Chronic Fatigue Syndrome: Chalder T

Deary V, Chalder T, Sharpe M. · Institute of Health and Society, University of Newcastle, 21 Claremont Place, Newcastle Upon Tyne NE2 4AA, UK. · Clin Psychol Rev. · Pubmed #17822818 No free full text.

Abstract: The article is a narrative review of the theoretical standing and empirical evidence for the cognitive behavioural model of medically unexplained symptoms (MUS) in general and for chronic fatigue syndrome (CFS) and irritable bowel syndrome (IBS) in particular. A literature search of Medline and Psychinfo from 1966 to the present day was conducted using MUS and related terms as search terms. All relevant articles were reviewed. The search was then limited in stages, by cognitive behavioural therapy (CBT), condition, treatment and type of trial. Evidence was found for genetic, neurological, psychophysiological, immunological, personality, attentional, attributional, affective, behavioural, social and inter-personal factors in the onset and maintenance of MUS. The evidence for the contribution of individual factors, and their autopoietic interaction in MUS (as hypothesised by the cognitive behavioural model) is examined. The evidence from the treatment trials of cognitive behavioural therapy for MUS, CFS and IBS is reviewed as an experimental test of the cognitive behavioural models. We conclude that a broadly conceptualized cognitive behavioural model of MUS suggests a novel and plausible mechanism of symptom generation and has heuristic value. We offer suggestions for further research.

Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. · St Mary's Hospital, London, UK. · Clin Evid. · Pubmed #16620458 No free full text.

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Elena Garralda M, Chalder T. · Imperial College, London, UK. · J Child Psychol Psychiatry. · Pubmed #16238661 No free full text.

Abstract: BACKGROUND: Chronic fatigue syndrome (CFS) is being increasingly recognized in children and adolescents. Yet comparatively little attention has been given in the literature to management. METHODS: Description of the main features of the disorder, precipitating and maintaining factors and diagnostic assessment. Outline of different views on the nature and treatment of CFS in childhood. Description of a rehabilitation program based on cognitive behavior therapy and graded activity. RESULTS: Using adult research criteria, CFS can be diagnosed in children and adolescents. In its severe form it is often triggered by infectious illness episodes. It is commonly associated with mood disorders in the child and with mental distress and high levels of emotional involvement in parents. A number of patient support groups hold the view that CFS is a medical disorder, contest a psychiatric contribution and advocate 'pacing' as an approach to rehabilitation which includes avoiding activities. To date there is no empirical evidence for the efficacy of this approach. Research in adults, open and clinical reports in children support the use of graded activity and family cognitive behavior therapy. The main aim is to enable children, with the help of their family, to carry out their own rehabilitation with some support and guidance from a health professional. Engaging the child and family in treatment and forming a therapeutic alliance is a continual process and a crucial aspect of management, as many families view the condition as a medical disorder and are initially ambivalent towards this approach. CONCLUSIONS: There is controversy about the nature and management of CFS in childhood but a rehabilitation program based on family cognitive behavior therapy can be implemented and seems to hold most promise in the management of children with CFS. Family engagement is a crucial aspect of management.

Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. · St Mary's Hospital, London, UK. · Clin Evid. · Pubmed #15865734 No free full text.

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Rimes KA, Chalder T. · Department of Psychological Medicine, Institute of Psychiatry, London, UK. · Occup Med (Lond). · Pubmed #15699088 No free full text.

Abstract: AIMS: To review studies evaluating the treatment of chronic fatigue and chronic fatigue syndrome, to describe predictors of response to treatment and to discuss the role of the occupational health physician. METHODS: A literature search was carried out using Medline and PsychInfo. RESULTS: Studies evaluating cognitive behaviour therapy, graded exercise therapy, pharmacological interventions (e.g. antidepressants and corticosteroids), immunological interventions and nutritional supplements were reviewed. The most promising results have been found with cognitive behaviour therapy and graded exercise therapy, and some predictors of outcome have been identified. Most of the other interventions were evaluated in just one or two studies and therefore evidence is insufficient to draw firm conclusions. CONCLUSIONS: By applying the models of fatigue that form the bases for cognitive behaviour therapy and graded exercise therapy, occupational health physicians may play an important role in helping the patients with chronic fatigue syndrome to reduce their symptoms, improve their functioning and return to work.

Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. · St Mary's Hospital, London, UK. · Clin Evid. · Pubmed #15555147 No free full text.

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Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. · St Mary's Hospital, London, UK. · Clin Evid. · Pubmed #12603930 No free full text.

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Candy B, Chalder T, Cleare AJ, Wessely S, White PD, Hotopf M. · Department of Psychological Medicine, Guy's, King's and St. Thomas' School of Medicine, London. · Br J Gen Pract. · Pubmed #12392128 links to  free full text

Abstract: Infectious mononucleosis is usually an acute, transiently incapacitating condition, but for some sufferers it precipitates chronic illness. It is unclear which patients are at risk of a prolonged state of illness following onset of infectious mononucleosis and if there are any useful preventive measures that would facilitate recovery. The aim of this study was to review all cohort studies and intervention trials that provide information on: (a) the longitudinal course of ill health subsequent to the onset of infectious mononucleosis; (b) the relationship between psychosocial and clinical factors and recovery rate; and (c) the effect of interventions on recovery. A systematic review was conducted, based on a search of the PSYCHINFO, MEDLINE, EMBASE and CINHAL databases up to October 2001, and ISI Science and Social Sciences Citation Indices up to 22 November 2001. Eight papers were identified that gave data on illness following onset of infectious mononucleosis. The best evidence concluded that there is a distinct fatigue syndrome after infectious mononucleosis. Eight papers explored risk factors for prolonged illness following acute infectious mononucleosis. Results varied on the association of acute illness characteristics and psychological features with prolonged ill health. Poor physical functioning, namely lengthy convalescence and being less fit or active, consistently predicted chronic ill health. Three trials reported on interventions that aimed to shorten the time taken to resolve symptoms after uncomplicated infectious mononucleosis. None of the drug trials found any evidence that drug therapy shortens recovery time. The trial that compared the effect of activity with imposed bed rest, found that those patients allowed out of bed as soon as they felt able reported a quicker recovery. More information is needed on the course of ill health subsequent to the onset of infectious mononucleosis. Certain risk factors associated with delay may be amenable to a simple intervention in primary care.

Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. · Guy's, King's and St Thomas' School of Medicine, Institute of Psychiatry, London, UK. · Clin Evid. · Pubmed #12230719 No free full text.

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Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. · Guy's, Kings, and St Thomas's School of Medicine and Institute of Psychiatry, London SE5 8AZ. · BMJ. · Pubmed #10650029 links to  free full text

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Candy B, Chalder T, Cleare AJ, Wessely S, Hotopf M. · Department of Psychological Medicine, Guy's, King's and St. Thomas' School of Medicine, 103 Denmark Hill, London SE5 8AZ, UK. · J Psychosom Res. · Pubmed #15256300 No free full text.

Abstract: OBJECTIVES: Glandular fever is associated with an approximate fivefold increase in fatigue at 6 months. Reduced levels of fitness and illness beliefs may be important predictors of fatigue following glandular fever. We therefore developed a brief psycho-educational intervention aimed at improving recovery from infectious mononucleosis, and piloted a randomised controlled trial to evaluate the intervention. METHODS: We performed a randomised-controlled trial in primary health care in Southeast London and Kent. Sixty-nine patients aged between 16 and 45 years who were diagnosed, serologically and clinically, with acute infectious mononucleosis between December 1999 and December 2000 were randomised. The control group received a standardised fact-sheet about infectious mononucleosis, which gave no advice on rehabilitation. Patients who were randomised to the intervention received an individual treatment session, two follow-up telephone calls, and an information booklet. Fatigue score 6 months after the onset of infectious mononucleosis was the main outcome measure. RESULTS: Sixty-nine out of 139 patients referred were recruited and randomised. Eighty-seven percent of those recruited completed the Fatigue Questionnaire at 6 months. The intervention was acceptable to all who received it. There were fewer fatigue cases in the intervention group than the control group at 6 months follow-up (odds ratio 0.31, 95% confidence interval 0.09-0.91). CONCLUSIONS: A brief intervention at the diagnosis of infectious mononucleosis is acceptable, and may help prevent the development of chronic fatigue. Definitive randomised controlled trials are required to test the intervention.

