TGI Friday! Our weekly round-up of recently published research abstracts and other items | 4 October 2013

October 4, 2013

From Journal of Neuropsychology, 24 September 2013 (Epub before print).

Attention network test: Assessment of cognitive function in chronic fatigue syndrome

Fumiharu Togo(1,*), Gudrun Lange(2,3), Benjamin H. Natelson(4), Karen S. Quigley(3,5)
1) Educational Physiology Laboratory, Graduate School of Education, University of Tokyo, Japan
2) Department of Physical Medicine and Rehabilitation, UMD-New Jersey Medical School, Newark, New Jersey, USA
3) Department of Veteran Affairs, New Jersey Health Care System, East Orange, New Jersey, USA
4) Pain and Fatigue Study Center, Beth Israel Medical Center and Albert Einstein Medical Center, New York City, New York, USA
5) Interdisciplinary Affective Science Laboratory, Northeastern University, Boston, Massachusetts, USA
* Corresponding author (email:


Information processing difficulties are common in patients with chronic fatigue syndrome (CFS).

It has been shown that the time it takes to process a complex cognitive task, rather than error rate, may be the critical variable underlying CFS patients' cognitive complaints.

The Attention Network Task (ANT) developed by Fan and colleagues may be of clinical utility to assess cognitive function in CFS, because it allows for simultaneous assessment of mental response speed, also called information processing speed, and error rate under three conditions challenging the attention system.

Comparison of data from two groups of CFS patients (those with and without comorbid major depressive disorder; n=19 and 22, respectively) to controls (n=29) consistently showed that error rates did not differ among groups across conditions, but speed of information processing did.

Processing time was prolonged in both CFS groups and most significantly affected in response to the most complex task conditions. For simpler tasks, processing time was only prolonged in CFS participants with depression. The data suggest that the ANT may be a task that could be used clinically to assess information processing deficits in individuals with CFS.

From Evaluation and the Health Professions, 23 September 2013. [Epub ahead of print].

Effects of Time Frame on the Recall Reliability of CFS Symptoms

Evans M, Jason LA.


This study serves as an investigation of the reliability of symptom data as reported by individuals with chronic fatigue syndrome (CFS), across three recall time frames (the past week, the past month, and the past 6 months), and at two assessment points (with 1 week in between each assessment).

Multilevel model analyses were used to determine the optimal recall time frame, in terms of test-retest reliability, for each of the Fukuda et al. (1994) case defining symptoms.

Results suggested that the optimal time frame for reliably reporting CFS symptoms was six months for sore throat, lymph node pain, muscle pain, post-exertional malaise, headaches, memory/concentration difficulties, and unrefreshing sleep.

For joint pain, the optimal time frame was one month.

Researchers who are interested in the assessment of CFS symptoms need to take recall time frame into account, especially when the intended goal is to standardize and improve the methods used to reliably and accurately diagnose this complex illness.

From Comprehensive Psychiatry, October 2013 (Published online on 6 June 2013).

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

Sergi Valero(1,*), Naia Saez-Francas(1), Natalia Calvo(1), Jose Alegre(2), Miquel Casas(1)
1) Department of Psychiatry, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Passeig de la Vall d'Hebron 119-129, 08035 Barcelona, Catalonia, Spain
2) Department of Internal Medicine, Hospital Universitari Vall D'Hebron,
Institut de Recerca (VHIR), Universitat Autonoma de Barcelona, Passeig
de la Vall d'Hebron 119-129, 08035 Barcelona, Catalonia, Spain
* Corresponding Author. Email:



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.

From Molecular Neurobiology, 26 September 2013 (Epub ahead of print).

The Emerging Role of Autoimmunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/cfs)

Gerwyn Morris, Michael Berk, Piotr Galecki, Michael Maes
Mumbles Head, Pembrey, Llanelli, UK.


The World Health Organization classifies myalgic encephalomyelitis/chronic fatigue syndrome (ME/cfs) as a nervous system disease. Together with other diseases under the G93 heading, ME/cfs shares a triad of abnormalities involving elevated oxidative and nitrosative stress (O&NS), activation of immuno-inflammatory pathways, and mitochondrial dysfunctions with depleted levels of adenosine triphosphate (ATP) synthesis.

There is also abundant evidence that many patients with ME/cfs (up to around 60 %) may suffer from autoimmune responses. A wide range of reported abnormalities in ME/cfs are highly pertinent to the generation of autoimmunity.

Here we review the potential sources of autoimmunity which are observed in people with ME/cfs. The increased levels of pro-inflammatory cytokines, e.g., interleukin-1 and tumor necrosis factor-α, and increased levels of nuclear factor-κB predispose to an autoimmune environment. Many cytokine abnormalities conspire to produce a predominance of effector B cells and autoreactive T cells.

