Chronic Fatigue Syndrome Group Research Articles

Small-World Network Analysis of Cortical Connectivity in Chronic Fatigue Syndrome Using Quantitative EEG

The aim of this study was to explore the relationship between complex brain networks in people with Chronic Fatigue Syndrome (CFS) and neurocognitive impairment. Quantitative EEG (qEEG) recordings were taken from 14 people with CFS and 15 healthy controls (HCs) during an eye-closed resting condition. Exact low resolution electromagnetic tomography (eLORETA) was used to estimate cortical sources and perform a functional connectivity analysis. The graph theory approach was used to characterize network representations for each participant and derive the “small-worldness” index, a measure of the overall homeostatic balance between local and long-distance connectedness. Results showed that small-worldness for the delta band was significantly lower for patients with CFS compared to HCs. In addition, delta small-worldness was negatively associated with neurocognitive impairment scores on the DePaul Symptom Questionnaire (DSQ). Finally, delta small-worldness indicated a greater risk of complex brain network inefficiency for the CFS group. These results suggest that CFS pathology may be functionally disruptive to small-world networks. In turn, small-world characteristics might serve as a neurophysiological indicator for confirming a biological basis of cognitive symptoms, treatment outcome, and neurophysiological status of people with CFS.

Exercise \u2013 induced changes in cerebrospinal fluid miRNAs in Gulf War Illness, Chronic Fatigue Syndrome and sedentary control subjects

Gulf War Illness (GWI) and Chronic Fatigue Syndrome (CFS) have similar profiles of pain, fatigue, cognitive dysfunction and exertional exhaustion. Post-exertional malaise suggests exercise alters central nervous system functions. Lumbar punctures were performed in GWI, CFS and control subjects after (i) overnight rest (nonexercise) or (ii) submaximal bicycle exercise. Exercise induced postural tachycardia in one third of GWI subjects (Stress Test Activated Reversible Tachycardia, START). The remainder were Stress Test Originated Phantom Perception (STOPP) subjects. MicroRNAs (miRNA) in cerebrospinal fluid were amplified by quantitative PCR. Levels were equivalent between nonexercise GWI (n = 22), CFS (n = 43) and control (n = 22) groups. After exercise, START (n = 22) had significantly lower miR-22-3p than control (n = 15) and STOPP (n = 42), but higher miR-9-3p than STOPP. All post-exercise groups had significantly reduced miR-328 and miR-608 compared to nonexercise groups; these may be markers of exercise effects on the brain. Six miRNAs were significantly elevated and 12 diminished in post-exercise START, STOPP and control compared to nonexercise groups. CFS had 12 diminished miRNAs after exercise. Despite symptom overlap of CFS, GWI and other illnesses in their differential diagnosis, exercise-induced miRNA patterns in cerebrospinal fluid indicated distinct mechanisms for post-exertional malaise in CFS and START and STOPP phenotypes of GWI.

The variation of the 5-hydroxytryptamine system between chronic unpredictable mild stress rats and chronic fatigue syndrome rats induced by forced treadmill running.

The aim of this study was to observe the variation in the 5-hydroxytryptamine (5-HT) system between a chronic unpredictable mild stress (CUMS) model and a chronic fatigue syndrome (CFS) model. The total distance, the crossing pieces, and rearing times in the open-field test of the CUMS group and the CFS group were all less than those of the control group to different degrees. The concentrations of tryptophan, 5-HT, and 5-HIAA of the CUMS group were obviously lower than those of the control group. In the CFS model, the concentrations of tryptophan, 5-HT, and 5-HIAA were obviously higher than those of the control group. The expressions of tryptophan hydroxylase-2 (TPH-2) and 5-HT1A receptor in protein level and mRNA level were also different among the three groups. The expressions of TPH-2 and 5-HT1A were higher in the CFS group than in the CUMS group. The expressions of TPH-2 and 5-HT1A receptor were lower in the CUMS group than in the control group. We can find that in different situations of mood disorders, the variation of 5-HT system may also be opposite.

