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.     

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.     

Undiagnosed and comorbid disorders in patients with presumed chronic fatigue syndrome

Objective

To assess undiagnosed and comorbid disorders in patients referred to a tertiary care center with a presumed diagnosis of chronic fatigue syndrome (CFS).

Methods

Patients referred for chronic unexplained fatigue entered an integrated diagnostic pathway, including internal medicine assessment, psychodiagnostic screening, physiotherapeutic assessment and polysomnography + multiple sleep latency testing. Final diagnosis resulted from a multidisciplinary team discussion. Fukuda criteria were used for the diagnosis of CFS, DSM-IV-TR criteria for psychiatric disorders, ICSD-2 criteria for sleep disorders.

Results

Out of 377 patients referred, 279 (74.0%) were included in the study [84.9% female; mean age 38.8 years (SD 10.3)].A diagnosis of unequivocal CFS was made in 23.3%. In 21.1%, CFS was associated with a sleep disorder and/or psychiatric disorder, not invalidating the diagnosis of CFS. A predominant sleep disorder was found in 9.7%, 19.0% had a psychiatric disorder and 20.8% a combination of both. Only 2.2% was diagnosed with a classical internal disease.In the total sample, a sleep disorder was found in 49.8%, especially obstructive sleep apnea syndrome, followed by psychophysiologic insomnia and periodic limb movement disorder. A psychiatric disorder was diagnosed in 45.2%; mostly mood and anxiety disorder.

Conclusions

A multidisciplinary approach to presumed CFS yields unequivocal CFS in only a minority of patients, and reveals a broad spectrum of exclusionary or comorbid conditions within the domains of sleep medicine and psychiatry. These findings favor a systematic diagnostic approach to CFS, suitable to identify a wide range of diagnostic categories that may be subject to dedicated care.     

Physicians' diagnoses of psychiatric disorders for people with chronic fatigue syndrome

OBJECTIVE: To examine rates of psychiatric diagnoses given by patients' primary or regular physicians to persons with chronic fatigue syndrome (CFS), persons with psychiatrically explained fatigue, and a control group. Physicians' psychiatric diagnosis and participants' self-reported psychiatric diagnoses were compared to lifetime psychiatric diagnoses as measured by a structured psychiatric interview. METHOD: Participants were recruited as part of a community-based epidemiology study of chronic fatigue syndrome. Medical records of 23 persons with chronic fatigue syndrome, 25 persons with psychiatrically explained chronic fatigue, and 19 persons without chronic fatigue (controls) were examined to determine whether their physician had given a diagnosis of mood, anxiety, somatoform, or psychotic disorder. Lifetime psychiatric status was measured using the Structured Clinical Interview for the DSM-IV (SCID). Participants' self reports of specific psychiatric disorders were assessed as part of a detailed medical questionnaire. RESULTS: Physicians' diagnosis of a psychiatric illness when at least one psychiatric disorder was present ranged from 40 percent in the psychiatrically explained group, 50 percent in the control group, and 64.3 percent in the CFS group. Participants in the psychiatrically explained group were more accurate than physicians in reporting the presence of a psychiatric disorder, and in accurately reporting the presence of a mood or anxiety disorder. CONCLUSIONS: The present investigation found underrecognition of psychiatric illness by physicians, with relatively little misdiagnosis of psychiatric illness. Physicians had particular difficulty assessing psychiatric disorder in those patients whose chronic fatigue was fully explained by a psychiatric disorder. Results emphasized the importance of using participant self report as a screening for psychiatric disorder.     

