From Biological Psychiatry, published online 31 August 2016.
Prefrontal Structure Varies as a Function of Pain Symptoms in Chronic Fatigue Syndrome.
van der Schaaf ME(1), De Lange FP(2), Schmits IC(3), Geurts DE(4), Roelofs K(3), van der Meer JW(5), Toni I(3), Knoop H(6).
1) Expert Centre for Chronic Fatigue, Nijmegen; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroimaging, Radboud University Nijmegen, Nijmegen. Electronic address: email@example.com.
2) Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroimaging, Radboud University Nijmegen, Nijmegen.
3) Expert Centre for Chronic Fatigue, Nijmegen.
4) Department of Psychiatry, Radboud University Medical Center, Nijmegen; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroimaging, Radboud University Nijmegen, Nijmegen; Adult Personality Disorder Service, South London and Maudsley National Health Service Foundation Trust, London, United Kingdom.
5) Department of Internal Medicine, Nijmegen.
6) Expert Centre for Chronic Fatigue, Nijmegen; Department of Medical Psychology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Chronic fatigue syndrome (CFS) is characterized by severe fatigue persisting for ≥6 months and leading to considerable impairment in daily functioning. Neuroimaging studies of patients with CFS have revealed alterations in prefrontal brain morphology. However, it remains to be determined whether these alterations are specific for fatigue or whether they relate to other common CFS symptoms (e.g., chronic pain, lower psychomotor speed, and reduced physical activity).
We used magnetic resonance imaging to quantify gray matter volume (GMV) and the N-acetylaspartate and N-acetylaspartylglutamate/creatine ratio (NAA/Cr) in a group of 89 women with CFS. Building on previous reports, we tested whether GMV and NAA/Cr in the dorsolateral prefrontal cortex are associated with fatigue severity, pain, psychomotor speed, and physical activity, while controlling for depressive symptoms. We also considered GMV and NAA/Cr differences between patients with CFS and 26 sex-, age-, and education-matched healthy controls.
The presence of pain symptoms was the main predictor of both GMV and NAA/Cr in the left dorsolateral prefrontal cortex of patients with CFS. More pain was associated with reduced GMVs and NAA/Cr, over and above the effects of fatigue, depressive symptoms, physical activity, and psychomotor speed. In contrast to previous reports and despite a large representative sample, global GMV did not differ between the CFS and healthy control groups.
CFS, as diagnosed by Centers for Disease Control and Prevention criteria, is not a clinical entity reliably associated with reduced GMV. Individual variation in the presence of pain, rather than fatigue, is associated with neuronal alterations in the dorsolateral prefrontal cortex of patients with CFS.
FromBehavioural and Cognitive Psychotherapy, 18 January 2017.
Chronic Fatigue Syndrome: Cognitive, behavioural and emotional processing vulnerability factors
Samantha K. Brooks(1), Trudie Chalder(1), Katharine A. Rimes(2)
1) Department of Psychological Medicine,King’s College London, Institute of Psychiatry,Weston Education Centre,Cutcombe Road, London SE5 9RJ.
2) King’s College London, Institute of Psychiatry,Psychology and Neuroscience,Department of Psychology,Henry Wellcome Building, De Crespigny Park,London SE5 8AF.
Cognitive-behaviour al models of chronic fatigue syndrome (CFS) suggest that personality factors such as perfectionism and high moral standards may contribute to the development of CFS.
To investigate cognitive, behavioural and emotional processing risk factors for CFS.
CFS patients (n = 67) at a UK specialist clinic completed questionnaires about psychological characteristics both currently and retrospectively (6 months pre-CFS onset). Responses were compared with those of healthy individuals (n=73) who rated their current characteristics. Forty-four relatives retrospectively rated the pre-morbid psychological characteristics of the CFS participants.
CFS patients showed similar levels of current perfectionism to controls, though higher pre-morbid perfectionism. CFS patients showed greater self-sacrificial beliefs and more unhelpful beliefs about experiencing and expressing negative emotions, both currently but more markedly prior to onset. In the 6 months pre-illness onset, CFS patients showed more disruption to their primary goal and greater general stress than controls. Ratings of pre-morbid psychological characteristics by relatives were consistent with patients’ self-reports. The extent of overinvestment in one goal was significantly associated with fatigue.
