Fatigue syndromes: a comparison of chronic "postviral" fatigue with neuromuscular and affective disorders.

Patients (n = 47) presenting to a neurological centre with unexplained chronic "postviral" fatigue (CFS) were studied prospectively. Controls were patients with peripheral fatiguing neuromuscular diseases and inpatients with major depression in a psychiatric hospital. Seventy-two percent of the CFS patients were cases of psychiatric disorder, using criteria that excluded fatigue as a symptom, compared with 36% of the neuromuscular group. There was no difference in subjective complaints of physical fatigue between all groups. Mental fatigue and fatigability was equally common in CFS and affective patients, but only occurred in those neuromuscular patients who were also cases of psychiatric disorder. Overall, the CFS patients more closely resembled the affective than the neuromuscular patients. Attribution of symptoms to physical rather than psychological causes was the principal difference between matched CFS and psychiatric controls. The symptoms of "postviral" fatigue had little ability to discriminate between CFS and affective disorder. The fatigue in CFS appeared central in origin, suggesting it is not primarily a neuromuscular illness. The implications for research and treatment of chronic fatigue are discussed.     

Illness experience,depression, and anxiety in chronic fatigue syndrome

Objective: Given the high rate of psychiatric comorbidity with chronic fatigue syndrome (CFS), we considered two possible correlates of anxiety and depression: lack of illness legitimization and beliefs about limiting physical activity. Method: A total of 105 people diagnosed with CFS reported on their experiences with medical professionals and their beliefs about recovery and completed the depression and anxiety subscales of the Brief Symptom Inventory. Results: Those who said that their physician did not legitimize their illness (36%) had higher depression and anxiety scores (P's<.05) than their counterparts. Those who believed that limiting their physical exertion was the path to recovery (55%) had lower depression and anxiety scores (P's<.01) than their counterparts. Conclusion: Lack of illness legitimization ranked high as a source of dissatisfaction for CFS patients, and it may aggravate psychiatric morbidity. Many CFS patients believed that staying within what they felt to be their physical limits would improve their condition. This belief, and possibly an accompanying sense of control over their symptoms, may alleviate psychiatric morbidity.     

Illness perceptions and mood in chronic fatigue syndrome

BACKGROUND: Individual beliefs and cognitions may affect adjustment to chronic fatigue syndrome (CFS) and illness perceptions, in particular, have been reported to correlate with both disability and psychological adjustment to CFS in self-diagnosed cases. OBJECTIVES: The aim of the present study was to examine these relationships in a clinic sample of CFS patients assessed by both a physician and psychiatrist. METHOD: A sample of 173 patients referred to a multidisciplinary CFS clinic and fulfilling current operational criteria for CFS [Ann Intern Med 121 (1994) 953; J R Soc Med 84 (1991) 118.] were randomly selected from the clinic database and surveyed with the Hospital Anxiety and Depression scale, Fatigue Questionnaire and Illness Perceptions Questionnaire [J Psychosom Res 37 (1993) 147; Psychol Health 11 (1996) 431; Acta Psychiatr Scand 67 (1983) 361.]. RESULTS: A total of 126 patients responded (73% response rate). The illness perception components studied were consequences (of illness), illness identity, causes (of illness), the ability to control/cure the illness and (expected) timeline of the illness. These components accounted for 15%, 28% and 30% of the variance in levels of fatigue, depression and anxiety, respectively. Two of the illness perception components (consequences and illness identity) were stronger predictors of fatigue score than mood scores. CONCLUSIONS: These findings confirmed in a clinical sample that illness perceptions are associated with variation in both disability and psychological adjustment in CFS. Illness perceptions may have an important and long-lasting effect on adaptation to CFS, and it is necessary to have a greater understanding of their role in order to tailor effective interventions for the condition.     

Psychiatric morbidity in the chronic fatigue syndrome: are patients with personality disorder more physically impaired?