Strength and physiological response to exercise in patients with chronic fatigue syndrome

OBJECTIVE: To measure strength, aerobic exercise capacity and efficiency, and functional incapacity in patients with chronic fatigue syndrome (CFS) who do not have a current psychiatric disorder. METHODS: Sixty six patients with CFS without a current psychiatric disorder, 30 healthy but sedentary controls, and 15 patients with a current major depressive disorder were recruited into the study. Exercise capacity and efficiency were assessed by monitoring peak and submaximal oxygen uptake, heart rate, blood lactate, duration of exercise, and perceived exertion during a treadmill walking test. Strength was measured using twitch interpolated voluntary isometric quadriceps contractions. Symptomatic measures included physical and mental fatigue, mood, sleep, somatic amplification, and functional incapacity. RESULTS: Compared with sedentary controls, patients with CFS were physically weaker, had a significantly reduced exercise capacity, and perceived greater effort during exercise, but were equally unfit. Compared with depressed controls, patients with CFS had significantly higher submaximal oxygen uptakes during exercise, were weaker, and perceived greater physical fatigue and incapacity. Multiple regression models suggested that exercise incapacity in CFS was related to quadriceps muscle weakness, increased cardiovascular response to exercise, and body mass index. The best model of the increased exercise capacity found after graded exercise therapy consisted of a reduction in submaximal heart rate response to exercise. CONCLUSIONS: Patients with CFS were weaker than sedentary and depressed controls and as unfit as sedentary controls. Low exercise capacity in patients with CFS was related to quadriceps muscle weakness, low physical fitness, and a high body mass ratio. Improved physical fitness after treatment was associated with increased exercise capacity. These data imply that physical deconditioning helps to maintain physical disability in CFS and that a treatment designed to reverse deconditioning helps to improve physical function.     

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.     

An overview of chronic fatigue syndrome

BACKGROUND: Psychological and immunologic factors both appear to contribute to chronic fatigue syndrome (CFS). By comparing CFS with other disorders in which fatigue is a prominent symptom, the association between fatigue, psychological vulnerability, depression, and immune function may be further defined. Recent data from psychological, neurologic, and immunologic studies that address these issues are reviewed. METHOD: Articles and abstracts covering CFS and related topics of fatigue, depression, and postinfectious syndromes were identified through MEDLINE and Index Medicus (1980-1990) and by bibliographic review of pertinent review articles. RESULTS: The 1988 definition of CFS by the Centers for Disease Control encompasses several conditions in which the major characteristic is severe fatigue associated with constitutional symptoms. Several studies have identified immune dysfunction in CFS patients, but the specificity of these findings remains unclear. Most studies have shown that CFS patients, compared with other patients with chronic medical illness, experience more disabling fatigue. Some investigators have found a higher incidence of concurrent and past psychiatric illness in CFS patients compared with other medical patients, thereby suggesting an underlying psychopathology in CFS. However, other studies have not found a higher than expected incidence of past depression in CFS patients and have further shown that many CFS patients have no identifiable psychopathology. CONCLUSION: CFS appears to be a heterogenous entity. Although there may be a high coincidence of major depression in CFS, a substantial proportion of patients lack any identifiable DSM-III-R psychiatric disorder yet still manifest the syndrome, thereby suggesting it has an autonomous entity. Despite the evolving nature of our current understanding of CFS, a rational diagnostic and therapeutic approach to CFS is possible.     

Alexithymia in adolescents with chronic fatigue syndrome

BACKGROUND: Alexithymia is postulated as an important factor in the development of medically unexplained physical symptoms. Chronic fatigue syndrome (CFS) is presently medically unexplained. The aim of this study was to investigate whether the prevalence of alexithymia was higher in adolescents with CFS compared to healthy adolescents. Comorbidity such as anxiety and depression were analyzed as possible confounding factors. Secondly, alexithymia was investigated as a prognostic factor for the recovery of CFS. METHODS: A cross-sectional study was performed among 40 adolescent outpatients diagnosed with CFS and 36 healthy controls. The 20-item Toronto Alexithymia Scale was used to assess all participants for alexithymia. Additionally, all participants completed a number of questionnaires regarding fatigue (Checklist Individual Strength), somatic complaints (Checklist Somatization Inventory), depression (Children's Depression Inventory), and trait anxiety (Spielberger State Trait Anxiety Questionnaire). A follow-up study was performed among the CFS adolescents 1 1/2 years after the initial assessment. RESULTS: CFS adolescents scored higher only on the subscale identifying feelings of the TAS-20 [mean difference after adjustment for depression and anxiety 2.8 (95% CI: 0.6; 4.9]. Twelve CFS adolescents (30%) fulfilled criteria for alexithymia. This subgroup was characterized by higher scores for depression and anxiety and equal scores for fatigue and somatic complaints. At follow-up, no differences in recovery were established between the alexithymic and nonalexithymic CFS adolescents. CONCLUSIONS: Alexithymia neither appears to be a unique correlate of CFS nor to be a prognostic factor for recovery of the CFS illness.     

