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Chronic fatigue and chronic fatigue syndrome: shifting boundaries and attributions.

The subjective symptom of "fatigue" is one of the most widespread in the general population and is a major source of healthcare utilization. Prolonged fatigue is often associated with neuropsychological and musculoskeletal symptoms that form the basis of several syndromal diagnoses including chronic fatigue syndrome, fibromyalgia, and neurasthenia, and is clearly not simply the result of a lack of force generation from the muscle. Current epidemiologic research in this area relies predominantly on self-report data to document the prevalence and associations of chronic fatigue. Of necessity, this subjective data source gives rise to uncertain diagnostic boundaries and consequent divergent epidemiologic, clinical, and pathophysiologic research findings. This review will highlight the impact of the case definition and ascertainment methods on the varying prevalence estimates of chronic fatigue syndrome and patterns of reported psychological comorbidty. It will also evaluate the evidence for a true postinfective fatigue syndrome.

Chronic Disease↗

Effect of three triterpenoid compounds isolated from root bark of Aralia elata on stimulus-induced superoxide generation and tyrosyl phosphorylation and translocation of p47(phox) and p67(phox) to cell membrane in human neutrophil.

BACKGROUND: Root bark of Aralia elata is used as a folk medicine for neurasthenia, rheumatism, diabetes, hepatitis virus and spasm of the stomach in China, Japan and Russia. METHODS: The effect of three triterpenoid compounds isolated from root bark of A. elata on stimulus-induced superoxide generation and tyrosyl phosphorylation and translocation of p47(phox) and p67(phox) to cell membrane was investigated. The three compounds examined were Elatoside A, Elatoside C, and Tarasaponin V. RESULTS: When the cells were preincubated with these compounds, the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was suppressed in a low concentration range. However, the superoxide generation was significantly enhanced by 40 micromol/l triterpenoid, and was again suppressed in the higher concentration range. In the case of superoxide generation induced by phorbol 12-myristate 13-acetate (PMA), the compounds had no obvious effect on the superoxide generation in low concentration but suppressed that at 40 micromol/l. These compounds also efficiently suppressed the superoxide generation induced by arachidonic acid (AA) at 10 micromol/l. In parallel to the effect on the fMLP-induced superoxide generation, these compounds suppressed fMLP-induced tyrosyl phosphorylation and the translocation to membrane of cytosolic compounds, p47(phox) and p67(phox) at 10 and 80 micromol/l but not at 40 micromol/l. CONCLUSIONS: Triterpenoid saponins examined in this study effect stimulus-induced superoxide generation and tyrosyl phosphorylation and translocation to membrane of p47(phox) and p67(phox) in a concentration-dependent manner, and may have some pharmaceutical applications.

Arachidonic Acid↗

The prevalence of somatoform disorders among internal medical inpatients.

OBJECTIVE: To find the prevalence of somatoform disorders (SDs) among internal medical inpatients and to study the comorbidity with other psychiatric disorders. METHODS: Of 392 eligible consecutive medical inpatients, 294 (75%) accepted to participate and, using a two-phase design, were assessed for ICD and DSM-IV somatoform diagnoses and for ICD-10 psychiatric diagnoses. RESULTS: A total of 18.1% (95% CI: 12.8-24.9%) of the patients fulfilled the diagnostic criteria for an ICD-10 disorder, and 20.2% (95% CI:14.7-27.2% ) for a DSM-IV SD. The prevalence of specified disorders revealed marked differences between the two diagnostic systems, e.g., concerning somatisation disorder (SD), which was more prevalent in the ICD-10 (5%) than in the DSM-IV (1.5%) equivalent. Quite the contrary was found in undifferentiated SD (0.7% in ICD-10 and 10% in DSM-IV). According to ICD-10 criteria, 3.5% had hypochondriasis, 2.6% a dissociative disorder, 3.2% a somatoform autonomic dysfunction, 1.5% had neurasthenia or persistent somatoform pain disorder, and 5% had an SD, unspecified. SDs were more prevalent among younger females. Thirty-six percent of the patients with SDs also had another psychiatric disorder, 11% a depression, and 25% an anxiety disorder. The physicians detected about 1/3 of the cases. CONCLUSION: Somatoform disorders were prevalent among internal medical inpatients especially among younger women.

Adult↗

Toward validation of atypical depression in the community: results of the Zurich cohort study.

