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Since the publication of the case definition for chronic fatigue syndrome (CFS) in 1988 the diagnostic criteria have been revised twice in the U.S. None of the case definitions were derived empirically. As a result, there is concern regarding the sensitivity, specificity, and reliability of the criteria. The goal of the present study was to identify methods for improving the diagnostic criteria for CFS. Three groups of 15 participants each were recruited: participants with (1) CFS, (2) major depressive disorder (MDD), and (3) healthy controls. Using statistical procedures, three methods for improving the diagnostic criteria were explored: identification of new diagnostic symptoms, the use of severity ratings for symptomatology, and the identification of standardized measures that differentiate cases of CFS from other conditions. Results of the present study suggest that these three methods hold promise for improving the sensitivity, specificity, and reliability of the diagnostic criteria for CFS.

One of the main goals of classifying any disease or illness is to group together patients who have an illness that may have many manifestations, but a common underlying pathophysiological pathway (Hartz et al., 1998). The benefit of classifying patients into diagnostic categories is that it facilitates communication among clinicians/researchers, selection of treatment methods, and prediction of response to treatment. Past experience has shown that even in cases where the underlying pathophysiological pathway has not been identified, research on the etiology and treatment of the illness has been facilitated by simply classifying these illnesses as syndromes of signs and symptoms (e.g., systemic lupus erythematosus or tuburcleousis). This has been the case with chronic fatigue syndrome. Although the etiology of this illness remains unknown, researchers have been able to examine and better understand the nature of this illness primarily through the use of clinical classification approaches (i.e., classification criteria developed through clinical experience and observation). In 1988, a team of experienced clinicians led by the Centers for Disease Control and Prevention developed the first set of clinically derived diagnostic criteria for chronic fatigue syndrome. These criteria, developed through the consensus of an expert committee, provided health care professionals with the first set of systematic criteria to follow when assessing patients presenting with unexplained chronic fatigue. Shortly following the publication of the Holmes et al. (1988) case definition, researchers and clinicians in the United States became dissatisfied with this set of diagnostic criteria (Jason et al., 1997). Since then, the case definition has been revised twice: once in 1992 by a group who attended the 1991 National Institute of Allergy and Infectious Disease/National Institute of Mental Health workshop on CFS, and a second time in 1994 by the NIH/CDC CFS study group (Fukuda et al., 1994). The criteria published by the NIH/CDC CFS study group (Fukuda et al., 1994) is the current U.S. case definition for CFS. It is important to note that neither the original U.S. case definition nor the revised U.S. case definitions for CFS were derived empirically (Jason et al., 1997). Over the past 4–5 years researchers have become interested in attempting to validated the current U.S. case definition through empirical and statistical approaches. Overall, the results of these studies have suggested that there is moderate to strong empirical support for the current CFS case definition (Hartz et al., 1998 and Jason and Taylor, 2002; Jason et al., 2002a and Jason et al., 2002b; Komaroff et al., 1996 and Nisenbaum et al., 1998). There is some concern, however, regarding the sensitivity (i.e., ability to identify those who have the disease), specificity (i.e., ability to correctly identify those who do not have the disease), and diagnostic reliability of the Fukuda et al. (1994) criteria. Some CFS researchers are concerned that the specificity of the current U.S. case definition is poor (Jason et al., 1997). Even Fukuda, one of the primary authors of the U.S. case definition, has stated that the current CFS diagnostic criteria might not exclude people who have purely psychosocial stress, or many psychiatric reasons for their fatigue (Fukuda, personal communication, August 30, 1995). As a result, individuals with purely psychiatric disorders and psychological explanations for their fatigue might be included within the CFS rubric. Although it is possible for some individuals with CFS to have psychiatric problems before or after the onset of CFS, or even both, the inclusion of individuals with purely psychiatric disorders may seriously complicate the interpretation of epidemiological and treatment studies (Jason et al., 1997). One approach to improving the specificity as well as the sensitivity of the diagnostic