Search

Context: Unexplained fatigue states are prevalent, with uncertain diagnostic boundaries., Objective: Patients with fatigue-related illnesses were investigated by questionnaire and a novel semistructured interview to identify discriminatory features., Methods: Cross-sectional samples of women from specialist practices with chronic fatigue syndrome (n = 20), postcancer fatigue (PCF; n = 20), or major depression (n = 16) were recruited. Additionally, two longitudinal samples were studied: women with fatigue associated with acute infection who subsequently developed postinfective fatigue syndrome (n = 20) or recovered uneventfully (n = 21), and women undergoing adjuvant therapy for breast cancer experiencing treatment-related fatigue who subsequently developed PCF (n = 16) or recovered uneventfully (n = 16). Patients completed self-report questionnaires, and trained interviewers applied the Semi-structured Clinical Interview for Neurasthenia. The receiver operating characteristics curves of the interview were measured against clinician-designated diagnoses. Cluster analyses were performed to empirically partition participants by symptom characteristics., Results: The interview had good internal consistency (Cronbach alpha "fatigue" = .83), and diagnostic sensitivity and specificity for chronic fatigue syndrome (100% and 83%) and major depression (100% and 72%), with reasonable parameters for PCF (72% and 58%). Empirical clustering by "fatigue" or "neurocognitive difficulties" items allocated most patients to one group, whereas "mood disturbance" items correctly classified patients with depression only., Conclusions: The Semi-structured Clinical Interview for Neurasthenia offers reliable diagnostic use in assessing fatigue-related conditions. The symptom domains of fatigue and neurocognitive difficulties are shared across medical and psychiatric boundaries, whereas symptoms of depression such as anhedonia are distinguishing.

Objective: To assess the efficacy of brief fatigue self-management (FSM) for medically unexplained chronic fatigue (UCF) and chronic fatigue syndrome (CFS) in primary care., Methods: A randomized controlled design was used wherein 111 patients with UCF or CFS were randomly assigned to two sessions of FSM, two sessions of symptom monitoring support (attention control; AC), or a usual care control condition (UC). Participants were assessed at baseline and at 3 and 12 months after treatment. The primary outcome, the Fatigue Severity Scale, measured fatigue impact on functioning. Analysis was by intention to treat (multiple imputation) and also by per protocol., Results: A group × time interaction across the 15-month trial showed significantly greater reductions in fatigue impact in the FSM group in comparison with the AC group (p < .023) and the UC group (p < .013). Medium effect sizes for reduced fatigue impact in the FSM group were found in comparison with the AC group (d = 0.46) and the UC group (d = 0.40). The per-protocol analysis revealed large effect sizes for the same comparisons. Clinically significant decreases in fatigue impact were found for 53% of participants in the FSM condition, 14% in the AC condition, and 17% in the UC condition. Dropout rates at the 12-month follow-up were high (42%-53%), perhaps attributable to the burden of monthly telephone calls to assess health care use., Conclusion: A brief self-management intervention for patients with UCF or CFS seemed to be clinically effective for reducing the impact of fatigue on functioning. Trial Registration clinicaltrials.gov Identifier: NCT00997451.

Objective: Functional somatic syndromes have no laboratory or pathologic abnormalities and so are diagnosed by symptom-based case definitions. However, many studies, including recent ones, have used self-reports of physician diagnosis rather than the case definitions. Our objective was to determine the sensitivities and specificities of self-report of physician diagnosis for chronic fatigue syndrome (CFS), fibromyalgia (FM), irritable bowel syndrome (IBS), panic disorder, and migraine., Methods: Each of 312 female patients with incident interstitial cystitis/bladder pain syndrome and matched population-based controls were queried on self-report of physician diagnosis and separately on established case definitions for each of these syndromes., Results: Using the symptom-based case definitions as standards, we found that self-report of physician diagnosis did not identify 90% of the controls who had CFS, 77% who had FM, 69% who had IBS, 43% who had panic disorder, and 23% who had migraine. In addition, it missed most individuals with multiple syndromes. Findings in one cohort (controls) were confirmed in another (patients with interstitial cystitis/bladder pain syndrome)., Conclusions: Self-report of physician diagnosis did not identify most of the three most venerable functional somatic syndromes, IBS, FM, and, especially, CFS; nor did it identify substantial minorities of individuals with panic disorder and migraine. Self-report of physician diagnosis was particularly poor in recognizing persons with multiple syndromes. The insensitivity of this diagnostic test has effects on not only prevalence and incidence estimates but also correlates, comorbidities, and case recruitment. To reveal individuals with these syndromes, singly or together, queries of symptoms, not diagnoses, are necessary.

Objective: To compare the prevalence of psychiatric disorders in persons with chronic fatigue syndrome (CFS) identified from the general population and a chronically ill group of people presenting with subsyndromic CFS-like illness ("insufficient symptoms or fatigue" (ISF)). Previous studies in CFS patients from primary and tertiary care clinics have found high rates of psychiatric disturbance, but this may reflect referral bias rather than true patterns of comorbidity with CFS., Methods: We used random digit dialing to identify unwell individuals. A detailed telephone interview identified those with CFS-like illness. These individuals participated in a 1-day clinical evaluation to confirm CFS or ISF status. We identified 113 cases of CFS and 264 persons with ISF. To identify current and lifetime psychiatric disorders, participants completed the Structured Clinical Interview for DSM-IV., Results: Sixty-four persons (57%) with CFS had at least one current psychiatric diagnosis, in contrast to 118 persons (45%) with ISF. One hundred one persons (89%) with CFS had at least one lifetime psychiatric diagnosis compared with 208 persons (79%) with ISF. Of note, only 11 persons (9.8%) with CFS and 25 persons (9.5%) with ISF reported having seen a mental healthcare specialist during the past 6 months., Conclusions: Our findings indicate that current and lifetime psychiatric disorders commonly accompany CFS in the general population. Most CFS cases with comorbid psychiatric conditions had not sought appropriate help during the past 6 months. These results demonstrate an urgent need to address psychiatric disorders in the clinical care of CFS cases.