Dysregulation of cytokine pathways in chronic fatigue syndrome and multiple sclerosis

ABSTRACT Background: Cytokine studies in chronic fatigue syndrome (CFS) have yielded mixed findings. Purpose: This investigation evaluated whether network analysis of cytokine production differs between patients with CFS and multiple sclerosis (MS) as compared to a reference group of healthy controls. Methods: Three subgroups (N = 109) were included: 15 participants who met diagnostic criteria for CFS, 57 participants meeting criteria for MS, and 37 controls. Peripheral blood was obtained and production of a select cytokine profile was determined from stimulated and unstimulated mononuclear cells. Data were generated through the use of a multi-analyte bead suspension array. Pairwise associations were determined for each group, and these associations were used to create a graphical representation of the data. The graph was clustered using an eigenvector community algorithm and results visualized using edges to model the correlations by color and thickness to show direction and strength. Results: The control and MS groups produced a three-neighborhood relationship regardless of cell condition. While producing a three-neighborhood relationship, the MS group differed significantly from the control group as it displayed stronger relationships among pro-inflammatory cytokines. In contrast, the CFS group displayed a three-neighborhood solution when unstimulated. However, when cells from the CFS group were stimulated, a two-neighborhood model was found that exhibited stronger inter-cytokine correlations. The model found in CFS was significantly different from that found in the control and MS groups. Conclusion: CFS was characterized by a pattern of global immunologic activation using network analysis, fundamentally different from those found for either MS or control groups.

Stress vulnerability in adolescents with chronic fatigue syndrome: experimental study investigating heart rate variability and skin conductance responses.

Stress vulnerability has been implicated in adolescent chronic fatigue syndrome (CFS), but has rarely been investigated directly. This study compared psychological and physiological responses to a laboratory social performance task in adolescents with CFS with chronic illness (asthma) and healthy control groups. Adolescents with CFS (n=60), adolescents with asthma (n=31) and healthy adolescents (n=78) completed questionnaires before and after a social performance task. Skin conductance responses (SCR; mean SCR and Max-Min) and heart rate variability (low frequency/high frequency; LF/HF and root mean square difference of successive RR intervals; RMSSD) was measured before, during and after the task. Baseline heart rate variability (HRV) (RMSSD) was significantly lower in the CFS and Asthma groups than the HC. During the speech, the CFS and Asthma groups had higher HRV (LF/HF) than the HC, adjusting for baseline LF/HF. Although the asthma group showed a subsequent reduction in HRV during recovery, the CFS group did not. Similarly, during recovery after the task, the CFS group showed a continued increase in skin conductance (Min-Max), unlike the Asthma and HC groups. Compared to control groups, adolescents with CFS expected to find the task more difficult, were more anxious beforehand and afterwards, rated it as more difficult, evaluated their performance more negatively and had lower observer ratings of performance. Parents of adolescents with CFS expected that their child would perform less well in the task than parents of control participants. Adolescents with CFS showed autonomic nervous system responses that are consistent with chronic stress vulnerability, difficulty coping with acute stress and slower recovery after acute stress. Self-report measures also indicated greater trait, pre- and posttask anxiety in the CFS group.

Gross and fine motor function in fibromyalgia and chronic fatigue syndrome.