OBJECTIVE: The long-term consequences of chronic fatigue syndrome (CFS) include substantial impairment in physical functioning and high levels of work disability. In the absence of a medical explanation for this impairment, some have speculated that it may be due to comorbid psychiatric illness or personality disorder. We addressed this possibility by comparing the functional status of three CFS groups: no psychiatric diagnosis, psychiatric illness only, psychiatric illness and personality disorder. A second aim of the study was to determine whether a continuous measure of psychological distress could provide a better account of impairment than psychiatric diagnosis. METHOD: The study sample consisted of 84 consecutive female referrals with CFS. All participants satisfied the case definition and completed an assessment protocol consisting of: physical examination, psychiatric interview and self-report questionnaires. RESULTS: Psychiatric illness, either alone or in combination with a comorbid personality disorder, was not associated with physical impairment or disability in female participants. A regression model of physical functioning found that psychological distress accounted for 6% and symptom severity for 41% of the variance (P=.06 and <.01, respectively). In the case of disability, the corresponding percentages were 2% and 18% (NS and P<.01, respectively). The modest effects of psychological distress could not be attributed to symptom severity. CONCLUSIONS: Although psychiatric illness and personality disorder was prevalent, neither could explain the effects of CFS on physical functioning and disability. As yet, there is no psychological or medical explanation for the behavioral consequences of CFS.     

Chronic fatigue syndrome of childhood

OBJECTIVE: To examine clinical specificity in chronic fatigue syndrome (CFS) of childhood, by comparing clinical features in childhood CFS and in emotional disorders (ED). METHOD SAMPLE: 28 children with CFS; 27 with ED. MEASURES: History of disorder; K-SADS psychiatric interviews; self-esteem and physical symptoms questionnaires; premorbid history, behavioural and personality assessments. RESULTS: There were high levels of comorbid emotional disorders in children with CFS, and the two groups were comparable on self-esteem, but CFS children endorsed more fatigue and other somatic symptoms. The two groups were comparable on age at illness onset, but parents of children with CSF reported more biological illness precipitants, more pre-morbid recurrent medical problems and infections. The CFS group had fewer pre-morbid psychological problems and less psychiatric comorbidity than the ED group. CONCLUSION: There is considerable clinical overlap between CFS and ED of childhood, but there are also differences in clinical presentation between these disorders.     

Psychiatric Aspects of Chronic Fatigue Syndrome and Fibromyalgia

Chronic fatigue syndrome and/or fibromyalgia (CFS/FM) consists of highly overlapping, medically unexplained symptoms, including long-lasting fatigue, effort intolerance, cognitive dysfunction, and widespread pain and tenderness. CFS/FM often seems to be triggered by infections and physical trauma, but depression, sleep disturbances, and personality may also be involved. Moreover, dysregulation of the stress system, the immune system, and central pain mechanisms may determine the pathophysiology of the illness, leading to a loss of capacity to adapt to all kind of stressors. CFS/FM patients can be best helped by a pragmatic and individualized approach aimed at adjusting lifestyle and optimizing self-care, which in the long run may contribute to a restoration of physical and mental adaptability. Future psychiatric research into CFS/FM should focus on the complex interrelationships among pain/fatigue, stress/depression, and personality, as well as on processes of therapeutic change and the advantages of customized treatment.     

Brain 5-HT1A receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY-100635.

BACKGROUND: Research from neuroendocrine challenge and other indirect studies has suggested increased central 5-HT function in chronic fatigue syndrome (CFS) and increased 5-HT1A receptor sensitivity. We assessed brain 5-HT1A receptor binding potential directly using the specific radioligand [11C]WAY-100635 and positron emission tomography (PET). METHODS: We selected 10 patients from a tertiary referral clinic who fulfilled the CDC consensus criteria for CFS. To assemble a homogenous group and avoid confounding effects, we enrolled only subjects who were completely medication-free and did not have current comorbid psychiatric illness. We also scanned 10 healthy control subjects. RESULTS: There was a widespread reduction in 5-HT1A receptor binding potential in CFS relative to control subjects. This was particularly marked in the hippocampus bilaterally, where a 23% reduction was observed. CONCLUSIONS: There is evidence of decreased 5-HT1A receptor number or affinity in CFS. This may be a primary feature of CFS, related to the underlying pathophysiology, or a finding secondary to other processes, such as previous depression, other biological changes or the behavioral consequences of CFS.     