Objective: To examine the neuropsychological function characterized in subjects with chronic fatigue syndrome (CFS) at the same time controlling for relevant confounding factors. CFS is associated with symptoms of neuropsychological dysfunction. Objective measures of neuropsychological performance have yielded inconsistent results possibly due to sample selection bias, diagnostic heterogeneity, comorbid psychiatric disorders, and medication usage., Method: CFS subjects (n = 58) and well controls (n = 104) from a population-based sample were evaluated, using standardized symptom severity criteria. Subjects who had major psychiatric disorders or took medications known to influence cognition were excluded. Neuropsychological function was measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB)., Results: Compared with controls, CFS subjects exhibited significant decreases in motor speed as measured in the simple and five-choice movement segments of the CANTAB reaction time task. CFS subjects also exhibited alterations in working memory as manifested by a less efficient search strategy on the spatial working memory task, fewer % correct responses on the spatial recognition task, and prolonged latency to a correct response on the pattern recognition task. A significantly higher percentage of CFS subjects versus controls exhibited evidence of neuropsychological impairment (defined by performance 1 standard deviation below the CANTAB normative mean) in tasks of motor speed and spatial working memory. Impairment in CFS subjects versus control subjects ranged from 20% versus 4.8% in five-choice movement time (p = .002) to 27.8% versus 10.6% in search strategy on the spatial working memory task (p = .006)., Conclusions: These results confirm and quantify alterations in motor speed and working memory in CFS subjects independent of comorbid psychiatric disease and medication usage.

Objective: To examine diurnal salivary cortisol rhythms and plasma IL-6 concentrations in persons with chronic fatigue syndrome (CFS), persons not fulfilling a diagnosis of CFS (we term them cases with insufficient symptoms or fatigue, ISF) and nonfatigued controls (NF). Previous studies of CFS patients have implicated the hypothalamic-pituitary-adrenal axis and the immune system in the pathophysiology of CFS, although results have been equivocal., Methods: Twenty-eight people with CFS, 35 persons with ISF, and 39 NF identified from the general population of Wichita, Kansas, were admitted to a research ward for 2 days. Saliva was collected immediately on awakening (6:30 AM), at 08:00 AM, 12 noon, 4:00 PM, 8:00 PM and at bedtime (10:00 PM) and plasma was obtained at 7:30 AM. Salivary cortisol concentrations were assessed using radioimmunoassay, and plasma IL-6 was measured using sandwich enzyme-linked immunosorbent assay., Results: People with CFS demonstrated lower salivary cortisol concentrations in the morning and higher salivary cortisol concentrations in the evening compared with both ISF and NF groups indicating a flattening of the diurnal cortisol profile. Mean plasma IL-6 concentrations were highest in CFS compared with the other groups, although these differences were no longer significant after controlling for BMI. Attenuated decline of salivary cortisol concentrations across the day and IL-6 concentration were associated with fatigue symptoms in CFS., Conclusions: These results suggest an altered diurnal cortisol rhythm and IL-6 concentrations in CFS cases identified from a population-based sample.

Objective: To review the evidence for overlap in the phenomenology of the Functional Somatic Syndromes (FSS). The FSS show considerable comorbidity, leading some to suggest they may be aspects of the same disorder., Methods: We conducted a selective review of peer-reviewed articles on the co-occurrence of FSS symptoms and diagnoses., Results: Considerable evidence of overlap was found at the level of symptoms, diagnostic criteria, and clinical diagnoses made., Conclusions: Phenomenological commonalities support a close relationship between the FSS, although differences remain in other domains. Whether the FSS may best be considered the same or different will depend on the pragmatics of diagnosis.

Objective: The relationship between alexithymia and real-time momentary symptom assessments has not been reported. This cross-sectional study hypothesized that alexithymia would be a predictor of somatic symptoms using three different types of symptom measurement (momentary, recall, and retrospective) in the medically unexplained illness of chronic fatigue syndrome (CFS). In addition, it was hypothesized that negative affect would be a significant mediator of the relationship between alexithymia and somatic symptoms. Finally, the relation of alexithymia to physical illness attribution (a CFS illness predictor) was explored., Methods: Participants were 111 adults with CFS. Alexithymia was assessed with the Toronto Alexithymia Scale. Momentary ratings of current symptoms and affect were recorded in electronic diaries carried for 3 weeks. Weekly recall of these momentary reports was also recorded. Retrospective measures included 6-month ratings of fatigue and pain, the Fatigue Severity Scale, the Brief Pain Inventory-Short Form, a CFS symptom measure, the Beck Depression Inventory-II, the Beck Anxiety Inventory, and an illness attribution rating., Results: Partial correlations, controlling for age and sex, yielded no significant associations between general or specific forms of alexithymia and momentary ratings of fatigue or pain. On the other hand, a significant association, partially mediated by anxiety scores, was found between a specific form of alexithymia and a retrospective pain measure. Finally, physical illness attribution was not significantly associated with alexithymia., Conclusion: Based on assessments of real-time and retrospectively measured symptoms, these data provided only modest support for the alexithymia construct as a predictor of somatic symptoms in people with CFS.