PurposeThis paper aimed to investigate motor proficiency in fine and gross motor function, with a focus on reaction time (RT) and movement skill, in patients with fibromyalgia (FM) and chronic fatigue syndrome (CFS) compared to healthy controls (HC).MethodsA total of 60 individuals (20 CFS, 20 FM, and 20 HC), age 19–49 years, participated in this study. Gross motor function in the lower extremity was assessed using a RT task during gait initiation in response to an auditory trigger. Fine motor function in the upper extremity was measured during a precision task (the Purdue Pegboard test) where the number of pins inserted within 30 s was counted.ResultsNo significant differences were found between FM and CFS in any parameters. FM and CFS groups had significantly longer RT than HC in the gait initiation (p=0.001, and p=0.004 respectively). In the Purdue Pegboard test, 20% in the FM group, 15% in the CFS groups, and 0% of HC group, scored below the threshold of the accepted performance. However, there were no significant differences between FM, CFS, and HC in this task (p=0.12).ConclusionCompared to controls, both CFS and FM groups displayed significantly longer RT in the gait initiation task. Generally, FM patients showed the worst results in both tests, although no group differences were found in fine motor control, according to the Purdue Pegboard test.

Neuroendocrine disorder in chronic fatigue syndrome

Background/aim: Neuroendocrine disorders are considered a possible pathogenetic mechanism in chronic fatigue syndrome (CFS). The aim of our study was to determine the function of the hypothalamic-pituitary-adrenal axis (HPA) and thyroid function in women of reproductive age suffering from CFS. Materials and methods: The study included 40 women suffering from CFS and 40 healthy women (15-45 years old). Serum levels of cortisol (0800 and 1800 hours), ACTH, total T4, total T3, and TSH were measured in all subjects. The Fibro Fatigue Scale was used for determination of fatigue level. Results: Cortisol serum levels were normal in both groups. The distinctively positive moderate correlation of morning and afternoon cortisol levels that was observed in healthy women was absent in the CFS group. This may indicate a disturbed physiological rhythm of cortisol secretion. Although basal serum T4, T3, and TSH levels were normal in all subjects, concentrations of T3 were significantly lower in the CFS group. Conclusion: One-time hormone measurement is not sufficient to detect hormonal imbalance in women suffering from CFS. Absence of a correlation between afternoon and morning cortisol level could be a more representative factor for detecting HPA axis disturbance.

Fatigue in an adult attention deficit hyperactivity disorder population: A trans-diagnostic approach.

Trans-diagnostic approaches suggest that key cognitive and behavioural processes maintain symptoms across a wide range of mental health disorders. Fatigue is a common clinical feature of attention deficit hyperactivity disorder (ADHD) in adulthood; however, empirical data supporting its prevalence are lacking. This study aimed to collate outcomes from outpatient services to (1) investigate the prevalence of fatigue in adults with ADHD, (2) examine symptoms of ADHD in adults with chronic fatigue syndrome (CFS), and (3) consider secondary clinical characteristics common to both disorder groups. Measures of self-reported fatigue were compared across groups of adults with ADHD (N=243), CFS (N=86), and healthy controls (HC) (N=211) using a between-subjects cross-sectional design. Groups were also compared on secondary clinical measures of functional impairment, mood, anxiety, sleep, self-efficacy, and their beliefs about the acceptability of expressing emotions. The ADHD group were significantly more fatigued than HC with 62% meeting criteria for fatigue caseness. ADHD symptoms were significantly greater in the CFS group than in HC. ADHD and CFS groups did not differ significantly on measures of functional impairment, mood, and self-efficacy. No significant differences were detected on measures of anxiety when items relating to physical restlessness were removed from the analysis. Adults with ADHD experience greater fatigue than HC. Adults with CFS and ADHD share many trans-diagnostic clinical characteristics, including difficulties with low mood, anxiety, and reduced self-efficacy, which impact upon their overall functioning. Further research is required to investigate extraneous factors mediating fatigue severity in these clinical groups. Fatigue is a common clinical feature of attention deficit hyperactivity disorder (ADHD) in adulthood. Evidence-based interventions for chronic fatigue syndrome could be adapted to address fatigue in ADHD in adults.