Functional status,neuropsychological functioning,and mood in chronic fatigue syndrome (CFS): relationship to psychiatric disorder

Individuals with chronic fatigue syndrome (CFS) face chronic physical debilitation, reduced neuropsychological functioning, and changes in emotional well-being that significantly detract from quality of life. The role of psychiatric disturbance in reducing quality of life in CFS remains unclear. In the current investigation, the role of psychiatric status in reducing health-related quality of life in CFS was examined. Four subject groups were compared on measures of functional well-being, mood, and neuropsychological status: individuals with CFS and no history of psychiatric illness, individuals who had current symptoms of psychiatric illness that began after their CFS diagnosis, individuals who had current symptoms of psychiatric illness that began before their CFS diagnosis, and a healthy sedentary control group. Overall, it was found that individuals with CFS suffer from profound physical impairment. Concurrent psychiatric illness, however, did not adversely affect physical functional capacity. Physical functional capacity was not worse in individuals with a concurrent psychiatric illness. As expected, concurrent psychiatric illness was found to reduce emotional well-being. Moreover, individuals with a psychiatric illness that predated the onset of CFS suffered the greatest emotional distress. Thus, an individual's psychiatric history should be considered when attempting to understand the factors maintaining disability in CFS.     

Chronic fatigue syndrome: Reviewing the research findings

This article reviews the current state of research in chronic fatigue syndrome (CFS). The evolving definition, prevalence, and prognosis of this controversial illness are presented. We review studies examining psychiatric, personality, and psychosocial etiology for CFS. The evidence for pathophysiology in CFS is also presented, and studies investigating viral, immune, neuroimaging, neuroendocrine, and central and autonomic nervous system abnormalities in CFS are assessed. Current evidence indicates that CFS is multi-determined and heterogeneous and that subgrouping patients according to factors such as psychiatric state and symptom onset may be fruitful. The current state of treatment for CFS is reviewed, and the challenges for research aimed at resolving this prototypical mind/body problem are discussed.     

Psychological correlates of functional status in chronic fatigue syndrome

Background: The present study was designed to test a cognitive model of impairment in chronic fatigue syndrome (CFS) in which disability is a function of severity of fatigue and depressive symptoms, generalized somatic symptom attributions and generalized illness worry. Methods: We compared 45 CFS and 40 multiple sclerosis (MS) outpatients on measures of functional ability, fatigue severity, depressive symptoms, somatic symptom attribution and illness worry. Results: The results confirmed previous findings of lower levels of functional status and greater fatigue among CFS patients compared to a group of patients with MS. Fatigue severity was found to be a significant predictor of physical functioning but not of psychosocial functioning in both groups. In CFS, when level of fatigue was controlled, making more somatic attributions was associated with worse physical functioning, and both illness worry and depressive symptoms were associated with worse psychosocial functioning. Conclusions: Our findings support the role of depression and illness cognitions in disability in CFS sufferers. Different cognitive factors account for physical and psychosocial disability in CFS and MS. The SF-36 may be sensitive to symptom attributions, suggesting caution in its interpretation when used with patients with ill-defined medical conditions.     