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.

Objectives: Recent academic debate has centered on whether functional somatic syndromes should be defined as separate entities or as one syndrome. The aim of this study was to investigate whether there may be significant differences in the etiology or precipitating factors associated with two common functional syndromes, irritable bowel syndrome (IBS) and chronic fatigue syndrome (CFS)., Methods: We prospectively studied 592 patients with an acute episode of Campylobacter gastroenteritis and 243 with an acute episode of infectious mononucleosis who had no previous history of CFS or IBS. At the time of infection, patients completed a baseline questionnaire that measured their levels of distress using the Hospital Anxiety and Depression scale. At 3- and 6-month follow-up, they completed questionnaires to determine whether they met published diagnostic criteria for chronic fatigue (CF), CFS, and/or IBS., Results: The odds of developing IBS were significantly greater post-Campylobacter than post-infectious mononucleosis at both 3- (odds ratio, 3.45 [95% confidence interval (CI), 1.75-6.67]) and 6- (2.22 [95% CI, 1.11-6.67]) month follow-up. In contrast, the odds for developing CF/CFS were significantly greater after infectious mononucleosis than after Campylobacter at 3 (2.77 [95% CI, 1.08-7.11]) but not 6 (1.48 [95% CI, 0.62-3.55]) months postinfection. Anxiety and depression were the strongest predictors of CF/CFS, whereas the nature of the infection was the strongest predictor of IBS., Conclusions: These results support the argument to distinguish between postinfectious IBS and CFS. The nature of the precipitating infection appears to be important, and premorbid levels of distress appear to be more strongly associated with CFS than IBS, particularly levels of depression.

Objective: The placebo response is conventionally asserted to be high in chronic fatigue syndrome (CFS) because of the latter's subjective nature and obscure pathogenesis, but no systematic review of placebo responses has been undertaken. We report such a study. Patient expectation is known to be important in the placebo response. It is also known that CFS patients attending specialist clinics often have strong physical attributions regarding causation and hence skepticism about psychological or psychiatric interventions. If so, the placebo response in CFS may be influenced by the type of intervention according to its perceived rationale. We aimed to estimate the summary placebo response in clinical trials of CFS and to determine whether intervention type influences the placebo response in CFS., Methods: We searched Medline, Embase, Cochrane Library, PsychInfo, and the references of the identified articles, and contacted experts for controlled trials (randomized or nonrandomized) of any intervention on CFS patients reporting the placebo response as a clinical improvement in physical or general outcomes. Data were extracted from the articles and validity assessment conducted by one reviewer and checked by a second. Meta-analysis and metaregression were performed., Results: The pooled placebo response was 19.6% (95% confidence interval, 15.4-23.7), lower than predicted and lower than in some other medical conditions. The meta-regression revealed that intervention type significantly contributed to the heterogeneity of placebo response (p = .03)., Conclusion: In contrast with the conventional wisdom, the placebo response in CFS is low. Psychological-psychiatric interventions were shown to have a lower placebo response, perhaps linked to patient expectations.

Objectives: We compared the effects of acetylcarnitine, propionylcarnitine and both compounds on the symptoms of chronic fatigue syndrome (CFS)., Methods: In an open, randomized fashion we compared 2 g/d acetyl-L-carnitine, 2 g/d propionyl-L-carnitine, and its combination in 3 groups of 30 CFS patients during 24 weeks. Effects were rated by clinical global impression of change. Secondary endpoints were the Multidimensional Fatigue Inventory, McGill Pain Questionnaire, and the Stroop attention concentration test. Scores were assessed 8 weeks before treatment; at randomization; after 8, 16, and 24 weeks of treatment; and 2 weeks later., Results: Clinical global impression of change after treatment showed considerable improvement in 59% of the patients in the acetylcarnitine group and 63% in the propionylcarnitine group, but less in the acetylcarnitine plus propionylcarnitine group (37%). Acetylcarnitine significantly improved mental fatigue (p =.015) and propionylcarnitine improved general fatigue (p =.004). Attention concentration improved in all groups, whereas pain complaints did not decrease in any group. Two weeks after treatment, worsening of fatigue was experienced by 52%, 50%, and 37% in the acetylcarnitine, propionylcarnitine, and combined group, respectively. In the acetylcarnitine group, but not in the other groups, the changes in plasma carnitine levels correlated with clinical improvement., Conclusions: Acetylcarnitine and propionylcarnitine showed beneficial effect on fatigue and attention concentration. Less improvement was found by the combined treatment. Acetylcarnitine had main effect on mental fatigue and propionylcarnitine on general fatigue.

Objectives: To determine prospective changes in clinical status related to chronic fatigue over an 18-month period, and to test demographic and clinical predictors of outcome., Methods: A cohort of 100 patients with unexplained chronic fatigue (UCF), which encompasses both chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF), completed questionnaire measures and medical and psychiatric evaluations on four occasions, each six months apart., Results: Approximately 21% of the sample did not meet criteria for either CFS or ICF at their last research appointment 1.5 years after their index visit. Vitality increased over time, and physical functioning tended to improve, but UCF symptoms did not decrease significantly. Less education, being unemployed, worse mental health, more use of sedating and antidepressant medications, and more somatic attributions for their symptoms were associated with worsening symptom severity over time. Older age, current depression, and more somatic attributions predicted worsening physical functioning. Better mental health, less use of sedating medications, and fewer somatic attributions for illness were significant predictors of increases in vitality., Conclusions: Demographic and clinical variables predict outcomes over time among a cohort of patients with unexplained chronic fatigue.