AIMS: This paper (1) examines the validity of the atypical subtype of depression in a community-based longitudinal cohort study, (2) presents estimates of the prevalence and sex differences of DSM-IV atypical depression and a newly more broadly defined atypical syndrome in the community and (3) compares the clinical correlates and treatment patterns of those with atypical depression with other depressives. METHODS: The Zurich cohort study is comprised of 591 subjects selected from a population-based cohort of young adults representative of the canton of Zurich in Switzerland, who were screened in 1978 with the Symptom Checklist 90-R [L.R. Derogatis (1977)] and followed prospectively with five interviews between 1979 and 1993. Atypical depression was defined on a spectrum ranging from atypical major to minor to atypical depressive symptoms alone. RESULTS: The rate of DSM-IV atypical major depressive episodes in this community is 4.8% and for major atypical depression syndrome is 7.3%. Whereas there was no marked sex difference for nonatypical features, there was a significant female preponderance for DSM-IV and broadly defined atypical depressive subtypes. Systematic investigation of the diagnostic criteria for atypical depression revealed that a nonhierarchical definition of atypical depression with respect to mood reactivity yielded as valid a syndromic definition as the current hierarchy based on mood reactivity as an essential feature. Very high comorbidity (odd ratios>2.0) was found with seasonality, bipolar II, social phobia, binge eating, neurasthenia and sociopathy. LIMITATIONS: Atypical depression was not defined à priori, its criteria were derived from two sections of the Zurich interview. CONCLUSIONS: Atypical depression has high population prevalence and substantial significance in terms of clinical severity, impairment, and service use. The intriguing finding that the sex difference in depression may be attributed to atypical features of depression will need further investigation. Overall, our data indicate that the atypical subtype of depression is a valid entity based on evidence from such traditional indicators of validity as inclusion criteria and indicators of course. However, there are some problems with discriminatory validity from other disorders. Although comorbidity with these disorders may in part reflect an operational artifact of symptom overlap, further work needs to be done in distinguishing atypical depression from bipolar II.

Adult↗

[Chronic fatigue syndrome: a critical review].

The term "chronic fatigue syndrome" (CFS) applies to a condition of unknown aetiology characterized clinically by an association of subjective symptoms, the most constant being an invalidating tiredness. The diagnostic criteria in current use do not permit to isolate an homogeneous subgroup among patients consulting for chronic asthenia. In the present state of research no infectious or immunological cause has been demonstrated conclusively, although a persistent enterovirus or herpesvirus type 6 infection or a state of chronic immune activation seem to play a role in some cases. Patients who fulfill the criteria of CFS present with psychiatric overmorbidity, essentially depressive, and in 50% of the cases with the mental disorders preceding CFS. The various theoretical models linking CFS to psychopathology are discussed, and finally the syndrome is regarded as a social construction reproducing or renovating the neurasthenia of the late 19th century. There is no specific treatment of CFS, but antidepressants, cognitive-behavioural therapy and perhaps certain immuno-modulators can be useful. The future lines of research should endeavour to isolate a subgroup of patients with prolonged asthenia after a recognized episode of infection and to identify the immunological, psychological and behavioral characteristics of this particular group as well as their reciprocal interactions.

Adult↗

Tumour necrosis factor-alpha is increased in the cerebrospinal fluid and serum of ischaemic stroke patients and correlates with the volume of evolving brain infarct.

A growing body of evidence suggests the involvement of inflammatory mediators, including cytokines, in the development of ischaemic brain lesions. The aim of the present study was to investigate whether tumour necrosis factor-alpha (TNF-alpha), the proinflammatory cytokine, contributes to early pathophysiological mechanisms leading to brain damage as a consequence of acute stroke. We have studied TNF-alpha levels in cerebrospinal fluid (CSF) and serum in 23 stroke patients within the first 24 hours after ischaemic stroke, confirmed by computerized tomography of the brain (CT). The control group consisted of 15 patients with the diagnosis of tension headache and neurasthenia. In stroke patients the levels of TNF-alpha both in CSF and serum were significantly higher in comparison with the control group. The positive correlation between the levels of TNF-alpha in CSF and serum of the studied patients has been observed. Furthermore, a positive correlation between both TNF-alpha levels in CSF and serum and the volume of evolving brain infarct have been shown.

Adult↗

Prognosis of adult men with heat exhaustion with regard to postural stability and neurobehavioral effects: a 6-month follow-up study.