Fatigue and psychosocial variables in autoimmune rheumatic disease and chronic fatigue syndrome: A cross-sectional comparison

ObjectiveFatigue is common in autoimmune rheumatic diseases (ARD). This study compared symptom-related cognitions, beliefs, behaviours, quality of sleep, lack of acceptance and distress in participants with ARD such as rheumatoid arthritis (RA), seronegative spondyloarthropathy (SpA), and connective tissue disease (CTD), and participants with chronic fatigue syndrome (CFS). Methods303 participants with RA, SpA, CTD and CFS completed questionnaire measures of fatigue, social adjustment, cognitive-behavioural responses, lack of acceptance, distress and quality of sleep. The RA, SpA and CTD groups were first compared with each other. They were then combined into one group and compared with the CFS group. ResultsThere were no statistically significant differences between the RA, SpA or CTD groups for any of the measures. The CFS group was more fatigued, reported more distress and sleep disturbance and had worse social adjustment than the ARD group after adjustment for age and illness duration. After adjustment for fatigue, age, and illness duration, the CFS group scored more highly on lack of acceptance and avoidance/resting behaviour while the ARD group showed significantly higher levels of catastrophizing, damage beliefs, and symptom focusing than the CFS group. ConclusionFatigue in rheumatic diseases may be perpetuated by similar underlying transdiagnostic processes. The ARD and CFS groups showed similarities but also key differences in their responses to symptoms. Specific aspects of treatment may need to be tailored towards each group. For example, lack of acceptance and avoidance behaviour may be particularly important in perpetuating fatigue in CFS.

Well-being in Chronic Fatigue Syndrome: Relationship to Symptoms and Psychological Distress.

There is growing recognition in psychology that wellness is more than the absence of disease and distress. Well-being has been defined in numerous ways. Two dominant models include Diener, Eunkook, Suh, Lucas and Smith's (1999) model of subjective well-being (SWB) and Ryff's (1989) model of psychological well-being (PWB). In contrast to the abundance of research investigating negative constructs and psychopathology in chronic fatigue syndrome (CFS), there has been a paucity of positive psychology studies. This study had two aims: to examine PWB and SWB and their relationship to symptoms in CFS and to compare PWB scores in a subgroup of the CFS sample to a matched control group. Chronic fatigue syndrome participants (n = 60) completed self-report scales of PWB, SWB, fatigue, anxiety and depression. PWB scores in a subgroup of the CFS sample (n = 42) were compared with those of a matched nonclinical control group (n = 42). Correlations between scales of symptoms and well-being were complex. Well-being dimensions were largely independent of physical components of fatigue but strongly related to psychological components of fatigue and psychological distress. Multiple regression indicated that five dimensions of well-being uniquely predicted symptomatology. Compared with the control group, the CFS group scored significantly lower on five of Ryff's six PWB dimensions, with particularly marked deficits in personal growth, environmental mastery and self-acceptance. This multidimensional assessment of well-being advances our understanding of CFS and offers new treatment targets. Future research must investigate whether interventions targeting theses well-being deficits can boost the efficacy of symptom-focused treatments. Copyright © 2016 John Wiley & Sons, Ltd. Previous psychological research into CFS has largely focused on the identification of negative constructs and CBT, a treatment that targets evidenced-based negative constructs, has demonstrated efficacy in reducing levels of fatigue and disability. However, the majority of people continue to experience psychiatric symptoms and excessive levels of fatigue post-treatment. Finding ways to enhance the efficacy of existing treatments is a clinical priority. There is evidence to suggest that in clinical populations, standard CBT is effective at reducing negative affect and thinking but fails to enhance low levels of positive affect and thinking, implying treatments may be more effective if they promote positive functioning alongside a reduction of negative functioning. Multidimensional models of well-being suggest that well-being is not a single phenomenon, and different psychological disorders may be characterized by varying well-being deficit profiles. Psychological well-being was found to be diminished in CFS participants compared with controls, with particularly marked deficits in personal growth, environmental mastery and self-acceptance, suggesting that these may be particularly important treatment targets. Well-being dimensions within the CFS group were largely independent of physical symptoms but strongly related to psychological symptoms, suggesting what may be causing low levels of well-being in CFS is largely psychological factors and the general impact of living with a chronic illness rather than symptom levels per se.