Objective: Our objective was to review and compare, with meta-analytic methods, observational studies on the association of medically unexplained physical symptoms, anxiety, and depression with special emphasis on healthy and organically ill control groups and on different types of symptoms, measures, and illness behavior., Methods: A search of MEDLINE and PsycLIT/PsycINFO for abstracts from 1980 to April 2001 was performed; principal investigators in the field were contacted and article reference lists were used to retrieve additional relevant articles. Two hundred forty-four studies were included on the basis of consensus ratings if they fulfilled seven of eight inclusion criteria pertaining to diagnostic accuracy and statistical appropriateness. Five hundred twenty-two studies were deferred or excluded. We focused specifically on the four functional somatic syndromes for which there were sufficient numbers for meta-analytic integration: irritable bowel syndrome (IBS), nonulcer dyspepsia (NUD), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Data were extracted independently by two authors according to a prespecified coding manual with up to 70 parameters per study., Results: Effect sizes for the association of the four functional somatic syndromes with depression and anxiety were of moderate magnitude but were highly significant statistically when compared with healthy persons and controls with medical disorders of known organic pathology. Moreover, this association was significant whether depression was measured with or without somatic items. Chronic fatigue syndrome is characterized by higher scores of depression, fibromyalgia by lower scores of anxiety than irritable bowel syndrome. Consulting behavior and severity of somatization is related to higher levels of anxiety and depression., Conclusions: Meta-analytic integration confirms that the four functional somatic syndromes (IBS, NUD, FM, CFS) are related to (but not fully dependent on) depression and anxiety. At present, there is only limited meta-analytic evidence for the same sort of association for medically unexplained physical symptoms in general. In view of the relative independence from depression and anxiety, classification and treatment of these symptoms and syndromes as "common mental disorders" does not seem fully appropriate.

Objective: Evidence of comorbidity among unexplained illness syndromes raises the possibility that all are variants of a single functional disorder, leading some to suggest that separate case definitions for chronic fatigue syndrome (CFS), fibromyalgia (FM), and multiple chemical sensitivity (MCS) may be unnecessary. Our objective was to determine whether discrete diagnostic labels provide useful information about physical functioning, symptom severity, and risk of psychiatric illness., Methods: The sample consisted of 163 consecutive female referrals with CFS enrolled at a tertiary clinic. Each participant was retrospectively assigned to one of four groups: CFS only, CFS/FM, CFS/MCS, and CFS/FM/MCS. At enrollment, participants gave their history, underwent a physical examination and a standardized psychiatric interview (Diagnostic Interview Schedule), and answered self-report questionnaires., Results: Additional unexplained syndromes were prevalent: 37% met criteria for FM, and 33% met criteria for MCS. With the exception of FM-related pain and disability, there were few differences between the CFS only and CFS with comorbid illness groups. Patients with additional illness were more likely to have major depression and a higher risk of psychiatric morbidity compared with patients in the CFS only group (p <.01). Rates of lifetime depression increased from 27.4% in the CFS only group to 52.3% in the CFS/FM group, 45.2% in the CFS/MCS group, and 69.2% in the CFS/FM/MCS group., Conclusions: The prevalence of comorbid illness in the present CFS sample and the failure to find widespread differences in symptom severity can be seen as support for the single syndrome hypothesis. On the other hand, the existence of discrete syndromes could not be ruled out because of reliable differences between CFS and CFS/FM. Increasing comorbidity was associated with a corresponding increase in risk of major depression.

Objective: The purposes of this study were to compare functional imaging under control and experimental conditions among patients with chronic fatigue syndrome (CFS) and healthy persons and to examine perceived and objective performance on a test of attention and working memory previously found to be difficult for persons with CFS., Methods: Single-photon emission computerized tomography scans were completed on 15 subjects with CFS and 15 healthy persons twice: at rest and when performing the Paced Auditory Serial Addition Test (PASAT)., Results: No group differences were found for performance on the PASAT despite CFS subjects' perceptions of exerting more mental effort to perform the task than healthy subjects. Inspection of the aggregate scans by group and task suggested a pattern of diffuse regional cerebral blood flow among subjects with CFS in comparison with the more focal pattern of regional cerebral blood flow seen among healthy subjects. Between-group region-of-interest analysis revealed that although CFS subjects showed less perfusion in the anterior cingulate region, the change in CFS subjects' activation of the left anterior cingulate region during the PASAT was greater than that observed for healthy subjects. The differences were not attributable to lesser effort by the subjects with CFS, confounding effects of mood perturbation, or to poorer performance on the experimental task., Conclusions: Further research regarding CFS subjects' diffuse cerebral perfusion and its relationship to inefficient neuropsychological performance is warranted.