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.     

Measuring disability in patients with chronic fatigue syndrome: reliability and validity of the Work and Social Adjustment Scale

Background

Disability is a defining feature of chronic conditions, and it is an increasingly used measure of therapy effectiveness. The Work and Social Adjustment Scale (WSAS) is a simple and clear measure of disability. Although the scale is widely used, no study has yet investigated its psychometric properties in patients with chronic fatigue syndrome (CFS).

Methods

Data from two samples of patients were used, one from a multicenter randomized controlled clinical trial of treatments for CFS (n =639) and the other from a clinic that specializes in CFS (n=384). All patients completed the WSAS as well as other measures.

Results

Internal consistency and the Spearman-Brown split-half coefficient values indicated that the scale is reliable. CFS patients who had comorbid diagnoses of depression, anxiety or fibromyalgia had higher WSAS scores. High levels of disability were associated with high number of physical symptoms, severe fatigue, depression, anxiety, poor sleep quality and poor physical fitness, with correlation coefficients ranging between 0.41 and 0.11. Lower scores on the WSAS were modestly associated with better physical functioning as well as higher levels of physical capacity as assessed by a walking test. Sensitivity to change was evaluated in a subgroup of patients who had undergone a course of cognitive behavioral therapy. Disability significantly decreased after therapy and remained stable at follow-ups.

Conclusion

The WSAS is a reliable and valid assessment tool for disability in patients with CFS.     

Urinary free cortisol in chronic fatigue syndrome

OBJECTIVE: The authors measured 24-hour urinary free cortisol in a group of well-characterized patients with chronic fatigue syndrome. METHOD: They obtained 24-hour urine collections from 121 consecutive clinic patients with chronic fatigue syndrome and 64 comparison subjects without the syndrome. RESULTS: Urinary free cortisol was significantly lower in the subjects with chronic fatigue syndrome regardless of the presence or absence of current or past comorbid psychiatric illness. Lower levels of urinary free cortisol were not related to medication use, sleep disturbance, or disability levels. CONCLUSIONS: There is mild hypocortisolism in chronic fatigue syndrome. Whether a primary feature or secondary to other factors, hypocortisolism may be one factor contributing to the symptoms of chronic fatigue syndrome.     

Is the chronic fatigue syndrome an exercise phobia? A case control study

OBJECTIVE: The aim of this study was to test whether patients with chronic fatigue syndrome (CFS) have an exercise phobia, by measuring anxiety-related physiological and psychological reactions to ordinary activity and exercise. METHODS: Patients and healthy but sedentary controls were assessed over 8 h of an ordinary day, and before, during and after an incremental exercise test on a motorised treadmill. To avoid confounding effects, those with a comorbid psychiatric disorder were excluded. Heart rate, galvanic skin resistance (GSR) and the amount of activity undertaken were measured, along with state and trait measures of anxiety. RESULTS: Patients with CFS were more fatigued and sleep disturbed than were the controls and noted greater effort during the exercise test. No statistically significant differences were found in either heart rate or GSR both during a normal day and before, during and after the exercise test. Patients with CFS were more symptomatically anxious at all times, but this did not increase with exercise. CONCLUSION: The data suggest that CFS patients without a comorbid psychiatric disorder do not have an exercise phobia.     

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.     

Seasonal affective disorder presenting as chronic fatigue syndrome.

Although operational criteria have been recently proposed to better define chronic fatigue syndrome (CFS), it remains a controversial diagnosis. There are many overlapping symptoms between CFS and major depression. The author presents two patients with seasonal affective disorder, who responded to phototherapy and had previously been diagnosed as CFS. Because of the consequences of treatment, seasonal and non seasonal depression need to be ruled out in patients with chronic fatigue symptoms.     

Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents

In the adolescent population, fatigue is associated with somatic complaints, unrefreshing sleep, cognitive disturbances and symptoms of depression and anxiety. This pattern of symptoms resembles the one described in chronic fatigue syndrome (CFS). Since immunological alterations have been reported in CFS patients, we wondered whether also severely fatigued girls from a healthy population would show comparable alterations in psychological and immunological parameters. We tested this hypothesis in a longitudinal design, allowing a reliable assessment of the participants' characteristic immune status. Groups of severely fatigued (N=67) and non-fatigued (N=61) participants were selected. Severely fatigued girls reported more depressive symptoms, anxiety, reduced sleep quality, and somatic and CFS-related symptoms than non-fatigued participants across three measurements during one year (T1: spring, T2: autumn, T3: spring). In contrast, no group differences in mitogen-induced cytokine production or T-cell proliferation in vitro or in leukocyte subset counts were observed. Although absolute cytokine production and cell counts were affected by seasonal variation, the within-subject values, relatively to the rest of the participants, were fairly stable. Data from a small group of CFS patients (N=11) showed similarities in self-reported complaints between CFS patients and fatigued participants. Interestingly, CFS patients showed a distinct immune profile when compared to the severely fatigued or non-fatigued participants, i.e. increased levels of anti-inflammatory cytokines (IL-10, decreased IFN-gamma/IL-10 ratio) and reduced levels of pro-inflammatory cytokines (IL-6, TNF-alpha) over all three time points analyzed. These results show that, although overlap in symptomatology between the general population and patients with CFS was observed, only CFS patients show a skewing of the cytokine balance towards an anti-inflammatory profile.     

Nefazodone for patients with chronic fatigue syndrome.

OBJECTIVE: Patients with chronic fatigue syndrome (CFS) present with a variety of musculoskeletal, neurocognitive, sleep disturbance and mood symptoms. An open evaluation of the clinical utility of the novel antidepressant compound, nefazodone, was completed. METHOD: Ten patients with CFS presenting for assessment by a specialist psychiatrist were treated with nefazodone. Patients treated within this specialist service are also advised to engage in appropriate behavioural and sleep-wake cycle strategies to improve their level of functioning. RESULTS: Of the 10 patients, eight (80%) reported at least some improvement in the key symptom of fatigue, with four (40%) reporting moderate or marked symptom relief. Additionally, sleep disturbance and mood were both moderately or markedly improved in seven (70%) and eight (80%) of the patients, respectively. Five of the patients (50%) achieved at least a moderate improvement in overall functional outcome and were able to return to work or their previous level of role function. The mean dose of nefazodone was 370 mg/day (range = 200-800 mg), with a strong preference for nocturnal dosing. Seven of the patients had previously failed to respond to moclobemide, while seven had previously failed to respond to conventional antidepressant therapy. CONCLUSION: Nefazodone appears to be worthy of further systematic investigation in patients with CFS. Given its effects on sleep, mood and anxiety symptoms, it may have particular advantages in patients with this disorder.     

Autonomic function and serum erythropoietin levels in chronic fatigue syndrome

OBJECTIVE: Given previous findings, we wished to investigate whether there was evidence of autonomic dysfunction in patients with chronic fatigue syndrome, and whether this could be related to reduced erythropoietin levels and altered red blood cell indices. METHODS: We assessed autonomic function and analysed blood parameters (including erythropoietin) in 22 patients with chronic fatigue syndrome who were medication-free and without comorbid depression or anxiety. Results were compared to 23 iron-deficiency anaemia patients and 18 healthy individuals. RESULTS: Autonomic testing in patients with chronic fatigue syndrome yielded a significantly greater increase in heart rate together with a more pronounced systolic blood pressure fall on standing compared to healthy individuals. Heart rate beat-to-beat variation on deep breathing and responses to the Valsalva manoeuvre were normal. Two of 22 patients with chronic fatigue had mild normochromic normocytic anaemia with normal ferritin, vitamin B12 and folate levels. Serum erythropoietin levels were within reference range. CONCLUSION: Some autonomic dysfunction is present in chronic fatigue syndrome (CFS) patients; the explanation remains uncertain, but could relate to cardiovascular deconditioning. There were no major haematological, biochemical or immunological abnormalities in these patients.     

