TGI Friday! | Our weekly round-up of recently published research abstracts | 22 July 2016

July 22, 2016

From Biochemical and Biophysical Research Communications, published online 7 July 2016.

Human herpesvirus 6 and 7 are biomarkers for fatigue, which distinguish between physiological fatigue and pathological fatigue

Ryo Aoki(a), Nobuyuki Kobayashi(b), Go Suzuki©, Hirohiko Kuratsune(d,e), Kazuya Shimada(b), Naomi Oka(b), Mayumi Takahashi(b), Wataru Yamadera(a), Masayuki Iwashita(a), Shinichi Tokuno(f), Masashi Nibuya(g), Masaaki Tanichi(g), Yasuo Mukai(h), Keiji Mitani(i), Kazuhiro Kondo(b), Hiroshi Ito(a), Kazuhiko Nakayama(a)
a) Department of Psychiatry, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan
b) Department of Virology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan
c) Flight Crew Operations and Technology Unit, Japan Aerospace Exploration Agency Houston Office, 18050 Saturn Lane, Suite 310, Houston, TX 77058, USA
d) Clinical Center for Fatigue Science, Osaka City University Graduate School of Medicine, Osaka, Japan
e) Department of Health Science, Faculty of Health Science for Welfare, Kansai University of Welfare Sciences, Osaka, Japan
f) Department of Defense Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan
g) Department of Psychiatry, National Defense Medical College, Tokorozawa, Saitama, Japan
h) Military Medicine Research Unit, Test and Evaluation Command, Japan Ground Self Defense Force, Setagaya, Tokyo, Japan
i) Department of Internal Medicine, Japan Self-Defense Force Central Hospital, Setagaya, Tokyo, Japan


• Salivary HHV-6 and HHV-7 can be used for assessment of physiological fatigue.
• Activation and differentiation of macrophages are needed for viral reactivation.
• Salivary HHV-6 and HHV-7 do not increase with pathological fatigue.
• Salivary HHV-6/7 can distinguish between physiological and pathological fatigue.


Fatigue reduces productivity and is a risk factor for lifestyle diseases and mental disorders. Everyone experiences physiological fatigue and recovers with rest. Pathological fatigue, however, greatly reduces quality of life and requires therapeutic interventions. It is therefore necessary to distinguish between the two but there has been no biomarker for this.

We report on the measurement of salivary human herpesvirus (HHV-) 6 and HHV-7 as biomarkers for quantifying physiological fatigue. They increased with military training and work and rapidly decreased with rest. Our results suggested that macrophage activation and differentiation were necessary for virus reactivation.

However, HHV-6 and HHV-7 did not increase in obstructive sleep apnea syndrome (OSAS), chronic fatigue syndrome (CFS) and major depressive disorder (MDD), which are thought to cause pathological fatigue. Thus, HHV-6 and HHV-7 would be useful biomarkers for distinguishing between physiological and pathological fatigue.

Our findings suggest a fundamentally new approach to evaluating fatigue and preventing fatigue-related diseases.

From DePaul University, Chicago – DePaul Discoveries, Volume 5, Issue 1.

The Role of Infectious and Stress-related Onsets in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Symptomatology and Functioning

Andrew R. Devendorf, Abigail A. Brown, Leonard A. Jason
Department of Psychology, DePaul University, Chicago, USA


This study examined how the mode of onset for myalgic encephalomyelitis and chronic fatigue syndrome (ME and CFS) impacts patients’ presenting symptomatology. Specifically, this study investigated the differences between the most commonly reported ME and CFS onsets: infectious, stress-related, and a combined infectious and stress-related onset (referred to as ‘combined onset’).

Three patient samples were combined and utilized. All participants met Fukuda et al. (1994) criteria and self-reported their illness onset. Analyses showed the infectious group reported the most impairment for general health functioning — which relates to the susceptibility of getting or feeling sick — in comparison to the stress-related group.

Meanwhile, both the stress-related and combined groups reported more impairment for mental health functioning than the infectious group.

Lastly, the infectious and combined groups reported worse autonomic and immune symptomatology than the stress group. These findings illustrate that the mode of onset for ME and CFS could play a factor in a patient’s prognosis. An infectious onset might lead to worse physical and somatic symptoms, while a stress onset might lead to worse psychological functioning.

These findings are consistent with prior research. Future research should continue investigating the differences among patients based on illness onset, as well as other factors (e.g., psychiatric co-morbidity).

From PLoS One, 14 July 2016.