Objectives: Subtle alterations of the hypothalamic-pituitary-adrenal (HPA) axis in chronic fatigue syndrome (CFS) have been proposed as a shared pathway linking numerous etiological and perpetuating processes with symptoms and observed physiological abnormalities. Because the HPA axis is involved in the adaptive responses to stress and CFS patients experience a worsening of symptoms after physical and psychological stress, we tested HPA axis functioning with three centrally acting stress tests., Methods: We used two procedures mimicking real-life stressors and compared them with a standardized pharmacological neuroendocrine challenge test. CFS patients were compared with healthy control subjects regarding their cardiovascular and endocrine reactivity in a psychosocial stress test and a standardized exercise test, and their endocrine response in the insulin tolerance test (ITT)., Results: Controlling for possible confounding variables, we found significantly lower ACTH response levels in the psychosocial stress test and the exercise test, and significantly lower ACTH responses in the ITT, with no differences in plasma total cortisol responses. Also, salivary-free cortisol responses did not differ between the groups in the psychosocial stress test and the exercise test but were significantly higher for the CFS patients in the ITT. In all tests CFS patients had significantly reduced baseline ACTH levels., Conclusions: These results suggest that CFS patients are capable of mounting a sufficient cortisol response under different types of stress but that on a central level subtle dysregulations of the HPA axis exist.

Objective: Subtle dysregulations of the hypothalamus-pituitary-adrenal axis in chronic fatigue syndrome have been described. The aim of this study was to examine the negative feedback regulations of the hypothalamus-pituitary-adrenal axis in chronic fatigue syndrome., Methods: In 21 patients with chronic fatigue syndrome and 21 healthy control subjects, awakening and circadian salivary free cortisol profiles were assessed over 2 consecutive days and compared with awakening and circadian salivary free cortisol profiles after administration of 0.5 mg of dexamethasone at 11:00 PM the previous day., Results: Patients with chronic fatigue syndrome had normal salivary free cortisol profiles but showed enhanced and prolonged suppression of salivary free cortisol after the administration of 0.5 mg of dexamethasone in comparison to the control subjects., Conclusions: Enhanced negative feedback of the hypothalamus-pituitary-adrenal axis could be a plausible explanation for the previously described alterations in hypothalamus-pituitary-adrenal axis functioning in chronic fatigue syndrome. Because similar changes have been described in stress-related disorders, a putative role of stress in the pathogenesis of the enhanced feedback is possible.

Objective: This study examined predictors of fatigue severity and predictors of continued chronic fatigue status at wave 2 follow-up within a random, community-based sample of individuals previously evaluated in a wave 1 prevalence study of chronic fatigue and chronic fatigue syndrome that originally took place between 1995 and 1997., Methods: Wave 1 data were from a larger community-based prevalence study of chronic fatigue syndrome. In the present study, a second wave of data were collected by randomly selecting a sample of participants from the wave 1 sample of 18,675 adults and readministering a telephone screening questionnaire designed to assess symptoms of chronic fatigue syndrome., Results: Findings revealed that wave 1 fatigue severity was a predictor of fatigue severity at wave 2 in the overall sample of individuals with and without chronic fatigue. In the smaller sample of individuals with chronic fatigue, wave 1 fatigue severity, worsening of fatigue with physical exertion, and feeling worse for 24 hours or more after exercise significantly predicted continued chronic fatigue status (vs. improvement) at wave 2 follow-up., Conclusions: These findings underscore the prognostic validity of postexertional malaise in predicting long-term chronic fatigue and also highlight the importance of using population-based, representative random samples when attempting to identify long-term predictors of chronic fatigue at follow-up.

Objective: The purpose of this study was to compare the cardiovascular responses of patients with chronic fatigue syndrome (CFS) to healthy control subjects when performing stressful cognitive tasks before and after strenuous exercise., Method: Beat-by-beat blood pressure and electrocardiogram were recorded on 19 women with CFS and 20 healthy nonexercising (ie, sedentary) women while they performed cognitive tests before, immediately after, and 24 hours after incremental exercise to exhaustion., Results: Diminished heart rate (p <.01) and systolic (p <.01) and diastolic (p <.01) blood pressure responses to stressful cognitive testing were seen in patients with CFS when compared with healthy, sedentary controls. This diminished stress response was seen consistently in patients with CFS across three separate cognitive testing sessions. Also, significant negative correlations between self-ratings of CFS symptom severity and cardiovascular responses were seen (r = -0.62, p <.01)., Conclusions: Women with CFS have a diminished cardiovascular response to cognitive stress; however, exercise did not magnify this effect. Also, the data showed that the patients with the lowest cardiovascular reactivity had the highest ratings of CFS symptom severity, which suggests that the individual response of the patient with CFS to stress plays a role in the common complaint of symptoms worsening after stress.

Objective: The objective of this study was to examine whether inappropriate cardiovascular responses to stressors may underlie symptoms in Gulf War veterans with chronic fatigue., Methods: Psychophysiological stress testing was performed on 51 Gulf War veterans with chronic fatigue (using the 1994 case definition of the Centers for Disease Control and Prevention) and 42 healthy veterans. Hemodynamic responses to cold pressor, speech, and arithmetic stressors were evaluated using impedance cardiography., Results: Veterans with chronic fatigue had diminished blood pressure responses during cognitive (speech and arithmetic) stress tests due to unusually small increases in total peripheral resistance. The cold pressor test, however, evoked similar blood pressure responses in the chronic fatigue and control groups. Low reactivity to cognitive stressors was associated with greater fatigue ratings among ill veterans, whereas an opposite relation was observed among healthy veterans. Self-reported neurocognitive decline was associated with low reactivity to the arithmetic task., Conclusions: These results suggest a physiological basis for some Gulf War veterans' reports of severe chronic fatigue. A greater deficit with responses processed through cerebral centers, as compared with a sensory stimulus (cold pressor), suggests a defect in cortical control of cardiovascular function. More research is needed to determine the specific mechanisms through which the dissociation between behavioral and cardiovascular activities identified in this study may be contributing to symptoms in Gulf War veterans.