Illness perceptions and levels of disability in patients with chronic fatigue syndrome and rheumatoid arthritis

OBJECTIVE: To investigate the strength of chronic fatigue syndrome (CFS) patients' negative illness perceptions by comparing illness perceptions and self-reported disability in patients with CFS and rheumatoid arthritis (RA). METHODS: Seventy-four RA patients and 49 CFS patients completed the Illness Perception Questionnaire-Revised and the 36-item Short-Form Health Survey. RESULTS: When compared to the RA group, the CFS group attributed a wider range of everyday somatic symptoms to their illness, perceived the consequences of their illness to be more profound and were more likely to attribute their illness to a virus or immune system dysfunction. Both groups reported equivalent levels of physical disability but the CFS group reported significantly higher levels of role and social disability. CONCLUSION: Although the symptoms of CFS are largely medically unexplained, CFS patients have more negative views about their symptoms and the impact that these have had on their lives than do patients with a clearly defined and potentially disabling medical condition. The data support the cognitive behavioural models of CFS that emphasise the importance of patients' illness perceptions in perpetuating this disorder.     

Stressors, personality traits, and coping of Gulf War veterans with chronic fatigue

Objectives: preliminary surveys of Persian Gulf veterans revealed a significant prevalence of self-reported symptoms consistent with chronic fatigue syndrome (CFS). The purpose of this study was to compare self-reported life stressors, combat, and chemical exposures, personality and coping between Gulf War veterans with CFS and healthy veterans.Methods: following a complete physical, psychiatric, and neuropsychological evaluation, 45 healthy veterans, 35 veterans with CFS and co-morbid psychiatric disorder, and 23 veterans with CFS and no co-morbid psychiatric disorder completed questionnaires assessing war and non-war-related life stressors, self-reports of environmental exposure (e.g. oil well fires, pesticides), personality, and coping.Results: measures of personality, self-reported combat and chemical exposures, and negative coping strategies significantly differentiated healthy veterans from those with CFS.Conclusion: a biopsychosocial model of veterans' illness was supported by the fact that personality, negative coping strategies, life stress after the war, and environmental exposures during the war were significant predictors of veterans' current physical function.     

Psychiatric morbidity and illness experience of primary care patients with chronic fatigue in Hong Kong

OBJECTIVE: The authors' goal was to examine the prevalence and experience of psychiatric morbidity among primary care patients with chronic fatigue in Hong Kong. METHOD: One hundred adult patients with medically unexplained fatigue for 6 or more months were assessed with the Explanatory Model Interview Catalogue, psychopathological rating scales, and an enhanced version of the Structured Clinical Interview for DSM-III-R. RESULTS: The lifetime prevalence of DSM-III-R depressive and anxiety disorders was 54%. Current depressive and anxiety disorders were identified in 28 patients, who exhibited more psychopathology and functional impairment than other patients. Thirty-three patients had somatoform pain disorder, and 30 had undifferentiated somatoform disorder, but most of them could also be diagnosed as having shenjing shuairuo (weakness of nerves) and, to a lesser extent, ICD-10 neurasthenia. Chronic fatigue syndrome diagnosed according to the 1988 Centers for Disease Control criteria was rare (3%) and atypical. Generally, patients mentioned fatigue if asked, but pains (36%), insomnia (20%), and worries (13%) were the most troublesome symptoms. Most patients attributed illness onset to psychosocial sources. CONCLUSIONS: Psychiatric morbidity was common among primary care patients with chronic fatigue. Subthreshold psychiatric morbidity was very common and was more validly represented by the disease construct of shenjing shuairuo or neurasthenia than somatoform disorder.