Chalder T, Godfrey E, Ridsdale L, King M, Wessely S. · Department of Psychological Medicine, Guy's, King's and St Thomas's School of Medicine, London. · Psychol Med. · Pubmed #12622306 No free full text.

Abstract: BACKGROUND: The objective of this study was to examine factors that predicted outcome in a chronically fatigued group of patients who were randomized to cognitive behaviour therapy or counselling in primary care. METHOD: Illness perceptions, attributions, fatigue, disability and demographic variables were recorded at assessment and levels of fatigue and disability were measured at 6 months post randomization. Logistic regression was used to examine associations. RESULTS: Factors that predicted a poor outcome (four or more on the fatigue questionnaire) were: poor social adjustment at assessment; the patients self-report that they had never seen the GP for an emotional reason; a physical illness attribution; and, a long perceived future illness duration. CONCLUSIONS: Patients who are more psychologically minded are more likely to improve with psychological treatments in primary care. General practitioners need to assess this before referring to an appropriate therapist.

Deale A, Husain K, Chalder T, Wessely S. · Academic Department of Psychological Medicine, Guy's, King's, and St. Thomas's School of Medicine, London, UK. · Am J Psychiatry. · Pubmed #11729022 links to  free full text

Abstract: OBJECTIVE: This study evaluated the long-term outcome of cognitive behavior therapy versus relaxation therapy for patients with chronic fatigue syndrome. METHOD: Sixty patients who participated in a randomized controlled trial of cognitive behavior therapy versus relaxation therapy for chronic fatigue syndrome were invited to complete self-rated measures and participate in a 5-year follow-up interview with an assessor who was blind to treatment type. RESULTS: Fifty-three patients (88%) participated in the follow-up study: 25 received cognitive behavior therapy and 28 received relaxation therapy. A total of 68% of the patients who received cognitive behavior therapy and 36% who received relaxation therapy rated themselves as "much improved" or "very much improved" at the 5-year follow-up. Significantly more patients receiving cognitive behavior therapy, in relation to those in relaxation therapy, met criteria for complete recovery, were free of relapse, and experienced symptoms that had steadily improved or were consistently mild or absent since treatment ended. Similar proportions were employed, but patients in the cognitive behavior therapy group worked significantly more mean hours per week. Few patients crossed the threshold for "normal" fatigue, despite achieving a good outcome on other measures. Cognitive behavior therapy was positively evaluated and was still used by over 80% of the patients. CONCLUSIONS: Cognitive behavior therapy for chronic fatigue syndrome can produce some lasting benefits but is not a cure. Once therapy ends, some patients have difficulty making further improvements. In the future, attention should be directed toward ensuring that gains are maintained and extended after regular treatment ends.

Ridsdale L, Godfrey E, Chalder T, Seed P, King M, Wallace P, Wessely S, Anonymous00230. · Department of General Practice, Guy's, King's and St Thomas's School of Medicine, King's College, 5 Lambeth Walk, London SE11 6SP. · Br J Gen Pract. · Pubmed #11271868 links to  free full text