The common observation of reduced natural killer cell function in ME/cfs is a source of disrupted homeostasis and prolonged effector T cell survival. B cells may be pathogenic by playing a role in autoimmunity independent of their ability to produce antibodies.

The chronic or recurrent viral infections seen in many patients with ME/cfs can induce autoimmunity by mechanisms involving molecular mimicry and bystander activation. Increased bacterial translocation, as observed in ME/cfs, is known to induce chronic inflammation and autoimmunity.

Low ATP production and mitochondrial dysfunction is a source of autoimmunity by inhibiting apoptosis and stimulating necrotic cell death. Self-epitopes may be damaged by exposure to prolonged O&NS, altering their immunogenic profile and become a target for the host’s immune system.

Nitric oxide may induce many faces of autoimmunity stemming from elevated mitochondrial membrane hyperpolarization and blockade of the methionine cycle with subsequent hypomethylation of DNA.

Here we also outline options for treatment involving rituximab and endotherapia.

From the Journal of Translational Medicine, 2 October 2013 (Link shows full text).

A multidisciplinary approach to study a couple of monozygotic twins discordant for the chronic fatigue syndrome: a focus on potential salivary biomarkers

Federica Ciregia(1), Laura Giusti(1), Ylenia Da Valle(1), Elena Donadio(1), Arianna Consensi(2), Camillo Giacomelli(2), Francesca Sernissi(2), Pietro Scarpellini(2), Fabrizio Maggi(3), Antonio Lucacchini(1,*) and Laura Bazzichi(2)
1) Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy
2) Department of clinical and experimental medicine, Division of Rheumatology, University of Pisa, Via Roma 67, 56126 Pisa, Italy
3) Virology Unit, Pisa University Hospital, Via Roma 67, 56126 Pisa, Italy
* Corresponeding author: email:

Abstract (provisional)


Chronic Fatigue Syndrome (CFS) is a severe, systemic illness characterized by persistent, debilitating and medically unexplained fatigue. The etiology and pathophysiology of CFS remains obscure, and diagnosis is formulated through the patient's history and exclusion of other medical causes. Thereby, the availability of biomarkers for CFS could be useful for clinical research.

In the present study, we used a proteomic approach to evaluate the global changes in the salivary profile in a couple of monozygotic twins who were discordant for CFS. The aim was to evaluate differences of salivary protein expression in the CFS patient in respect to his healthy twin.


Saliva samples were submitted to two-dimensional electrophoresis (2DE). The gels were stained with Sypro, and a comparison between CFS subject and the healthy one was performed by the software Progenesis Same Spot including the Analysis of variance (ANOVA test). The proteins spot found with a >=2-fold spot quantity change and p<0.05 were identified by Nano-liquid chromatography electrospray ionization tandem mass spectrometry. To validate the expression changes found with 2DE of 5 proteins (14-3-3 protein zeta/delta, cyclophilin A, Cystatin-C, Protein S100-A7, and zinc-alpha-2-glycoprotein), we used the western blot analysis. Moreover, proteins differentially expressed were functionally analyzed using the Ingenuity Pathways Analysis software with the aim to determine the predominant canonical pathways and the interaction network involved.RESULTSThe analysis of the protein profiles allowed us to find 13 proteins with a different expression in CFS in respect to control. Nine spots were up-regulated in CFS and 4 down-regulated. These proteins belong to different functional classes, such as inflammatory response, immune system and metabolism. In particular, as shown by the pathway analysis, the network built with our proteins highlights the involvement of inflammatory response in CFS pathogenesis.CONCLUSIONSThis study shows the presence of differentially expressed proteins in the saliva of the couple of monozygotic twins discordant for CFS, probably related to the disease. Consequently, we believe the proteomic approach could be useful both to define a panel of potential diagnostic biomarkers and to shed new light on the comprehension of the pathogenetic pathways of CFS.

From ISRN Neuroscience, Volume 2013 (2013), Article ID 784520, 8 pages. Full text available.

Review Article
A Review of Hypothalamic-Pituitary-Adrenal Axis Function in Chronic Fatigue Syndrome

Cara Tomas(1), Julia Newton(1), and Stuart Watson(1,2)
1) Newcastle University, Newcastle upon Tyne NE1 7RU, UK
2) Wolfson Research Centre, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK


Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been found in a high proportion of chronic fatigue syndrome (CFS) patients and includes enhanced corticosteroid-induced negative feedback, basal hypocortisolism, attenuated diurnal variation, and a reduced responsivity to challenge.

A putative causal role for genetic profile, childhood trauma, and oxidative stress has been considered. In addition, the impact of gender is demonstrated by the increased frequency of HPA axis dysregulation in females.

Despite the temporal relationship, it is not yet established whether the endocrine dysregulation is causal, consequent, or an epiphenomenon of the disorder. Nonetheless, given the interindividual variation in the effectiveness of existing biological and psychological treatments, the need for novel treatment strategies such as those which target the HPA axis is clear.

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