Psychiatric adjustment in adolescents with a history of chronic fatigue syndrome

OBJECTIVE: To ascertain psychiatric adjustment in youngsters with a history of childhood chronic fatigue syndrome (CFS). METHOD: Subjects were 25 children and adolescents with CFS who were seen in tertiary pediatric/psychiatric clinics (mean age 15.6 years, seen a mean of 45.5 months after illness onset; 17 subjects had recovered and 8 were still ill) and 15 healthy matched controls. Youngsters and their parents (usually mothers) were interviewed and completed questionnaires. Instruments used included the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), the Child Behavior Checklist (CBCL), and the Harter Self-Esteem Questionnaire. RESULTS: At assessment, psychiatric disorders (mainly anxiety and depressive disorders) were present in half the subjects with a history of CFS, a rate significantly higher than in healthy controls. On the CBCL youngsters with a history of CFS had an excess of psychological symptoms and decreased social competence. On the Harter Self-Esteem Questionnaire they reported reduced self-esteem, especially in social competence. Anxiety disorders were significantly more common in recovered subjects than in those with active CFS illness status. CONCLUSIONS: Psychiatric disorders were found to be increased in adolescents with a history of severe CFS; CFS may enhance the risk for or share common predisposing factors with anxiety disorders.     

Objective assessment of personality disorder in chronic fatigue syndrome

OBJECTIVES: This study aims to objectively assess the prevalence and nature of personality disorders in depressed and nondepressed chronic fatigue syndrome (CFS) patients and compare this to depressed and healthy control groups. METHODS: Sixty-one patients attending a tertiary referral clinic with chronic fatigue syndrome, 40 psychiatric inpatients with depressive disorder and 45 healthy medical students completed the Structured Clinical Interview for DSM-III-R Diagnoses (SCID-II) in addition to providing routine clinical and demographic information. RESULTS: Thirty-nine percent of the CFS group, 73% of the depressed group and 4% of the healthy group were diagnosed with personality disorders. Cluster C disorders were the most common in both the CFS and depressed group. The depressed CFS patients had more Cluster B personality disorders than nondepressed CFS patients. Overall for CFS patients there was no association between mood state and personality disorder. CONCLUSIONS: High levels of personality disorder are found on objective assessment of CFS patients attending a teaching hospital clinic. This cannot be accounted for by comorbid depression.     

Differences between patients with chronic fatigue syndrome and with chronic fatigue at an infectious disease clinic in Stockholm,Sweden

Background data were collected from patients presenting with fatigue at the clinic of infectious diseases at Huddinge University Hospital, Stockholm. The main purpose was to look for differences as to demographic and functional status for patients fulfilling criteria for chronic fatigue syndrome (CFS) and chronic fatigue (CF). A cross-sectional questionnaire survey was performed using a variety of instruments. A thorough medical investigation was performed. No difference was found as to social situation, occupation and illness attributions for patients in the two categories. Patients with CFS reported in general a higher degree of 'sickness' with more self-reported somatic symptoms, more self-reported functional impairment and more absence from work. A higher degree of psychiatric comorbidity was observed in CF than in CFS patients. A majority of CFS patients (80%) had an acute infectious onset compared to 43% in the CF group. Presently used criteria might, according to findings presented here, define two different patient categories in a population characterized by severe, prolonged fatigue. Because CFS patients (compared to patients with CF) have more somatic symptoms, more often report an infectious, sudden onset and have less psychiatric comorbidity, and CF patients seem to have more of an emotional, burn-out-like component one could speculate about the existence of different pathogenetic backgrounds behind the two diagnoses.     