Objective: The predictive power of partners' responses to illness behavior for illness outcomes was investigated among couples in which one person had chronic fatigue syndrome (CFS)., Methods: One hundred nineteen participants who met case-definition criteria for CFS and were living with a significant other (SO) completed self-report measures of relationship satisfaction, responses of their SO to fatigue symptoms, and outcome measures of fatigue and functional status., Results: The results indicated that more frequent solicitous SO responses to illness behavior were predictive of greater fatigue-related severity and bodily pain. Solicitous SO responses to fatigue behavior were particularly influential in the context of a satisfactory relationship. In highly satisfactory relationships, solicitous SO responses were associated with significantly greater fatigue severity and fatigue-related disability than in relationships characterized by low or average satisfaction., Conclusions: Solicitous SO responses to CFS-related symptoms are associated with poorer patient outcomes, especially in the context of a satisfactory intimate relationship. Because of the cross-sectional nature of the study, the direction of effects cannot be interpreted unambiguously. SOs may be inadvertently positively reinforcing illness-related behavior: Solicitous partners may help the patient more with tasks of daily living, thereby decreasing the patient's activity level, which may lead to deconditioning and disability. Alternatively, patients with more severe symptoms and disability may present more opportunities for concerned SO responses, which again may be heightened in the context of a caring, satisfactory relationship. In either case, the results suggest that additional research on the role of solicitous SO responses is warranted.

Objective: The purpose of this study was to describe the sequence of psychosocial events and infections preceding the onset of chronic fatigue syndrome (CFS). This information was related to the temporal development of crucial symptoms in relation to the onset of, namely, fatigue, sadness, irritability, pain, and feeling of fever., Methods: A personal interview was conducted in 46 patients (mean age, 39.5 years; SD, 9 years) who fulfilled international CFS criteria. These patients were matched with regard to age and gender to 46 carefully matched control subjects. Twenty-three percent of the study subjects were men, and 77% were women. The patient at first identified the month that coincided with the onset of CFS. Similarly, each control subject was asked to identify a "very difficult period" within approximately the same period as the patient with whom the control subject was matched. A list of 14 different life events was perused. Participants were asked to identify for each month whether each of the listed events had occurred. Furthermore, they were asked to rate the importance of the events they had experienced. In addition, for each of the cardinal symptoms (fatigue, sadness, irritability, pain, and feeling of fever) and for each month, the subjects were asked to rate, on a visual analogue scale, the symptom intensity. Also, the number of infections was noted., Results: A statistically significant group difference in fatigue intensity existed during the period 4 to 10 months before the onset of CFS. During the 3 months preceding the diagnosis for the CFS patients or the peak of the crisis for the control group, there was a dramatic rise in fatigue in both groups. The CFS group reached a much higher fatigue level, which leveled off somewhat during the first year of follow-up but still remained very high in comparison with the control group, which reached precrisis levels 4 months after the peak. Similar patterns were observed for fever and pain. With regard to sadness and irritability, no group difference was observed during the period preceding the crisis. In the patient group, the level stayed high throughout the whole first year of follow-up, whereas a slow return started in the control group; precrisis levels were reached after 1 year in this group. The prevalence ratio (CFS patients/control subjects) for negative events was around 1.0 for the periods 4 to 12 months preceding CFS but 1.9 during the quarter year preceding the onset. For infections, the prevalence ratio increased successively during the four quarters preceding CFS (from 1.4 to 2.3)., Conclusions: According to the retrospective self-reports, there were differences between the groups in fatigue, pain, and feeling of fever during the months preceding the crisis. With regard to depressive and irritable feelings, no preillness differences were reported between the groups. There was a reported excess prevalence of both infections and negative life events during the quarter year preceding the onset of CFS or crisis. Potential sources of error are discussed. These findings must be replicated in longitudinal studies.

Objective: The effects of burnout and perceived stress on early morning free cortisol levels after awakening were investigated in a group of teachers. Previous studies revealed that cortisol levels show a significant increase after awakening, with high intraindividual stability., Methods: Sixty-six teachers from local public schools (42 women and 24 men, mean age 42+/-5 years) were asked to sample saliva for cortisol analysis on 3 consecutive days. On each day, cortisol levels were measured at the time of awakening and 15, 30, and 60 minutes thereafter. On the night before the third day, subjects took 0.5 mg dexamethasone orally for testing glucocorticoid feedback inhibition. Burnout and perceived stress were measured by three different questionnaires., Results: Perceived stress correlated with increases of cortisol levels during the first hour after awakening after dexamethasone pretreatment. In addition, teachers scoring high on burnout showed lower overall cortisol secretion on all sampling days, and a higher suppression of cortisol secretion after dexamethasone administration. In the subgroup of teachers with both high levels of perceived stress and high levels of burnout, a lower overall cortisol secretion was observed on the first 2 days, with stronger increases during the first hour after awakening after dexamethasone suppression. This subgroup also showed the lowest self-esteem, the highest external locus of control, and the highest number of somatic complaints., Conclusions: These results demonstrate differential effects of burnout and perceived stress on hypothalamic-pituitary-adrenal axis regulation.