Abstract: BACKGROUND: Fatigue is a common symptom for which patients consult their doctors in primary care. With usual medical management the majority of patients report that their symptoms persist and become chronic. There is little evidence for the effectiveness of any fatigue management in primary care. AIM: To compare the effectiveness of cognitive behaviour therapy (CBT) with counselling for patients with chronic fatigue and to describe satisfaction with care. DESIGN OF STUDY: Randomised trial with parallel group design. SETTING: Ten general practices located in London and the South Thames region of the United Kingdom recruited patients to the trial between 1996 and 1998. Patients came from a wide range of socioeconomic backgrounds and lived in urban, suburban, and rural areas. METHOD: Data were collected before randomisation, after treatment, and six months later. Patients were offered six sessions of up to one hour each of either CBT or counselling. Outcomes include: self-report of fatigue symptoms six months later, anxiety and depression, symptom attributions, social adjustment and patients' satisfaction with care. RESULTS: One hundred and sixty patients with chronic fatigue entered the trial, 45 (28%) met research criteria for chronic fatigue syndrome; 129 completed follow-up. All patients met Chalder et al's standard criteria for fatigue. Mean fatigue scores were 23 on entry (at baseline) and 15 at six months' follow-up. Sixty-one (47%) patients no longer met standard criteria for fatigue after six months. There was no significant difference in effect between the two therapies on fatigue (1.04 [95% CI = -1.7 to 3.7]), anxiety and depression or social adjustment outcomes for all patients and for the subgroup with chronic fatigue syndrome. Use of antidepressants and consultations with the doctor decreased after therapy but there were no differences between groups. CONCLUSION: Counselling and CBT were equivalent in effect for patients with chronic fatigue in primary care. The choice between therapies can therefore depend on other considerations, such as cost and accessibility.

Godfrey E, Cleare A, Coddington A, Roberts A, Weinman J, Chalder T. · Department of Psychology, Kings College London, London, UK. · J Psychosom Res. · Pubmed #19616144 No free full text.

Abstract: OBJECTIVE: This cross-sectional study aimed to measure the discrepancy between actual and perceived IQ in a sample of adolescents with CFS compared to healthy controls. We hypothesized that adolescents with CFS and their parent would have higher expectations of the adolescent's intellectual ability than healthy adolescents and their parent. METHODS: The sample was 28 CFS patients and 29 healthy controls aged 11-19 years and the parent of each participant. IQ was assessed using the AH4 group test of general intelligence and a self-rating scale which measured perceived IQ. RESULTS: Parents' perceptions of their children's IQ were significantly higher for individuals with CFS than healthy controls. CONCLUSIONS: High expectations may need to be addressed within the context of treatment.

Reid SF, Chalder T, Cleare A, Hotopf M, Wessely S. · Imperial College, St Mary's Hospital, London, UK. · Clin Evid (Online). · Pubmed #19445810 No free full text.

Abstract: INTRODUCTION: Chronic fatigue syndrome (CFS) affects between 0.006% and 3% of the population depending on the criteria of definition used, with women being at higher risk than men. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for chronic fatigue syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (BMJ Clinical evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressants, cognitive behavioural therapy (CBT), corticosteroids, dietary supplements, evening primrose oil, galantamine, graded exercise therapy, homeopathy, immunotherapy, intramuscular magnesium, oral nicotinamide adenine dinucleotide, and prolonged rest.

Roberts AD, Papadopoulos AS, Wessely S, Chalder T, Cleare AJ. · King's College London, Institute of Psychiatry, Department of Psychological Medicine, De Crespigny Park, London SE5 8AF, UK. · J Affect Disord. · Pubmed #18937978 No free full text.

Abstract: BACKGROUND: There is evidence that patients with chronic fatigue syndrome (CFS) have mild hypocortisolism. One theory about the aetiology of this hypocortisolism is that it occurs late in the course of CFS via factors such as inactivity, sleep disturbance, chronic stress and deconditioning. We aimed to determine whether therapy aimed at reversing these factors--cognitive behavioural therapy for CFS--could increase cortisol output in CFS. METHODS: We measured diurnal salivary cortisol output between 0800 and 2000 h before and after 15 sessions (or 6 months) of CBT in 41 patients with CDC-defined CFS attending a specialist, tertiary outpatient clinic. RESULTS: There was a significant clinical response to CBT, and a significant rise in salivary cortisol output after CBT. LIMITATIONS: We were unable to control for the passage of time using a non-treated CFS group. CONCLUSIONS: Hypocortisolism in CFS is potentially reversible by CBT. Given previous suggestions that lowered cortisol may be a maintaining factor in CFS, CBT offers a potential way to address this.

Caseras X, Mataix-Cols D, Rimes KA, Giampietro V, Brammer M, Zelaya F, Chalder T, Godfrey E. · Unitat de Psicologia Mèdica, Institut de Neurociències, Universitat Autònoma de Barcelona, Catalonia, Spain. · Psychol Med. · Pubmed #18447963 No free full text.