The medical complications of heat disorders, including hematological, cardiovascular and renal damage, have been well documented. However, very little has been written on its neurological complications. In an earlier study, we reported that men with heat exhaustion, studied 2 weeks after the acute episode, had significantly more symptoms of neurasthenia, poorer performance in short-term memory and slower reaction time. The cases (as a group) had significantly poorer postural stability. The objective of this study was to assess the prognosis of men with heat exhaustion with regard to postural stability and neurobehavioral functions 12, 3 and 6 months after the acute episode. The study is prospective in design and spans a 2-year period. All soldiers who were diagnosed to have heat exhaustion (cases) from 1 March 1998 were included in the study. For each case, a healthy soldier (matched for age, ethnicity, years of education and military vocation) was recruited to serve as control. Each subject had a neurobehavioral assessment by using the Swedish Performance Evaluation System (SPES), a computerized test battery. The postural stability of the subjects was assessed using a computerized postural sway system. Each subject took the test 2 weeks after the acute episode and repeated the test 3 and 6 months later for duration of 2 years. We report here the findings of 21 heat exhaustion cases and 18 controls, which completed all the three tests (i.e. done 2 weeks after the acute episode and 3 and 6 months later). Significant differences were only detected in some of the neurobehavioral and neurophysiological parameters between the cases and the control for first two tests but not the third test. The prognosis of adult with heat exhaustion is good. There were no significant differences in neurobehavioral tests and postural stability among the cases and controls 612 months after the episode.

Adolescent↗

Genotoxicity and chronic health effects of automobile exhaust: a study on the traffic policemen in the city of Lanzhou.

A study on the health and genotoxic effects of occupational exposure to automobile exhaust was carried out among traffic policemen in Lanzhou (China) in 1996. A total of 78 traffic policemen working in the field was the exposed group, and 57 household register policemen working in the office was the control group. The health effects were evaluated by health questionnaires. Significant differences were observed between the exposed and control groups with respect to the morbidity of rhinitis, pharyngitis, trachoma, syndrome of neurasthenia and joint pain, apart from disorders in the digestive system. The percentage of rhinitis and pharyngitis obtained in the two groups was significantly higher among the smokers than among the nonsmokers. The frequencies of micronuclei (MN) and sister-chromatid exchanges (SCEs) were measured in peripheral blood lymphocytes from the two groups of volunteers. Compared with the control group, statistically significant increases of MN and SCE were found for the exposed group. The increase in the induction of MN and SCE among the traffic policemen and household register policemen is enhanced further by smoking.

Adult↗

Psychiatric symptoms, personality and ways of coping in chronic fatigue syndrome.

This study aimed to investigate the psychological characteristics of chronic fatigue syndrome (CFS: Holmes et al. 1988). A battery of psychometric instruments comprising the General Health Questionnaire (GHQ), the Beck Depression Inventory (BDI), the Minnesota Multiphasic Personality Inventory (MMPI) and the Lazarus Ways of Coping (WoC) inventory, was administered to a sample of clinically-defined CFS sufferers (N = 58), to a comparison group of chronic pain (CP) patients (N = 81) and to a group of healthy controls matched for sex and age with the CFS sample (N = 104). Considerable overlap was found between CFS and CP patients at the level of both physical and psychological symptoms. This raises the possibility that CFS sufferers are a sub-population of CP patients. However, while there was some commonality between CFS and CP patients in terms of personality traits, particularly the MMPI 'neurotic triad' (hypochondriasis, depression and hysteria), CFS patients showed more deviant personality traits reflecting raised levels on the first MMPI factor, emotionality. Moreover, results were not consistent with the raised emotionality being a reaction to the illness, but rather were consistent with the hypothesis that emotionality is a predisposing factor for CFS. The majority of CFS patients fell within four personality types, each characterized by the two highest MMPI scale scores. One type (N = 20) reported a lack of psychological symptoms or emotional disturbance contrary to the overall trend for the CFS sample. This group conformed to the ICD-10 classification of neurasthenia.

Adaptation, Psychological↗

Symptomatology of minor psychiatric morbidity: a crosscultural comparison.

The basic symptoms of minor psychiatric morbidity (MPM) reported elsewhere were also found in a community survey in Taiwan. However, differences in the patterns of and manifestations of the symptoms were evident. Contrary to most Western surveys, the prevalence of anxiety (24.7%) was found to be higher than that of depression (8.3%) in Taiwan. Possible explanations based on sociocultural characteristics of the Chinese family were proposed. The notion of somatization as a predominant symptom in Chinese neurotic patients advocated by some research workers was not supported in this study. As a result of findings in community cases, it is argued that the importance of somatization has been considerably overemphasized as a factor in the illness behaviour of neurotic cases in Chinese and other cultures, and it is therefore not a culture-specific disease phenomenon. It is also suggested that certain culture-specific neurotic syndromes reported in Chinese, such as shen-ching-shuai-jo (neurasthenia) and shen-k'uei (semen loss syndrome), are clinically equivalent to MPM. Implications of the present findings on crosscultural research and management of MPM were discussed.