Perfectionism, self-sacrificial tendencies, unhelpful beliefs about emotions, and perceived stress may be present to a greater extent pre-morbidly in CFS patients compared with healthy individuals.
From Psychological Medicine, 23 January 2017 [Epub ahead of print].
Heterogeneity in chronic fatigue syndrome – empirically defined subgroups from the PACE trial.
Williams TE(1), Chalder T(2), Sharpe M(3), White PD(1).
1) Centre for Psychiatry, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Queen Mary University of London, London,UK.
2) Academic Department of Psychological Medicine,King’s College London, Weston Education Centre,London,UK.
3) Department of Psychiatry,Psychological Medicine Research, University of Oxford,Oxford,UK.
Chronic fatigue syndrome is likely to be a heterogeneous condition. Previous studies have empirically defined subgroups using combinations of clinical and biological variables. We aimed to explore the heterogeneity of chronic fatigue syndrome.
We used baseline data from the PACE trial, which included 640 participants with chronic fatigue syndrome. Variable reduction, using a combination of clinical knowledge and principal component analyses, produced a final dataset of 26 variables for 541 patients. Latent class analysis was then used to empirically define subgroups.
The most statistically significant and clinically recognizable model comprised five subgroups. The largest, ‘core’ subgroup (33% of participants), had relatively low scores across all domains and good self-efficacy. A further three subgroups were defined by: the presence of mood disorders (21%); the presence of features of other functional somatic syndromes (such as fibromyalgia or irritable bowel syndrome) (21%); or by many symptoms – a group which combined features of both of the above (14%). The smallest ‘avoidant-inactive’ subgroup was characterized by physical inactivity, belief that symptoms were entirely physical in nature, and fear that they indicated harm (11%). Differences in the severity of fatigue and disability provided some discriminative validation of the subgroups.
In addition to providing further evidence for the heterogeneity of chronic fatigue syndrome, the subgroups identified may aid future research into the important aetiological factors of specific subtypes of chronic fatigue syndrome and the development of more personalized treatment approaches.
From BMC Immunology (open access), 28 January 2017.
Giardia-specific cellular immune responses in post-giardiasis chronic fatigue syndrome
Kurt Hanevik(1,2), Einar Kristoffersen(1,3), Kristine Mørch(1,2), Kristin Paulsen Rye(1), Steinar Sørnes(1), Staffan Svärd(4), Øystein Bruserud(1) and Nina Langeland(1,2).
1) Department of Clinical Science, Lab-building 8.floor, University of Bergen
2) Center for Tropical Infectious Diseases, Haukeland University Hospital
3) Department of immunology and transfusion medicine, Haukeland University Hospital
The role of pathogen specific cellular immune responses against the eliciting pathogen in development of post-infectious chronic fatigue syndrome (PI-CFS) is not known and such studies are difficult to perform. The aim of this study was to evaluate specific anti-Giardia cellular immunity in cases that developed CFS after Giardia infection compared to cases that recovered well. Patients reporting chronic fatigue in a questionnaire study three years after a Giardia outbreak were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for CFS and idiopathic chronic fatigue. Giardia specific immune responses were evaluated in 39 of these patients by proliferation assay, T cell activation and cytokine release analysis. 20 Giardia exposed non-fatigued individuals and 10 healthy unexposed individuals were recruited as controls.
Patients were clinically classified into CFS (n = 15), idiopathic chronic fatigue (n = 5), fatigue from other causes (n = 9) and recovered from fatigue (n = 10). There were statistically significant antigen specific differences between these Giardia exposed groups and unexposed controls. However, we did not find differences between the Giardia exposed fatigue classification groups with regard to CD4 T cell activation, proliferation or cytokine levels in 6 days cultured PBMCs. Interestingly, sCD40L was increased in patients with PI-CFS and other persons with fatigue after Giardia infection compared to the non-fatigued group, and correlated well with fatigue levels at the time of sampling.
Our data show antigen specific cellular immune responses in the groups previously exposed to Giardia and increased sCD40L in fatigued patients.