diagnosed with chronic fatigue syndrome. Using ethnoscience as a design, we conducted a series of unstructured interviews and card sorts to learn more about how people with chronic fatigue syndrome describe fatigue.

Participants (N = 14) described three distinct domains: tiredness, fatigue, and exhaustion. Most participants experienced tiredness prior to diagnosis, fatigue during daily life, and exhaustion after overexertion.

We also discuss participants’ ability to adapt to a variety of stressors and prevent shifts to exhaustion, and relate our findings to stress theory and other current research. Primary strategies that promoted adaptation to stressors included pacing and extended rest periods.

These findings can aid health care professionals in detecting impending shifts between tiredness, fatigue, and exhaustion and in improving adaptive strategies, thereby improving quality of life.

From Neural Regeneration Research, 18 March 2015.

Fatigue sensation following peripheral viral infection is triggered by neuroinflammation: who will answer these questions?

Masanori Yamato, Yosky Kataoka
Cellular Function Imaging Team, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan
Correspondence Address: Yosky Kataoka, Cellular Function Imaging Team, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 Japan


Fatigue is best defined as difficulty in initiating or sustaining voluntary activities, and is thought to be accompanied by deterioration of performance. Fatigue can be caused by many factors such as physical and mental stress, disturbance in the circadian rhythm, and various diseases. For example, following the flu or other types of infections, everyone has experienced a sense of fatigue that can last for days or weeks.

The fatigue sensation is thought to be one of the signals for the body to suppress physical activity in order to regain health. The mechanism of induction of the fatigue sensation following viral infection has not been well understood.

Although fatigue was once thought to be caused by fever, our recent study with an animal model of viral infection demonstrated that the fatigue sensation is caused not by fever, but rather, by neuroinflammation of brain tissue (Yamato et al., 2014).

A positron emission tomography (PET) study in patients with chronic fatigue syndrome/myalgic encephalomyelitis revealed that activation of microglia is involved in neuroinflammation in the brain, and indicated that the intensity of the PET signals evaluating the presence of neuroinflammation was associated with the severity of neuropsychological symptoms (Nakatomi et al., 2014).

Other studies have indicated that neuroinflammation is an important precipitating event in chronic neurological disorders including Alzheimer's disease, Parkinson's disease, and depression (Song and Wang, 2011; Fan et al., 2014). Therefore, an understanding of the regulatory mechanisms of neuroinflammation and the prevention of entering the chronic state is important.

Acta Paediatr. 2015 Jan 31. doi: 10.1111/apa.12950. [Epub ahead of print]

Study findings challenge the content validity of the Canadian Consensus Criteria for adolescent chronic fatigue syndrome.

Asprusten TT, Fagermoen E, Sulheim D, Skovlund E, Sørensen Ø, Mollnes TE, Wyller VB.
Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Oslo, Norway.



The 2003 Canadian Consensus Criteria for chronic fatigue syndrome (CFS) are often assumed to suggest low-grade systemic inflammation, but have never been formally validated. This study explored the content validity of the Criteria in a sample of adolescents with CFS selected according to a wide case definition.


A total of 120 patients with CFS with a mean age of 15.4 years (range 12-18 years) included in the NorCAPITAL project were post hoc subgrouped according to the Canadian Consensus Criteria. Those who satisfied the criteria (Criteria positive) and those who did not (Criteria negative) were compared across a wide range of disease markers and markers of prognosis.


A total of 46 patients were classified as Criteria positive, 69 were classified as Criteria negative, and five could not be classified. All disease markers were equal across the two groups, except the digit span backward test of cognitive function, which showed poorer performance in the Criteria-positive group. Also, the prognosis over a 30-week period was equal between the groups.


This study questions the content validity of the Canadian Consensus Criteria, as few differences were found between adolescent patients with CFS who did and did not satisfy the Criteria.

From International Journal of Immunopathology and Pharmacology, 28 March 2015.

Chronic fatigue syndrome: Features of a population of patients from northern Italy.

Capelli E(1), Lorusso L(2), Ghitti M(1), Venturini L(3), Cusa C(4), Ricevuti G(5,*)
1) Immunology and Genetic Analysis Laboratory, Department of Earth and
Environmental Sciences, University of Pavia, Pavia, Italy.
2) Department of Neurology, Mellino Mellini Hospital, Chiari, Brescia,
3) Department of Internal Medicine and Therapeutics, University of
Pavia, Pavia, Italy Cellular Pathophysiology and Clinical Immunology
Laboratory, University of Pavia, Pavia, Italy.
4) Department of Internal Medicine and Therapeutics, University of
Pavia, Pavia, Italy.
5) Department of Internal Medicine and Therapeutics, University of
Pavia, Pavia, Italy Cellular Pathophysiology and Clinical Immunology
Laboratory, University of Pavia, Pavia, Italy


In this study we analyzed the clinical features of a population of Italian patients with chronic fatigue syndrome (CFS) diagnosed according to the CDC-1994 criteria. The aim was to investigate CFS patients and their relatives, in order to search for events related to the onset of the disease and to identify correlations with other diseases.