Objective: This preliminary report compares a group of chronic fatigue syndrome (CFS) patients and controls on several variables of potential significance in the etiology of CFS., Method: The lifetime prevalence of reported physical disorders was compared among 46 CFS psychiatric patients, 92 relatively physically healthy psychiatric patients (C-I), and 46 psychiatric patients selected without regard to physical health (C-II). All patients were matched on age, sex, and psychiatric diagnosis and were drawn from the same psychiatric practice. The same groups were compared on a 7-point scale of lifetime physical health by three raters independently evaluating physical health narratives of the CFS patients up to the time of onset of CFS and that of the controls up to the corresponding age., Results: The CFS patients had a significantly higher reported lifetime prevalence of irritable bowel syndrome (IBS), infectious mononucleosis-like syndromes (IM), infectious mononucleosis-like syndromes two or more times (IM x 2), and herpes (other than genital or perioral herpes) than one or both control groups. The CFS group also had a higher incidence of allergic rhinitis or asthma, IBS, IM, and IM x 2 than the combined controls. On the independent ratings, the CFS patients had significantly more impaired physical health up to the time of onset of the CFS than C-I at a comparable age., Conclusions: The findings suggest that a general health factor may be involved in the pathogenesis of some cases of CFS.

Objective: This study examines social processes that construct the course of chronic illness. Specifically, it identifies and describes mechanisms that constitute the process of role constriction in employment for individuals with chronic illness., Method: Sixty-six persons meeting the Centers for Disease Control case definition of chronic fatigue syndrome (CFS) participated in a longitudinal study involving three waves of data collection over 3 years. Qualitative and quantitative methods were combined in the research, which included face-to-face semistructured interviews, telephone interviews, and self-report questionnaires. Materials presented in this study are drawn principally from the Year 1 face-to-face and telephone interviews., Results: When patterns of symptoms and of the illness course in CFS intersect with work requirements, they impede performance and place ill individuals at risk for job loss. Persons with CFS devise and implement specific strategies to resist role constriction and remain in the work force., Conclusions: Role constriction is a social process of marginalization in chronic illness. Opposing forces of marginalization and resistance define the social course in chronic illness and suggest that chronicity can be thought of as a marginalized position in social space.

Objective: The hypothesized polysomnographic marker for depression, Rapid Eye Movement Latency (REML), was used to investigate two groups of subjects; Chronic Fatigue Syndrome (CFS)-not depressed and CFS-depressed., Method: CFS subjects were classified into depressed and not depressed groups, using the Diagnostic Interview Schedule (DIS), and subsequently were studied in a sleep laboratory to ascertain REML., Results: Short REML showed a statistically significant correlation with the depressed state in CFS subjects., Conclusion: Short REM latency is associated with depression in the CFS population.

Objective: To determine whether patients with "pure" chronic fatigue syndrome (neurasthenia) have sleep abnormalities which may contribute to subjective measures of daytime fatigue., Method: Sleep characteristics of 20 patients meeting research criteria for chronic fatigue syndrome (CFS) but not depression, anxiety, or sleep disorder were compared with sleep characteristics of 20 healthy subjects matched for age and sex. Measures of sleep included a) subjective interview reports and sleep diaries and b) home-based polysomnography., Results: Patients with CFS complained of poor quality unrefreshing sleep. They also napped during the day. Polysomnograph data showed no difference in actual nocturnal sleep time between the two groups although patients with CFS spent significantly longer in bed (p < .01), slept less efficiently (p < .03), and spent longer awake after sleep onset (p < .05). The polysomnographs of seven patients with CFS and one healthy subject were regarded as significantly abnormal. Five patients and one healthy subject had difficulty maintaining sleep. One patient had a disorder of both initiating and maintaining sleep and one patient woke early., Conclusions: Patients with "pure" CFS complain of unrefreshing sleep but only a minority have a clearly abnormal polysomnograph. The most common abnormality is of long periods spent awake after initial sleep onset. Although sleep abnormalities may play a role in the etiology of CFS, they seem to be unlikely to be an important cause of daytime fatigue in the majority of patients. However, pharmacological and behavioral methods that improve sleep quality may be an important component of a pragmatically based treatment package for patients who do have abnormal sleep.

Objective: Patients with chronic fatigue syndrome (CFS) commonly report problems with attention, memory, learning, and speed of cognitive processing. This study attempted to evaluate these complaints using objective test criteria., Method: A test battery composed of six tests assessing these cognitive functions was given on two consecutive days. Twenty CFS patients were compared with 20 healthy control subjects and 14 patients with a history of major depression or dysthymia matched by age, intelligence, education level, and sex., Results: Compared with control subjects, CFS patients consistently scored lower on tests in which motor and cognitive processing speeds were a critical factor, eg, reaction-time tasks. They also had more difficulty on working-memory tests in which rapid cognitive processing speed is also an important factor. The effort made on the first day of testing did not result in a decline in cognitive function on the following day. CFS patients did not qualify as having affective disorder by several different diagnostic criteria. Nonetheless, CFS patients' test performances did not differ from patients with a history of major depression or dysthymia., Conclusions: It is concluded that, although CFS and major depression and dysthymia have distinct clinical features, these disorders have slowed motor and cognitive processing speed in common.