Attentional and interpretive bias towards illness-related information in chronic fatigue syndrome: A systematic review.

Chronic fatigue syndrome (CFS) is characterized by severe and debilitating fatigue. Studies based on self-report measures suggest negative illness representations, related symptom interpretations, and heightened symptom focusing are maintaining factors of fatigue. This study reviews studies which have investigated these cognitive biases using experimental methods, to (1) review the evidence for information processing biases in CFS; (2) determine the nature of these biases, that is the stages cognitive biases occur and for what type of stimuli; and (3) provide directions for future methodologies in this area. Studies were included that measured attention and interpretation bias towards negative and illness-related information in people with CFS and in a comparison group of healthy controls. PubMed, Ovid, CINAHL, PsycINFO, Web of Science, and EThOS were searched until December 2014. The evidence for cognitive biases was dependent on the methodology employed as well as the type and duration of the stimuli presented. Modified Stroop studies found weak evidence of an attentional bias in CFS populations, whereas visual-probe studies consistently found an attentional bias in CFS groups for health-threatening information presented for 500ms or longer. Interpretative bias studies which required elaborative processing, as opposed to a spontaneous response, found an illness-related interpretive bias in the CFS group compared to controls. Some people with CFS have biases in the way they attend to and interpret somatic information. Such cognitive processing biases may maintain illness beliefs and symptoms in people with CFS. This review highlights methodological issues in experimental design and makes recommendations to aid future research to forge a consistent approach in cognitive processing research. Statement of contribution What is already known on this subject? Studies based on self-report measures suggest negative illness representations, related symptom interpretations, and heightened symptom focusing contribute to the maintenance of chronic fatigue. Experimental studies in other clinical populations, such as patients with anxiety, depression, and chronic pain, have identified illness-specific biases in how information is implicitly attended to and interpreted, which has a causal role in these conditions. What does this study add? This is the first review of implicit cognitive processes in chronic fatigue syndrome (CFS). Sustained attention and negative interpretations of somatic information may reinforce negative illness beliefs. Cognitive processes have a role to play in the cognitive behavioural model of CFS.

Emotional suppression in chronic fatigue syndrome: Experimental study.

Emotional processing differences in chronic fatigue syndrome (CFS) have been reported but have rarely been investigated experimentally. This study used self-report, observer ratings, and electrodermal responses to test hypotheses about emotion suppression and autonomic reactivity. Eighty adults with CFS and 80 healthy controls (HC) watched a distressing film clip. Half of each group were instructed to suppress their emotions and half were told to express their feelings as they wished. Their reactions were filmed and rated by independent observers. Electrodermal activity (skin conductance response) was used as a measure of sympathetic nervous system arousal. CFS participants reported higher anxiety and sadness than the HC, both before and after the film. However, observers rated the CFS group as having lower emotional expression than HC in both emotional suppression and expression choice conditions. Beliefs about the unacceptability of negative emotions were associated with greater self-reported suppression. Electrodermal responses were greater in the CFS group than HC participants. Higher skin conductance responses were associated with larger posttask increases in fatigue in the CFS participants but not in the HC. CFS participants had lower observer-rated emotional expression than HC, despite greater distress and higher autonomic arousal. This may have implications for their ability to access social support at times of stress. As the degree of autonomic arousal was associated with short-term increases in fatigue in the CFS participants, this requires further investigation as a contributory factor for this condition. (PsycINFO Database Record

Reduced cardiac volumes in chronic fatigue syndrome associate with plasma volume but not length of disease: a cohort study

ObjectivesTo explore potential mechanisms that underpin the cardiac abnormalities seen in chronic fatigue syndrome (CFS) using non-invasive cardiac impedance, red cell mass and plasma volume measurements.MethodsCardiac MR (MR) examinations were...

Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study.

BackgroundChronic fatigue syndrome (CFS) is a common and disabling disorder, and a major threat against adolescent health. The pathophysiology is unknown, but alteration of neuroendocrine control systems might be a central element, resulting in attenuation of the hypothalamus–pituitary–adrenalin (HPA) axis and enhancement of the sympathetic/adrenal medulla (SAM) system. This study explored differences in neuroendocrine control mechanisms between adolescent CFS patients and healthy controls, and whether characteristics of the control mechanisms are associated with important clinical variables within the CFS group.MethodsCFS patients 12–18 years of age were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied. A comparable group of healthy controls were recruited from local schools. A total of nine hormones were assayed and subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and daily physical activity was recorded by an accelerometer.ResultsA total of 120 CFS patients and 68 healthy controls were included. CFS patients had significantly higher levels of plasma norepinephrine, plasma epinephrine and plasma FT4, and significantly lower levels of urine cortisol/creatinine ratio. Subgrouping according to other case definitions as well as adjusting for confounding factors did not alter the results. Multivariate linear regression models as well as network analyses revealed different interrelations between hormones of the HPA axis, the SAM system, and the thyroid system in CFS patients and healthy controls. Also, single hormone degree centrality was associated with clinical markers within the CFS group.ConclusionThis study reveals different interrelation between hormones of the HPA axis, the SAM system, and the thyroid system in CFS patients and healthy controls, and an association between hormone control characteristics and important clinical variables in the CFS group. These results add to the growing insight of CFS disease mechanisms.Trial registration Clinical Trials NCT01040429

Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study.

PurposeTo examine progressive brain changes associated with chronic fatigue syndrome (CFS).Materials and MethodsWe investigated progressive brain changes with longitudinal MRI in 15 CFS and 10 normal controls (NCs) scanned twice 6 years apart on the same 1.5 Tesla (T) scanner. MR images yielded gray matter (GM) volumes, white matter (WM) volumes, and T1‐ and T2‐weighted signal intensities (T1w and T2w). Each participant was characterized with Bell disability scores, and somatic and neurological symptom scores. We tested for differences in longitudinal changes between CFS and NC groups, inter group differences between pooled CFS and pooled NC populations, and correlations between MRI and symptom scores using voxel based morphometry. The analysis methodologies were first optimized using simulated atrophy.ResultsWe found a significant decrease in WM volumes in the left inferior fronto‐occipital fasciculus (IFOF) in CFS while in NCs it was unchanged (family wise error adjusted cluster level P value, P FWE < 0.05). This longitudinal finding was consolidated by the group comparisons which detected significantly decreased regional WM volumes in adjacent regions (P FWE < 0.05) and decreased GM and blood volumes in contralateral regions (P FWE < 0.05). Moreover, the regional GM and WM volumes and T2w in those areas showed significant correlations with CFS symptom scores (P FWE < 0.05).ConclusionThe results suggested that CFS is associated with IFOF WM deficits which continue to deteriorate at an abnormal rate. J. Magn. Reson. Imaging 2016;44:1301–1311.

Methods of applying the 1994 case definition of chronic fatigue syndrome – impact on classification and observed illness characteristics