Adolescent↗

Chronic fatigue in primary care attenders.

From 686 patients attending primary care physicians, 77 were identified by a screening procedure as having chronic fatigue. Of these, 65 were given a comprehensive psychological, social and physical evaluation. Seventeen cases (26%) met criteria for the chronic fatigue syndrome. Forty-seven (72%) received an ICD-9 diagnosis of whom 23 had neurotic depression, with a further 5 meeting criteria for neurasthenia. Forty-nine were 'cases' as defined by the revised Clinical Interview Schedule (CIS-R), and 42 if the fatigue item was excluded. Psychiatric morbidity was more related to levels of social stresses than was severity of fatigue. The main difference between these subjects and those examined in hospital settings is that the former are less liable to attribute their symptoms to wholly physical causes, including viruses, as opposed to social or psychological factors. Identification and management of persistent fatigue in primary care may prevent the secondary disabilities seen in patients with chronic fatigue syndromes.

Adult↗

Diagnostic disclosure: a tale in two cultures.

Diagnostic communication between doctors and patients is thought to differ radically between Japan and Western countries. To understand diagnostic disclosure to psychiatric patients, a questionnaire with six case vignettes was sent to practising psychiatrists in Japan (N = 166) and North America (N = 112). While over 90% of both groups would inform patients with affective and anxiety disorders of their diagnoses, only 70% of North Americans and less than 30% of Japanese would similarly inform patients with schizophrenia or schizophreniform disorders. The Japanese preferred alternative was to give a vague alternative diagnosis such as neurasthenia. North Americans would discuss differential diagnoses with the patient instead. Nearly all in both groups would inform the family, but North Americans would do so only with patient consent. For disorders for which there are effective treatments, diagnostic disclosure is common to both cultures; when prognosis is uncertain or the diagnosis is feared, as in schizophrenia, culturally constructed views of patienthood govern disclosure practice.

Adult↗

One-year outcome of unexplained fatigue syndromes in primary care: results from an international study.

BACKGROUND: Outcome studies of chronic fatigue, neurasthenia and other unexplained fatigue syndromes are few and have been carried out in developed Western countries. This paper aimed to study the outcome of unexplained fatigue syndromes in an international primary care sample and to identify risk factors for persistence. METHOD: We used data from the WHO collaborative study of psychological problems in general health care, in which 3201 primary care attenders from 14 countries were followed-up for 12 months. The assessment included a modified version of the Composite International Diagnostic Interview. RESULTS: Unexplained fatigue persisted in one-fifth to one-third of the subjects depending on the definition of fatigue. From the factors studied only severity of fatigue and psychiatric morbidity at baseline were associated with persistence 12 months later. Outcome did not differ between countries of different stages of economic development. CONCLUSIONS: The prognosis of fatigue syndromes in international primary care is relatively good. The study underlines the importance of psychological factors in influencing short-term prognosis.

Fatigue Syndrome, Chronic↗

The structure of common DSM-IV and ICD-10 mental disorders in the Australian general population.

BACKGROUND: Patterns of co-occurrence among the common mental disorders may provide information about underlying dimensions of psychopathology. The aim of the current study was to determine which of four models best fits the pattern of co-occurrence between 10 common DSM-IV and 11 common ICD-10 mental disorders. METHOD: Data were from the Australian National Survey of Mental Health and Well-Being (NSMHWB), a large-scale community epidemiological survey of mental disorders. Participants consisted of a random population-based sample of 10641 community volunteers, representing a response rate of 78%. DSM-IV and ICD-10 mental disorder diagnoses were obtained using the Composite International Diagnostic Interview (CIDI), version 2.0. Confirmatory factor analysis (CFA) was used to assess the relative fit of competing models. RESULTS: A hierarchical three-factor variation of a two-factor model demonstrated the best fit to the correlations among the mental disorders. This model included a distress factor with high loadings on major depression, dysthymia, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD) and neurasthenia (ICD-10 only); a fear factor with high loadings on social phobia, panic disorder, agoraphobia and obsessive-compulsive disorder (OCD); and an externalizing factor with high loadings on alcohol and drug dependence. The distress and fear factors were best conceptualized as subfactors of a higher order internalizing factor. CONCLUSIONS: A greater focus on underlying dimensions of distress, fear and externalization is warranted.

Australia↗

A population-based incidence study of chronic fatigue.