This study was conducted to examine the rates of somatization disorder (SD) in the chronic fatigue syndrome (CFS) relative to other fatiguing illness groups. It further addressed the arbitrary nature of the judgments made in assigning psychiatric vs. physical etiology to symptoms in controversial illnesses such as CFS. Patients with CFS (N = 42), multiple sclerosis (MS) (N = 18), and depression (N = 21) were compared with healthy individuals (N = 32) on a structured psychiatric interview. The SD section of the Diagnostic Interview Schedule (DIS) III-R was reanalyzed using different criteria sets to diagnose SD. All subjects received a thorough medical history, physical examination, and DIS interview. CFS patients received diagnostic laboratory testing to rule out other causes of fatigue. This study revealed that changing the attribution of SD symptoms from psychiatric to physical dramatically affected the rates of diagnosing SD in the CFS group. Both the CFS and depressed subjects endorsed a higher percentage of SD symptoms than either the MS or healthy groups, but very few met the strict DSM-III-R criteria for SD. The present study illustrates that the terminology used to interpret the symptoms (ie, psychiatric or physical) will determine which category CFS falls into. The diagnosis of SD is of limited use in populations in which the etiology of the illness has not been established.

The present study had two objectives: 1) to determine the characteristics that differentiated subjects with multiple chemical sensitivities (MCS), chemical sensitivities (CS), and chronic fatigue syndrome (CFS); and 2) to evaluate the psychiatric and neuropsychological complaints of these groups relative to normal controls. A cross-sectional comparison was made of the following groups matched for age, sex, and education: 1) patients whose sensitivities to multiple low level chemical exposures began with a defined exposure (MCS; N = 23); 2) patients with sensitivities to multiple chemicals without a clear date of onset (CS; N = 13); 3) patients meeting CDC criteria for Chronic Fatigue Syndrome (CFS; N = 18); and 4) normal controls (N = 18). Subjects with sensitivities to chemicals (MCS and CS) reported significantly more lifestyle changes due to chemical sensitivities and significantly more chemical substances that made them ill compared with chronic fatigue and normal controls. MCS, CS, and CFS patients had significantly higher rates of current psychiatric disorders than normal controls and reported significantly more physical symptoms with no medical explanation. Seventy-four percent of MCS and 61% of CFS did not qualify for any current Axis I psychiatric diagnosis. Chemically sensitive subjects without a defined date of onset (CS) had the highest rate of Axis I psychiatric disorders (69%). On the MMPI-2, 44% of MCS, 42% of CS, 53% of CFS, and none of the controls achieved clinically significant elevations on scales associated with somatoform disorders. With the exception of one complex test of visual memory, no significant differences were noted among the groups on tests of neuropsychological function. Standardized measures of psychiatric and neuropsychological function did not differentiate subjects with sensitivities to chemicals from those with chronic fatigue. Subjects with sensitivities to chemicals and no clear date of onset had the highest rate of psychiatric morbidity. Standardized neuropsychological tests did not substantiate the cognitive impairment reported symptomatically. Cognitive deficits may become apparent under controlled exposure conditions.

This study examined the effects of Hurricane Andrew on physical symptoms and functional impairments in a sample of chronic fatigue syndrome (CFS) patients residing in South Florida. In the months after Hurricane Andrew (September 15-December 31, 1992), 49 CFS patients were assessed for psychosocial and physical functioning with questionnaires, interviews, and physical examinations. This sample was made up of 25 CFS patients living in Dade county, a high impact area, and 24 patients in Broward and Palm Beach counties, areas less affected by the hurricane. Based on our model for stress-related effects on CFS, we tested the hypothesis that the patients who had the greatest exposure to this natural disaster would show the greatest exacerbation in CFS symptoms and related impairments in activities of daily living (illness burden). In support of this hypothesis, we found that the Dade county patients showed significant increases in physician-rated clinical relapses and exacerbations in frequency of several categories of self-reported CFS physical symptoms as compared to the Broward/Palm Beach county patients. Illness burden, as measured on the Sickness Impact Profile, also showed a significant increase in the Dade county patients. Although extent of disruption due to the storm was a significant factor in predicting relapse, the patient's posthurricane distress response was the single strongest predictor of the likelihood and severity of relapse and functional impairment. Additionally, optimism and social support were significantly associated with lower illness burden after the hurricane, above and beyond storm-related disruption and distress responses. These findings provide information on the impact of environmental stressors and psychosocial factors in the exacerbation of CFS symptoms.

This study used a brief battery of neuropsychological measures to examine the performance of patients with chronic fatigue syndrome (CFS) (N = 16) and patients in a major depressive episode (N = 23). The overall neuropsychological performance of the CFS group was not significantly different from depressed patients, and both groups scored within normal limits on most measures. Variability of neuropsychologic performance was in general unrelated to level of depressive symptoms. The results are discussed in terms of the validity of the cognitive criterion for the CFS diagnosis. Subjective complaints of cognitive dysfunction by CFS patients in light of the lack of objective evidence for the same are considered in terms of a somatic vigilance hypothesis.

An anthropological view of culture and somatic experience is presented through elaboration of the notion that illness has a social course. Contemporary anthropology locates culture in local worlds of interpersonal experience. The flow of events and processes in these local worlds influences the waxing and waning of symptoms in a dialetic involving body and society over time. Conversely, symptoms serve as a medium for the negotiation of interpersonal experience, forming a series of illness-related changes in sufferers' local worlds. Thus, somatic experience is both created by and creates culture throughout the social course of illness. Findings from empirical research on neurasthenia in China, and chronic fatigue syndrome (CFS) in the United States, corroborate this formulation. Attributions of illness onset to social sources, the symbolic linking of symptoms to life context, and the alleviation of distress with improvement in circumstances point to the sociosomatic mediation of sickness. Transformations occasioned by illness in the lives of neurasthenic and CFS patients confirm the significance of bodily distress as a vehicle for the negotiation of change in interpersonal worlds. An indication of some of the challenges anthropological thinking poses for psychosomatic medicine concludes the discussion.