criteria for CFS is through the development of empirically derived symptom criteria. Researchers attempting to empirically validate the current U.S. case definition have already made some initial suggestions regarding specific symptoms that should be added or removed to improve the overall sensitivity and specificity of the criteria. In a study conducted by Komaroff et al. (1996), patients meeting the major criteria of both the original CFS case definition (Holmes et al., 1988) and the most recently revised CSF case definition (Fukuda et al., 1994) were compared to healthy controls and two clinical populations with fatigue: patients with multiple sclerosis (MS), and patients with depression. Komaroff et al. (1996) examined the occurrence of the minor symptom criteria as well as the occurrence of several other medical symptoms not included in the case definition between the four study groups. Results of the study revealed that most of the minor criteria symptoms of the U.S. case definition were found to discriminate patients with CFS from patients with MS, depression, and healthy controls. However, the following three diagnostic symptoms were identified as being poor discriminators among the four study groups: muscle weakness, arthralgias, and sleep disturbances. Komaroff et al. (1996) therefore recommended that these items be omitted from future revisions of the CSF case definition. The authors also found that two additional symptoms currently not included in the case definition had good discriminatory power among the four study groups: anorexia and nausea. Komaroff et al. (1996) suggested adding these two symptoms to the case definition to improve the specificity and sensitivity of the diagnostic criteria. In a separate study, Hartz et al. (1998) examined persons with CFS and compared them to persons with idiopathic fatigue and persons with no symptoms of fatigue. Similar to Komaroff et al. (1996), Hartz and colleagues found support for the symptoms included in the current case definition. However, Hartz et al. (1998) also found additional symptoms that separated participants with CFS from participants with idiopathic fatigue and controls: frequent fever and chills, muscle weakness, and sensitivity to alcohol. Based on their findings, the authors recommended including these additional symptoms in the current U.S. case definition. Lastly, a study conducted by Jason et al., 2002b and Jason et al., 2002b found additional support for the current case definition. In comparison to controls, individuals with CFS reported significantly higher frequencies of all eight Fukuda et al. (1994) definitional symptoms. However the authors found several other symptoms that occurred with higher frequency and uniquely differentiated the CFS group from controls that are not included within the Fukuda et al. (1994) criteria. These symptoms included: shortness of breath, chest pain, dizziness after standing, skin sensations, general dizziness, dizzy moving the head, and alcohol intolerance. A second approach to improving the sensitivity and specificity of the criteria is the use symptom severity ratings. At present, the symptom criteria for the case definition are scored as either being present or absent with no consideration given to the severity of the symptoms. Research suggests that this scoring system is problematic because many of the symptoms included in the diagnostic criteria for CFS are commonly experienced by people at one time or another (Denche et al., 1996). For example, symptoms of fatigue, sore throat, headache, muscle pain, and post-exertional malaise are frequently experienced by people who have a cold or the flu. Denche et al. (1996) demonstrated the potential for control participants to be misdiagnosed with CFS when using Fukuda et al. (1994) symptom criteria alone. In a sample of healthy adults, 15% met Fukuda et al. (1994) symptom criteria for CFS (i.e., complained of four or more of the eight specified symptoms) (Denche et al., 1996). The symptoms included in the CFS case definition are also common to many other fatiguing medical illnesses and psychiatric conditions. For example, symptoms of fatigue, headache, unrefreshing sleep, muscle pain, and impaired memory and concentration frequently experienced by people with multiple sclerosis and major depression. Again, because of the degree of symptom overlap, it is very possible for a person with either MS or major depression to fulfill the symptomatic criteria of the current CFS case definition when only symptom occurrence is measured. Although many of the symptoms of CFS are common to many conditions, it is possible that the severity at which these symptoms are experienced by individuals with CFS is not. Use of symptom severity ratings with cutoff scores may therefore help to differentiate CFS from other illnesses with similar symptoms. There is preliminary evidence that the use of severity ratings may provide a way to improve the specificity of the current case