BACKGROUND: Most research on syndromes of chronic fatigue has been conducted in clinical settings and is therefore subject to selection biases. We report a population-based incidence study of chronic fatigue (CF) and chronic fatigue syndrome (CFS). METHODS: Questionnaires assessing fatigue and emotional morbidity were sent to 695 adult men and women who had replied to a postal questionnaire survey 1 year earlier. Possible CFS cases, subjects with probable psychiatric disorder and normal controls were interviewed. RESULTS: Baseline fatigue score, the level of emotional morbidity and a physical attribution for fatigue were risk factors for developing CF. However, after adjusting for confounding, premorbid fatigue score was the only significant predictor. A minority of CF subjects, all female, had consulted their general practitioner; higher levels of both fatigue and emotional morbidity were associated with consultation. Possible CFS cases reported similar rates of current and past psychiatric disorder to psychiatric controls, but after controlling for fatigue or a diagnosis of neurasthenia the current rates were more similar to those of normal controls. Two new cases of CFS were confirmed. CONCLUSIONS: Both fatigue and emotional morbidity are integral components of chronic fatigue syndromes. The demographic and psychiatric associations of CFS in clinical studies are at least partly determined by selection biases. Given that triggering and perpetuating factors may differ in CFS, studies that examine the similarities and differences between chronic fatigue syndromes and psychiatric disorder should consider both the stage of the illness and the research setting.

Adult↗

Extraintestinal symptoms in irritable bowel syndrome and inflammatory bowel diseases: nature, severity, and relationship to gastrointestinal symptoms.

Patients suffering from the irritable bowel syndrome (IBS) tend to have extraintestinal symptoms. The purposes of this study were to compare the nature and severity of these symptoms in IBS patients in relation to patients with inflammatory bowel disease (IBD) and to nonpatients and to clarify the relationship between intestinal and extraintestinal symptoms. A consecutive group of male patients and a control group of age-matched male subjects were studied. Symptoms were graded for severity using a validated, self-administered inventory. There were 53 IBS patients, 55 IBD patients (32 Crohn's disease), and 56 controls. IBS patients scored significantly higher than IBD patients on constipation, dyspepsia, and reflux scales. Musculoskeletal symptoms, neurasthenia, and sleep scores were similar in IBS and IBD patients, and both groups scored significantly higher than the controls. The scores of urinary, thoracic, and oral symptoms were similar in IBD patients and in controls. However, IBS patients scored significantly higher than both groups on all these scales. Reflux symptoms were the most powerful predictors of extraintestinal symptoms, both in IBS and in IBD. Diarrhea was predictive of extraintestinal symptoms only in IBD. In conclusion, IBS patients experienced extraintestinal symptoms to the same extent, or even more than patients with IBD. However, the relationship between intestinal and extraintestinal symptoms differed in the two conditions.

Adult↗

IL-18 in patients with multiple sclerosis.

IL-18 is a cytokine which plays an important role in Th-1 response through its ability to induce IFN-gamma production in T cells and NK cells. The purpose of the study was to measure IL-18 levels in serum and CSF of 21 patients with the relapsing-remitting form of MS, 9 with active gadolinium enhancing lesions in MRI and 12 without enhancing lesions, and to compare results with control group consisting of 11 patients with diagnosis of neurasthenia and tension headache. IL-18 concentration in the CSF and sera was measured by ELISA. We found a highly significant increase of both IL-18 CSF and serum levels in MS patients in comparison with the control group. In patients with active MRI lesions the levels of IL-18 in CSF and serum were significantly higher in comparison with the levels found in patients without enhancing lesions. The results suggest involvement of IL-18 in immunopathogenesis of MS especially in the active stages of the disease.

Adult↗

Referrals to a liaison psychiatry out-patient clinic in a UK general hospital: a report on 900 cases.

OBJECTIVE: To describe the demographic and clinical characteristics of consecutive referrals to an out-patient liaison psychiatry clinic in a large university hospital in the UK. METHOD: We studied 900 patients using a standardized proforma. Assessments of functional capacity were made using the Global Assessment of Functioning (GAF) scale, and each patient was assigned a psychiatric diagnosis using ICD-10 criteria. RESULTS: Four of five of all referrals presented with somatic complaints, and 41% had a concurrent physical illness. The most common psychiatric diagnoses were somatoform disorders (55%) and neurasthenia (11%). Although more than half (59%) had no previous psychiatric history, a surprisingly high number (35%) had significant functional impairment (scores of < 50 on the GAF scale). The lack of adequate psychological treatment services often provided a barrier to optimal management of some of the more disabled patients. CONCLUSION: The general hospital liaison psychiatry clinic provides an acceptable setting in which to assess and manage patients referred from non-psychiatric colleagues.

Adult↗