Abstract: BACKGROUND: Fatigue is the central symptom in chronic fatigue syndrome (CFS) and yet very little is known about its neural correlates. The aim of this study was to explore the functional brain response, using functional magnetic resonance imaging (fMRI), to the imaginal experience of fatigue in CFS patients and controls. METHOD: We compared the blood oxygen level dependent (BOLD) responses of 12 CFS patients and 11 healthy controls to a novel fatigue provocation procedure designed to mimic real-life situations. A non-fatiguing anxiety-provoking condition was also included to control for the non-specific effects of negative affect. RESULTS: During the provocation of fatigue, CFS patients reported feelings of both fatigue and anxiety and, compared to controls, they showed increased activation in the occipito-parietal cortex, posterior cingulate gyrus and parahippocampal gyrus, and decreased activation in dorsolateral and dorsomedial prefrontal cortices. The reverse pattern of findings was observed during the anxiety-provoking scenarios. CONCLUSIONS: The results may suggest that, in CFS patients, the provocation of fatigue is associated with exaggerated emotional responses that patients may have difficulty suppressing. These findings are discussed in relation to the cognitive-behavioural model of CFS.

Godfrey E, Chalder T, Ridsdale L, Seed P, Ogden J. · Department of Psychology, Institute of Psychiatry, Kings College London, UK. · Br J Clin Psychol. · Pubmed #17697477 No free full text.

Abstract: OBJECTIVES: To develop a brief measure of the therapy process and use it to examine which therapeutic ingredients were associated with outcome in a sample of patients from a randomized controlled trial (RCT) of cognitive behaviour therapy (CBT) versus counselling for patients with chronic fatigue in primary care. It was hypothesized that the two therapies would be clearly distinguishable and that in terms of process variables, the therapeutic alliance would be important in predicting outcome. DESIGN: The data for this study were collected alongside a RCT in primary care and included audiotaped therapy sessions. These tapes were assessed by two independent raters using a newly devised measure in order to evaluate therapy process and its relationship with outcome. METHODS: Tapes from 71 patients participating in the RCT were assessed to form the basis of the process analysis. Outcome was self-reported fatigue symptoms at 6 months follow-up. Data reduction was achieved via a principal component analysis (PCA). Factors were entered into a multiple regression analysis to produce a final model of predictors of outcome. RESULTS: The process measure showed that although the treatments could be distinguished, there was some overlap between them. The key predictor of a good fatigue outcome was emotional processing, including the expression, acknowledgement and acceptance of emotional distress. CONCLUSION: A new process measure was developed successfully which now warrants further testing. It was able to assess treatment adherence and unpack, and distinguish the common factor which predicted outcome across therapy modalities. The findings lend preliminary support to the view that the specific techniques associated with particular 'brand names' of therapy are not necessarily the 'active ingredients' that help patient's change within the primary care setting. Emotional processing predicted outcome for patients with chronic fatigue and therefore future research might explore this in more depth, in order to understand better how it can be facilitated.

Martin A, Chalder T, Rief W, Braehler E. · Section for Clinical Psychology and Psychotherapy, Philipps University, Marburg, Germany. · J Psychosom Res. · Pubmed #17662751 No free full text.

Abstract: OBJECTIVE: The objective of this study was to assess the prevalence of chronic fatigue (CF) and its association with somatization syndrome [Somatization Syndrome Index (SSI) 4/6: >/=4 somatoform symptoms in men, 6 in women] in the general population. METHODS: A representative sample of the German population (N=2412) completed a fatigue questionnaire and a screening instrument for current somatoform symptoms (Screening for Somatoform Symptoms 7). RESULTS: The prevalence rate of CF was 6.1% (n=147). Females were affected significantly more often as compared with males (7% vs. 5.1%). The mean number of somatoform symptoms was higher in CF cases than in control subjects without CF (11 vs. 2; P<.001). Seventy-two percent of the subjects with CF fulfilled the SSI4/6 criterion for somatization syndrome. Quality of life (EUROHIS-QOL and 8-item Short-Form Health Survey) and well-being (5-item WHO Well-Being Index) were markedly decreased in CF and SSI4/6. The results of regression analyses suggest that fatigue and somatization severity had a similar impact on quality of life. CONCLUSIONS: The results suggest that CF is relevant in the general population. Its substantial overlap with somatization syndrome supports the hypothesis that the two syndromes are only partially different manifestations of the same underlying processes.