Screening for prolonged fatigue syndromes: validation of the SOFA scale

  Background: The identification of syndromes characterised by persistent and disabling mental and/or physical fatigue is of renewed interest in psychiatric epidemiology. This report details the development of two specific instruments: the SOFA/CFS for identification of patients with chronic fatigue syndrome (CFS) in specialist clinics and the SOFA/GP for identification of prolonged fatigue syndromes (PFS) in community and primary care settings. Methods: Patients with clinical diagnoses of CFS (n = 770) and consecutive attenders at primary care (n = 1593) completed various self-report questionnaires to assess severity of current fatigue-related symptoms and other common somatic and psychological symptoms. Quality receiver operating characteristic curves were used to derive appropriate cut-off scores for each of the instruments. Comparisons with other self-report measures of anxiety, depression and somatic distress are noted. Various multivariate statistical modelling techniques [latent class analysis (LCA), longitudinal LCA] were utilised to define the key features of PFS and describe its longitudinal characteristics. Results: The SOFA/CFS instrument performs well in specialist samples likely to contain a high proportion of patients with CFS disorders. Cut-off scores of either 1/2 or 2/3 can be used, depending on whether the investigators wish to preferentially emphasise false-negatives or false-positives. Patients from these settings can be thought of as consisting not only of those with a large number of unexplained medical symptoms, but also those with rather specific musculoskeletal and pain syndromes. The SOFA/GP instrument has potential cut-off scores of 1/2 or 2/3, with the latter preferred as it actively excludes all non-PFS cases (sensitivity = 81%, specificity = 100%). Patients with these syndromes in the community represent broader sets of underlying classes, with the emergence of not only musculoskeletal and multisymptomatic disorders, but also persons characterised by significant cognitive subjective impairment. Twelve-month longitudinal analyses of the primary care sample indicated that the underlying class structure was preserved over time. Comparisons with other measures of psychopathology indicated the relative independence of these constructs from conventional notions of anxiety and depression. Conclusions: The SOFA/GP instrument (which is considerably modified from the SOFA/CFS in terms of anchor points for severity and chronicity) is preferred for screening in primary care and community settings. Patients with PFS and CFS present a range of psychopathology that differs in its underlying structure, cross-sectionally and longitudinally, from coventional notions of anxiety and depression.     

Correlates of illness worry in chronic fatigue syndrome

BACKGROUND: Anxiety about illness leading to restriction of activity and physical deconditioning has been hypothesized to contribute to the chronicity of fatigue. Pathological symptom attributions, personality traits, and depression have all been hypothesized to contribute to illness worry. METHODS: We compared 45 chronic fatigue syndrome (CFS) and 40 multiple sclerosis (MS) outpatients using a battery of psychometric instruments comprising the 12-item Illness Worry scale, the Symptom Interpretation Questionnaire (SIQ), the NEO Five-Factor Inventory (NEO-FFI), and a modified version of the SCL-90R Depression scale. RESULTS: There was no difference between the two diagnostic groups on neuroticism, depressive symptoms, as well as the three scales of the SIQ. On the illness worry index, the CFS group had significantly higher scores than the MS group. This difference was due to items tapping vulnerability to illness and the perception that others are not taking their illness seriously. Somatic attributional style, neuroticism, depressive symptoms, and age were all significant predictors of illness worry in both CFS and MS patients. CONCLUSIONS: Somatic attributions, neuroticism, and depression all contribute to illness worry in chronic illness. However, these factors do not account for the higher levels of illness worry in CFS as opposed to MS, which may be due to other specific cognitive and social interactional processes.     

Generalized anxiety disorder in chronic fatigue syndrome

A structured psychiatric interview, forming part of a global psychopathological approach, revealed higher prevalence rates of current and lifetime psychiatric disorders and a higher degree of psychiatric comorbidity in patients with chronic fatigue syndrome (CFS) than in a medical control group. In contrast to previous studies, a very high prevalence of generalized anxiety disorder (GAD) was found in CFS, characterized by an early onset and a high rate of psychiatric comorbidity. It is postulated that GAD represents a susceptibility factor for the development of CFS. A significantly higher prevalence was also observed for the somatization disorder (SD) in the CFS group. Apart from a higher female-to-male ratio in fibromyalgia, no marked differences were observed in sociodemographic or illness-related features, or in psychiatric morbidity, between CFS patients with and without fibromyalgia. CFS patients with SD have a longer illness duration and a higher rate of psychiatric comorbidity. These findings are consistent with the suggestion of Hickie et al. (1) that chronic fatigued subjects with SD should be distinguished from subjects with CFS.     