The analysis was carried out by examining medical records belonging to 82 patients suffering from the syndrome. The
documentation was collected between 2008 and 2011 and provided by the non-profit Italian organization AMCFS (Associazione Malati di CFS).

The influence of gender on the age of onset and association with potential risk factors were investigated in patients and in their relatives. From the results a significant correlation between the age of onset and autoimmunity was observed.

From BMC Medicine, 1 April 2015.

The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders

Gerwyn Morris(1,*) and Michael Berk(2,3,4,5)
1) Tir Na Nog, Bryn Road seaside 87, Llanelli, Cardiff SA152LW, Wales, UK
2) IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong 3220, Australia
3) Orygen Youth Health Research Centre and the Centre of Youth Mental Health, Poplar Road 35, Parkville 3052, Australia
4) The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, Royal Parade 30, Parkville 3052, Australia
5) Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, Parkville 3052, Australia



Mitochondrial dysfunction and defects in oxidative metabolism are a characteristic feature of many chronic illnesses not currently classified as mitochondrial diseases. Examples of such illnesses include bipolar disorder, multiple sclerosis, Parkinson’s disease, schizophrenia, depression, autism, and chronic fatigue syndrome.


While the majority of patients with multiple sclerosis appear to have widespread mitochondrial dysfunction and impaired ATP production, the findings in patients diagnosed with Parkinson’s disease, autism, depression, bipolar disorder schizophrenia and chronic fatigue syndrome are less consistent, likely reflecting the fact that these diagnoses do not represent a disease with a unitary pathogenesis and pathophysiology. However, investigations have revealed the presence of chronic oxidative stress to be an almost invariant finding in study cohorts of patients afforded each diagnosis. This state is characterized by elevated reactive oxygen and nitrogen species and/or reduced levels of glutathione, and goes hand in hand with chronic systemic inflammation with elevated levels of pro-inflammatory cytokines.


This paper details mechanisms by which elevated levels of reactive oxygen and nitrogen species together with elevated pro-inflammatory cytokines could conspire to pave a major road to the development of mitochondrial dysfunction and impaired oxidative metabolism seen in many patients diagnosed with these disorders.

From The FASEB Journal, published by the Federation of American Societies for Experimental Biology, April 2015.

The Role of Cytokines in Muscle Fatigue in Patients with Chronic Fatigue Syndrome (CFS).

Kate Earl(1), Giorgos Sakellariou(1), Daniel Owens(2), Melanie Sinclair(1), Manuel Fenech(1), Graeme Close(2), Clare Lawton(3), Louise Dye(3), Micheal Beadsworth(1) and Anne McArdle(1)
1) Institute of Ageing and Chronic Disease University of Liverpool United Kingdom
2) RISES Liverpool John Moores University United Kingdom
3) Psychological Sciences University of Leeds United Kingdom


CFS is characterized by profound levels of persistent/recurrent fatigue. It is proposed that chronic, low level inflammation may play a role in this fatigue.

We recruited 100 untreated patients with CFS (average age 33±12) and 100 age and sex matched healthy controls (HCs).

Serum levels of TNF-α were assessed using ELISA. Subjective fatigue was determined by questionnaire and muscle function tests were undertaken in subgroups in which maximal voluntary contraction (MVC), electrically stimulated muscle force generation and rate of fatigue were assessed in the quadriceps muscle.

Subjective fatigue was higher in patients with CFS compared with HCs. Preliminary analyses showed that serum TNF-α was undetectable in 97% of HCs, whereas 15% of patients with CFS had detectable (4.4+/-0.18pg/ml) serum TNF-α. MVC was significantly reduced in subjects with CFS compared with HCs.

No difference was seen in stimulated muscle fatigue between groups.

This preliminary data suggests that a sub-group of patients with CFS may have low level inflammation and analyses are underway to further characterise other inflammatory markers in serum and muscle of these patients and to determine whether such changes could affect indices of muscle function or central fatigue.

Funded by MRC, BBSRC and the ME Association.

Shopping Basket