White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R, Anonymous00373. · Department of Psychological Medicine, Queen Mary School of Medicine and Dentistry, St Bartholomew's Hospital, London, UK. <> · BMC Neurol. · Pubmed #17397525 links to  free full text

Abstract: BACKGROUND: Chronic fatigue syndrome (CFS, also called myalgic encephalomyelitis /encephalopathy or ME) is a debilitating condition with no known cause or cure. Improvement may occur with medical care and additional therapies of pacing, cognitive behavioural therapy and graded exercise therapy. The latter two therapies have been found to be efficacious in small trials, but patient organisations surveys have reported adverse effects. Although pacing has been advocated by patient organisations, it lacks empirical support. Specialist medical care is commonly provided but its efficacy when given alone is not established. This trial compares the efficacy of the additional therapies when added to specialist medical care against specialist medical care alone. METHODS: 600 patients, who meet operationalised diagnostic criteria for CFS, will be recruited from secondary care into a randomised trial of four treatments, stratified by current co morbid depressive episode and different CFS/ME criteria. The four treatments are standardised specialist medical care either given alone, or with adaptive pacing therapy or cognitive behaviour therapy or graded exercise therapy. Supplementary therapies will involve fourteen sessions over 23 weeks and a booster session at 36 weeks. Outcome will be assessed at 12, 24, and 52 weeks after randomisation. Two primary outcomes of self-rated fatigue and physical function will assess differential effects of each treatment on these measures. Secondary outcomes include adverse events and reactions, subjective measures of symptoms, mood, sleep and function and objective measures of physical activity, fitness, cost-effectiveness and cost-utility. The primary analysis will be based on intention to treat and will use logistic regression models to compare treatments. Secondary outcomes will be analysed by repeated measures analysis of variance with a linear mixed model. All analyses will allow for stratification factors. Mediators and moderators will be explored using multiple linear and logistic regression techniques with interactive terms, with the sample split into two to allow validation of the initial models. Economic analyses will incorporate sensitivity measures. DISCUSSION: The results of the trial will provide information about the benefits and adverse effects of these treatments, their cost-effectiveness and cost-utility, the process of clinical improvement and the predictors of efficacy.

Rimes KA, Goodman R, Hotopf M, Wessely S, Meltzer H, Chalder T. · King's College London, Institute of Psychiatry, Section of General Hospital Psychiatry, Weston Education Centre, Cutcombe Rd, London SE5 9RJ, United Kingdom. · Pediatrics. · Pubmed #17332180 links to  free full text

Abstract: OBJECTIVE: The objective of this study was to describe the incidence, prevalence, risk factors, and prognosis of fatigue, chronic fatigue, and chronic fatigue syndrome in 11- to 15-year-olds. METHODS: A random general population sample (n = 842) of British adolescents and their parents were assessed at baseline and 4 to 6 months later. The main outcomes were fatigue, chronic fatigue, and chronic fatigue syndrome, operationally defined. RESULTS: The incidence over 4 to 6 months was 30.3% for fatigue, 1.1% for chronic fatigue, and 0.5% for chronic fatigue syndrome. The point prevalence was 34.1% and 38.1% for fatigue, 0.4% and 1.1% for chronic fatigue, and 0.1% and 0.5% for chronic fatigue syndrome at time 1 and time 2, respectively. Of participants who were fatigued at time 1, 53% remained fatigued at time 2. The 3 cases of chronic fatigue and 1 case of chronic fatigue syndrome at time 1 had recovered by time 2. Higher risk for development of chronic fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and maternal distress; in multivariate analysis, baseline anxiety or depression remained a significant predictor of chronic fatigue. Increased risk for development of fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and older age; in multivariate analyses, these factors and female gender all were significant predictors of fatigue. CONCLUSIONS: The incidence rates for chronic fatigue and chronic fatigue syndrome in this adolescent sample were relatively high, but the prognosis for these conditions was good. This prospective study provides evidence for an association between emotional/behavioral problems and subsequent onset of fatigue/chronic fatigue.