BackgroundMultiple case definitions are in use to identify chronic fatigue syndrome (CFS). Even when using the same definition, methods used to apply definitional criteria may affect results. The Centers for Disease Control and Prevention (CDC) conducted two population-based studies estimating CFS prevalence using the 1994 case definition; one relied on direct questions for criteria of fatigue, functional impairment and symptoms (1997 Wichita; Method 1), and the other used subscale score thresholds of standardized questionnaires for criteria (2004 Georgia; Method 2). Compared to previous reports the 2004 CFS prevalence estimate was higher, raising questions about whether changes in the method of operationalizing affected this and illness characteristics.MethodsThe follow-up of the Georgia cohort allowed direct comparison of both methods of applying the 1994 case definition. Of 1961 participants (53 % of eligible) who completed the detailed telephone interview, 919 (47 %) were eligible for and 751 (81 %) underwent clinical evaluation including medical/psychiatric evaluations. Data from the 499 individuals with complete data and without exclusionary conditions was available for this analysis.ResultsA total of 86 participants were classified as CFS by one or both methods; 44 cases identified by both methods, 15 only identified by Method 1, and 27 only identified by Method 2 (Kappa 0.63; 95 % confidence interval [CI]: 0.53, 0.73 and concordance 91.59 %). The CFS group identified by both methods were more fatigued, had worse functioning, and more symptoms than those identified by only one method. Moderate to severe depression was noted in only one individual who was classified as CFS by both methods. When comparing the CFS groups identified by only one method, those only identified by Method 2 were either similar to or more severely affected in fatigue, function, and symptoms than those only identified by Method 1.ConclusionsThe two methods demonstrated substantial concordance. While Method 2 classified more participants as CFS, there was no indication that they were less severely ill or more depressed. The classification differences do not fully explain the prevalence increase noted in the 2004 Georgia study. Use of standardized instruments for the major CFS domains provides advantages for disease stratification and comparing CFS patients to other illnesses.

Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in Chronic Fatigue Syndrome.

Autonomic changes are often associated with the chronic fatigue syndrome (CFS), but their pathogenetic role is unclear and brain imaging investigations are lacking. The vasomotor centre and, through it, nuclei in the midbrain and hypothalamus play a key role in autonomic nervous system regulation of steady state blood pressure (BP) and heart rate (HR). In this exploratory cross-sectional study, BP and HR, as indicators of autonomic function, were correlated with volumetric and T1- and T2-weighted spin-echo (T1w and T2w) brain MRI in 25 CFS subjects and 25 normal controls (NC). Steady state BP (systolic, diastolic and pulse pressure) and HR in two postures were extracted from 24 h blood pressure monitoring. We performed (1) MRI versus autonomic score interaction-with-group regressions to detect locations where regression slopes differed in the CFS and NC groups (collectively indicating abnormality in CFS), and (2) MRI regressions in the CFS and NC groups alone to detect additional locations with abnormal correlations in CFS. Significant CFS regressions were repeated controlling for anxiety and depression (A&D). Abnormal regressions were detected in nuclei of the brainstem vasomotor centre, midbrain reticular formation and hypothalamus, but also in limbic nuclei involved in stress responses and in prefrontal white matter. Group comparisons of CFS and NC did not find MRI differences in these locations. We propose therefore that these regulatory nuclei are functioning correctly, but that two-way communication between them is impaired in CFS and this affects signalling to/from peripheral effectors/sensors, culminating in inverted or magnified correlations. This single explanation for the diverse abnormal correlations detected here consolidates the conclusion for a brainstem/midbrain nerve conduction deficit inferred earlier (Barnden et al., 2015). Strong correlations were also detected in isolated NC regressions.

Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study

Chronic fatigue (CF) is a common reason for consulting a physician due to affecting quality of life, but only a few effective treatments are available. The aim of this study was to examine the effectiveness of subcutaneous injection of the human placental extract (HPE) on medically indescribable cases of CF and safety in a randomized, double-blind, placebo-controlled clinical trial. A total of 78 subjects with CF were randomly assigned to either a HPE group or a placebo group. Subjects in the HPE group were treated with HPE three times a week subcutaneously for 6 weeks, whereas those in the placebo group with normal saline. Then, the fatigue severity scale (FSS), visual analog scale (VAS) and multidimensional fatigue inventory (MFI) were measured in both CF group and chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) subgroup. The FSS, VAS and MFI score at baseline were not different between the HPE and placebo group in total subjects with CF. In CFS group, the FSS (p=0.0242), VAS (p=0.0009) and MFI (p=0.0159) scores measured at the end of the study period decreased more in the HPE group than in the placebo group when compared with those at the baseline. There were no significant differences between the HPE group and placebo group in the mean change from baseline in FSS, VAS, and MFI in subjects with ICF during the study period. The subcutaneous injection of HPE was effective in the improvement of CFS.