definition. Jason et al. (2000) found that symptom severity ratings were useful for distinguishing individuals with CFS from individuals with a fatiguing psychiatric illness (i.e., melancholic depression). Jason et al. (2000) found when comparing the symptomatic criteria of participants with CFS to participants with melancholic depression, only one significant difference emerged between the groups. In other words, the occurrence of the Fukuda et al. (1994) symptomatic criteria was very similar between the two groups. However, when a symptom severity ratings were used, and a rating of 40 or higher was used as a scoring rule for determining whether the symptom fulfilled the diagnostic criteria, four significant differences emerged between the two groups. These results demonstrate the utility of severity ratings as a means for improving the specificity of the diagnostic criteria. Lastly, the absence of objective assessment approaches for the diagnostic criteria has generated concern regarding the reliability of the U.S. case definition. Researchers have noted that the case definition for CFS has been “frequently modified in practice because some of the criteria are difficult to interpret or to comply with” (Fukuda et al., 1994; p. 954). Because no laboratory tests or objective indicators for CFS exist, case identification depends primarily on information obtained through clinical interviews. Although the clinical interview is often an integral component to any assessment process, if the interview does not follow a standardized format, the results of the interview can be quite variable across examiners and different diagnostic conclusions may be reached (Matarazzo, 1983). One approach to improving the diagnostic reliability of the current U.S. CFS case definition is the identification of standardized measures with scoring guidelines to be used in conjunction with the clinical interview. The addition of standardized measures with scoring guidelines would likely improve the reliability of diagnostic decisions by providing clinicians with objective standards to follow when assessing the various features of this syndrome. In an effort to identify an objective method for discriminating CFS from major depression, Johnson et al. (1995) administered the Beck depression inventory (BDI) to people with CFS and people with major depression. Items from the BDI were categorized into one of four symptom categories (mood, self-reproach, somatic, and vegetative) and compared among the two groups. Significant differences were found in the qualitative nature of the symptoms endorsed on the BDI by people with CFS and people with major depression. The BDI scores of people with CFS were comprised mainly of items concerning physical complaints and somatic symptoms of fatigue. Symptoms of disturbed mood and self-reproach, two cardinal signs of depression, were not reported as frequently by the participants with CFS as by the participants with depression (Johnson et al., 1995). These findings demonstrate that while depressive symptoms are common in samples of people with CFS and depression, the types of items involved are qualitatively different. The results of this study suggest that incorporating a standardized measure, such as the BDI, into the diagnostic procedure for CFS may help clinicians distinguish cases of CFS from case of major depression. The use of other standardized measures of functioning would likely improve the diagnostic accuracy and reliability of CFS. For example, the SF-36 Health Survey (Ware and Sherbourne, 1992) is a standardized questionnaire that has been widely used to assess functioning in patients who have a variety of medical conditions. For many conditions, distinct SF-36 profiles have been identified (e.g., cardiovascular disease, major depression). Buchwald et al. (1996) have demonstrated that the SF-36 may also be a useful and reliable instrument for assessing functional status in patients with CFS as well as distinguishing such patients from patients with other fatiguing conditions. Additional studies replicating the results of the Buchwald et al. (1996) study are needed to establish a unique SF-36 profile for CFS patients. The present study was conducted to explore three methods for improving the diagnostic criteria and procedures for CFS. First, symptomatology was compared among patients with CFS, major depressive disorder (MDD), and healthy controls to explore which symptoms currently included in the case definition differentiate cases of CFS from MDD and controls, and to identify new symptoms (i.e., not currently included in the case definition) that differentiate CFS from these conditions. Second, the use of symptom severity ratings was examined as an additional means for distinguishing CFS from MDD and controls. Third, the use of two standardized measures, the BDI and SF-36 was evaluated to determine whether these instruments were useful for identifying cases of CFS and differentiating CFS from MDD and controls.