Caseras X, Mataix-Cols D, Giampietro V, Rimes KA, Brammer M, Zelaya F, Chalder T, Godfrey EL. · Unitat de Psicologia Mèdica, Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain. · Psychosom Med. · Pubmed #17079703 links to  free full text

Abstract: OBJECTIVE: Up to 90% of patients with chronic fatigue syndrome (CFS) report substantial cognitive difficulties. However, objective evidence supporting these claims is inconsistent. The present functional magnetic resonance imaging study examined the neural correlates of working memory in patients with CFS compared with controls. METHODS: Seventeen patients with CFS and 12 healthy control subjects were scanned while performing a parametric version of the n-back task (0-, 1-, 2-, and 3-back). RESULTS: Both groups performed comparably well and activated the verbal working memory network during all task levels. However, during the 1-back condition, patients with CFS showed greater activation than control subjects in medial prefrontal regions, including the anterior cingulate gyrus. Conversely, on the more challenging conditions, patients with CFS demonstrated reduced activation in dorsolateral prefrontal and parietal cortices. Furthermore, on the 2- and 3-back conditions, patients but not control subjects significantly activated a large cluster in the right inferior/medial temporal cortex. Trend analyses of task load demonstrated statistically significant differences in brain activation between the two groups as the demands of the task increased. CONCLUSIONS: These results suggest that patients with CFS show both quantitative and qualitative differences in activation of the working memory network compared with healthy control subjects. It remains to be determined whether these findings stay stable after successful treatment.

Quarmby L, Rimes KA, Deale A, Wessely S, Chalder T. · King's College London, Academic Department of Psychological Medicine, Weston Education Centre, Cutcombe Road, London SE5 9RJ, UK. · Behav Res Ther. · Pubmed #17074300 No free full text.

Abstract: Outcomes for cognitive-behaviour therapy (CBT) in randomised controlled trials (RCTs) have rarely been compared to those in routine clinical practice. Taking the case of CBT for chronic fatigue syndrome (CFS), we evaluated the results of a successful RCT against those of the same treatment given in the same setting as part of routine practice. Fatigue and social adjustment scores were compared for patients who received CBT for CFS as part of a RCT (N=30) and patients who received CBT as part of everyday clinical practice (N=384). The results in the RCT were superior to those in routine clinical practice. Between pre-treatment and 6-month follow-up, the RCT showed a larger reduction in fatigue and greater improvement in social adjustment than those in routine treatment. The changes in fatigue scores were similar for both groups during treatment but were greater in the RCT between post-treatment and follow-up. Potential reasons for the superior results of the RCT include patient selection, therapist factors and the use of a manualised treatment protocol. Practitioners need to pay particular attention to relapse prevention and ensuring adequate follow-up in addition to encouraging patients to continue with cognitive-behavioural strategies once treatment has ended.

Roberts AD, Wessely S, Chalder T, Papadopoulos A, Cleare AJ. · Section of General Hospital Psychiatry, Division of Psychological Medicine, Guy's, King's and St Thomas' School of Medicine and Dentistry, London, UK. · Br J Psychiatry. · Pubmed #14754825 links to  free full text

Abstract: BACKGROUND: There is accumulating evidence of hypothalamic-pituitary-adrenal (HPA) axis disturbances in chronic fatigue syndrome (CFS). The salivary cortisol response to awakening has been described recently as a non-invasive test of the capacity of the HPA axis to respond to stress. The results of this test correlate closely with those of more invasive dynamic tests reported in the literature; furthermore, it can be undertaken in a naturalistic setting. AIMS: To assess the HPA axis using the salivary cortisol response to awakening in CFS. METHOD: We measured salivary cortisol upon awakening and 10, 20, 30 and 60 min afterwards in 56 patients with CFS and 35 healthy volunteers. RESULTS: Patients had a lower cortisol response to awakening, measured by the area under the curve. CONCLUSIONS: This naturalistic test of the HPA axis response to stress showed impaired HPA axis function in CFS.