Autonomic function in chronic fatigue syndrome with and without painful temporomandibular disorder

Background: Chronic fatigue syndrome (CFS) is heterogeneous in nature, yet no clear subclassifications currently exist. There is evidence of dysautonomia in almost 90% of patients and CFS is often co-morbid with conditions associated with autonomic nervous system (ANS) dysfunction, such as temporomandibular disorders (TMD). The present study examined the point prevalence of TMD in a sample of people with CFS and explored whether co-morbidity between the conditions is associated with greater ANS dysfunction than CFS alone. Method: Fifty-one patients and 10 controls underwent screening for TMD. They completed a self-report measure of ANS function (COMPASS-31) and objective assessment of heart rate variability during rest and standing (derived using spectral analysis). Frequency densities in the high-frequency (HF) and low-frequency (LF) band were calculated. Results: Patients with CFS were divided into those who screened positive for TMD (n = 16, 31%; CFS + TMD) and those who did not (n = 35, 69%; CFS − TMD). Both CFS groups had significantly higher self-rated ANS dysfunction than controls. CFS + TMD scored higher than CFS − TMD on the orthostatic and vasomotor subscales. The CFS + TMD group had significantly higher HF and significantly lower LF at rest than the other two groups. In discriminant function analysis, self-report orthostatic intolerance and HF units correctly classified 75% of participants. Conclusions: Almost one-third of CFS patients screened positive for TMD and this was associated with greater evidence of parasympathetic dysfunction. The presence of TMD shows potential as an effective screen for patients with CFS showing an autonomic profile and could help identify subgroups to target for treatment.

Chronic Fatigue Syndrome and DNA Hypomethylation of the Glucocorticoid Receptor Gene Promoter 1F Region: Associations With HPA Axis Hypofunction and Childhood Trauma.

Chronic fatigue syndrome (CFS) has been associated with hypothalamic-pituitary-adrenal axis hypofunction and enhanced glucocorticoid receptor (GR) sensitivity. In addition, childhood trauma is considered a major risk factor for the syndrome. This study examines DNA methylation of the GR gene (NR3C1) in CFS and associations with childhood sexual and physical trauma. Quantification of DNA methylation within the 1F promoter region of NR3C1 was performed in 76 female patients (46 with no/mild and 30 with moderate/severe childhood trauma) and 19 healthy controls by using Sequenom EpiTYPER. Further, we examined the association of NR3C1-1F promoter methylation with the outcomes of the low-dose (0.5 mg) dexamethasone/corticotropin-releasing factor test in a subset of the study population. Mann-Whitney U tests and Spearman correlations were used for statistical analyses. Overall NR3C1-1F DNA methylation was lower in patients with CFS than in controls. After cytosine guanine dinucleotide (CpG)-specific analysis, CpG_1.5 remained significant after Bonferroni correction (adjusted p = .0014). Within the CFS group, overall methylation (ρ = 0.477, p = .016) and selective CpG units (CpG_1.5: ρ = 0.538, p = .007; CpG_12.13: ρ = 0.448, p = .025) were positively correlated with salivary cortisol after dexamethasone administration. There was no significant difference in NR3C1-1F methylation between traumatized and nontraumatized patients. We found evidence of NR3C1 promoter hypomethylation in female patients with CFS and the functional relevance of these differences was consistent with the hypothalamic-pituitary-adrenalaxis hypofunction hypothesis (GR hypersuppression). However, we found no evidence of an additional effect of childhood trauma on CFS via alterations in NR3C1 methylation.