The relation of sleep difficulties to fatigue, mood and disability in chronic fatigue syndrome

The relationship of sleep complaints to mood, fatigue, disability, and lifestyle was examined in 69 chronic fatigue syndrome (CFS) patients without psychiatric disorder, 58 CFS patients with psychiatric disorder, 38 psychiatric out-patients with chronic depressive disorders, and 45 healthy controls. The groups were matched for age and gender. There were few differences between the prevalence or nature of sleep complaints of CFS patients with or without current DSM-IIIR depression, anxiety or somatization disorder. CFS patients reported significantly more naps and waking by pain, a similar prevalence of difficulties in maintaining sleep, and significantly less difficulty getting off to sleep compared to depressed patients. Sleep continuity complaints preceded fatigue in only 20% of CFS patients, but there was a strong association between relapse and sleep disturbance. Certain types of sleep disorder were associated with increased disability or fatigue in CFS patients. Disrupted sleep appears to complicate the course of CFS. For the most part, sleep complaints are either attributable to the lifestyle of CFS patients or seem inherent to the underlying condition of CFS. They are generally unrelated to depression or anxiety in CFS.     

Attributions and self-esteem in depression and chronic fatigue syndromes

There is considerable overlap in symptomatology between chronic fatigue syndrome (CFS) and affective disorder. We report a comparison of depressive phenomenology and attributional style between a group of CFS subjects seen in a specialized medical setting, which included a high proportion with depression diagnosed by Research Diagnostic Criteria (RDC) and depressed controls seen in a specialized psychiatric setting. Significant symptomatic differences between the depressed CFS group and depressed controls were observed for features such as self-esteem and guilt as well as attribution of illness. All the CFS groups tended to attribute their symptoms to external causes whereas the depressed controls experienced inward attribution. This may have resulted from differences in the severity of mood disorder between the samples, but it is also suggested that an outward style of attribution protects the depressed CFS patients from cognitive changes associated with low mood but at the expense of greater vulnerability towards somatic symptoms such as fatigue.     

Predictors of outcome in fatigued employees on sick leave: results from a randomised trial

OBJECTIVE: The main objective of this study was to identify predictors of fatigue caseness, work resumption and chronic fatigue syndrome (CFS)-like caseness in a sample of fatigued employees on sick leave. METHODS: For 12 months, 151 fatigued employees on sick leave, 44% of whom met research criteria for CFS at baseline, were followed. Measures included fatigue, health aspects, psychological problems, burnout, causal attributions and self-efficacy. Logistic regression analysis was used to determine associations between predictor variables at baseline and outcome at follow-up. RESULTS: After 12 months, 43% of the patients were no longer fatigue cases, and 62% had resumed work. Recovery from fatigue caseness was predicted by stronger psychological attributions and other perception-related factors, whereas work resumption was predicted by lower age, male sex, CFS-like caseness and less cognitive difficulties. Lower physical functioning scores were predictive of (the development of) CFS-like caseness. CONCLUSION: Recovering from persistent fatigue and work resumption seem to result from different underlying processes and do not necessarily fall together. As many factors associated with outcome in fatigue reflect illness perception, the prevention of persistent fatigue and CFS may partly be achieved by the modification of perception.     

Childhood experiences of illness and parenting in adults with chronic fatigue syndrome

OBJECTIVE: There are many similarities between chronic fatigue syndrome (CFS), the somatoform disorders and problems otherwise known as "medically unexplained symptoms." There is some evidence to suggest that a combination of inadequate parenting and early illness experience may predispose the individual to develop medically unexplained symptoms in adult life. The aim of this investigation was to compare the contributions of childhood experiences of illness and parenting in adults with CFS with a fracture clinic control group. METHOD: A retrospective case control design was used. Thirty patients with a diagnosis of CFS and 30 patients attending a fracture clinic in an inner London teaching hospital completed questionnaires measuring parental care and protection and were interviewed about childhood experiences of illness. RESULTS: There were no differences in childhood experience of illness in the two groups. However, logistic regression revealed that maternal overprotection and depression were associated with the diagnosis of CFS. CONCLUSION: The findings may represent risk factors for the development of CFS in adult life. It is possible that maternal overprotection in particular is related to the formation of belief systems about avoiding activity that operate to adversely influence behaviour in patients with CFS.