Aberrant Resting-State Functional Connectivity in the Salience Network of Adolescent Chronic Fatigue Syndrome

Laura Anne Wortinger, Tor Endestad, Annika Maria D. Melinder, Merete Glenne Øie, Andre Sevenius, Vegard Bruun Wyller


Neural network investigations are currently absent in adolescent chronic fatigue syndrome (CFS). In this study, we examine whether the core intrinsic connectivity networks (ICNs) are altered in adolescent CFS patients.

Eighteen adolescent patients with CFS and 18 aged matched healthy adolescent control subjects underwent resting-state functional magnetic resonance imaging (rfMRI). Data was analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks.

Intrinsic connectivity was evaluated in the default mode network (DMN), salience network (SN), and central executive network (CEN). Associations between network characteristics and symptoms of CFS were also explored.

Adolescent CFS patients displayed a significant decrease in SN functional connectivity to the right posterior insula compared to healthy comparison participants, which was related to fatigue symptoms.

Additionally, there was an association between pain intensity and SN functional connectivity to the left middle insula and caudate that differed between adolescent patients and healthy comparison participants.

Our findings of insula dysfunction and its association with fatigue severity and pain intensity in adolescent CFS demonstrate an aberration of the salience network which might play a role in CFS pathophysiology.

From Manual Therapy, September 2016.

Kinesiophobia and maladaptive coping strategies prevent improvements in pain catastrophizing following pain neuroscience education in fibromyalgia/chronic fatigue syndrome: Pooled results from 2 randomized controlled trials

A. Malfliet, J. Van Oosterwijck, M. Meeus, B. Cagnie, L. Danneels, M. Dolphens, R. Buyl, J. Nijs


Many patients with chronic fatigue syndrome (CFS) and/or fibromyalgia (FM) have no understanding of their condition, leading to maladaptive pain cognitions and coping strategies.

These should be tackled during therapy, e.g. by providing pain neurophysiology education (PNE). Although the positive effects of PNE are well-established in chronic pain populations, it remains unclear why some patients benefit more than others.

Identifying predictive factors for therapy would add great value to clinical practice.

From PLoS One (open access), 18 July 2016.

Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome

Peter C. Rowe(1), Kevin R. Fontaine(2), Megan Lauver(1), Samantha E. Jasion(1), Colleen L. Marden(1), Malini Moni(1), Carol B. Thompson(3), Richard L. Violand(4).
1) Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
2) Department of Health Behavior, University of Alabama at Birmingham School of Public Health, Birmingham, Alabama, United States of America
3) Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
4) Rick Violand, PT LLC, Ellicott City, Maryland, United States of America


Chronic fatigue syndrome (CFS) is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress.

In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals. In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls.

We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15-minute period of passive supine straight leg raise (true neuromuscular strain) or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline.

Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0–10 scale, and summed to create a composite symptom score.

Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04) and concentration difficulties (P = 0.02) as well as increased composite symptom scores (all P = 0.03) during the maneuver.

After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001) and for the composite symptom score (P = 0.005).

During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls.

We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours.

These findings support our preliminary observations that increased mechanical sensitivity may be a contributor to the provocation of symptoms in this disorder.

From BMC Family Practice (open access), 19 July 2016.

Investigating unexplained fatigue in general practice with a particular focus on CFS/ME

Amolak S Bansal
Department of Immunology and Allergy, St. Helier Hospital
The Sutton CFS Service, Sutton Hospital


Unexplained fatigue is not infrequent in the community. It presents a number of challenges to the primary care physician and particularly if the clinical examination and routine investigations are normal. However, while fatigue is a feature of many common illnesses, it is the main problem in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This is a poorly understood condition that is accompanied by several additional symptoms which suggest a subtle multisystem dysfunction. Not infrequently it is complicated by sleep disturbance and alterations in attention, memory and mood.

Specialised services for the diagnosis and management of CFS/ME are markedly deficient in the UK and indeed in virtually all countries around the world. However, unexplained fatigue and CFS/ME may be confidently diagnosed on the basis of specific clinical criteria combined with the normality of routine blood tests. The latter include those that assess inflammation, autoimmunity, endocrine dysfunction and gluten sensitivity. Early diagnosis and intervention in general practice will do much to reduce patient anxiety, encourage improvement and prevent expensive unnecessary investigations.

There is presently an on-going debate as to the precise criteria that best confirms CFS/ME to the exclusion of other medical and psychiatric/psychological causes of chronic fatigue. There is also some disagreement as to best means of investigating and managing this very challenging condition. Uncertainty here can contribute to patient stress which in some individuals can perpetuate and aggravate symptoms. A simple clinical scoring system and a short list of routine investigations should help discriminate CFS/ME from other causes of continued fatigue.

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