This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ciccone, D. S. Articles by Natelson, B. H. Search for Related Content PubMed PubMed Citation Articles by Ciccone, D. S. Articles by Natelson, B. H. Related Collections Musculoskeletal Pain Depression Somatoform

Comorbid Illness in Women With Chronic Fatigue Syndrome: A Test of the Single Syndrome Hypothesis

From the Departments of Psychiatry (D.S.C) and Neuroscience (B.H.N.), University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey.

Address reprint requests to: Donald S. Ciccone, Department of Psychiatry, BHSB Room E-1563, 183 South Orange Ave., Newark, NJ 07107. Email: cicconds{at}umdnj.edu

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
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.

Key Words: unexplained illness, • chronic fatigue syndrome, • fibromyalgia, • multiple chemical sensitivity, • comorbidity, • psychiatric illness.

Abbreviations: CFS = chronic fatigue syndrome;; FM = fibromyalgia;; GAD = generalized anxiety disorder;; MCS = multiple chemical sensitivity.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
In the absence of physical findings, physicians must rely on case definitions to standardize the diagnosis of medically unexplained illness. Definitions are now available for unexplained but debilitating fatigue (chronic fatigue syndrome or CFS) (1), widespread musculoskeletal pain (fibromyalgia or FM) (2), and extreme sensitivity to chemicals and other substances (multiple chemical sensitivity or MCS) (3). Each unexplained syndrome is associated with debilitating symptoms and an increased risk of psychiatric morbidity. The current consensus is that high rates of psychiatric illness, especially depression and anxiety, occur not only in CFS (4–6) but in other unexplained syndromes, including FM (7, 8) , and MCS (9).

When patients with unexplained illness undergo more thorough assessment, many are found to have additional (overlapping) syndromes. Several studies have shown that as many as 70% of CFS patients fulfill criteria for FM (10, 11) , whereas 30% to 42% meet criteria for MCS (11–13) . In a study that examined comorbidity from the standpoint of FM instead of CFS, 42% of female patients with FM also met full criteria for CFS (14).

Jason et al. (13) recently compared patients with more than one unexplained illness (N = 27) to those with a diagnosis of CFS only (N = 13), MCS only (N = 68), or FM only (N = 8). They found that patients with two or more syndromes had higher levels of pain as well as increased physical and social disability. Although this study represents a significant advance in our understanding of comorbidity in unexplained illness, it was limited by the small sample size and did not address the possibility that specific illness combinations (eg, CFS with comorbid FM) may have more or less deleterious effects than other combinations (eg, CFS with comorbid MCS). A primary goal of the present study was to overcome this limitation by increasing the sample size of illness groups to permit meaningful statistical comparisons.

Growing evidence of comorbidity among unexplained illness syndromes has led some to question whether they are, in fact, distinct diagnostic entities. Wessely et al. (15), for example, have suggested that the "similarities between them outweigh the differences." They propose to abandon the use of discrete case definitions in favor of more broadly defined categories or symptom "clusters." In their recent review article, Barsky and Borus (16) also noted striking similarities among many of these syndromes and suggested an explanatory model based on the concept of symptom amplification. According to this model, patients with CFS, FM, and MCS suffer from a common psychological tendency to somatize or misconstrue the significance of normal physical sensation. If true, discrete case definitions corresponding to distinct illness syndromes would be unnecessary.

On the other hand, one may reasonably argue that case definitions for discrete syndromes (ie, CFS, FM, and MCS) have advanced the study of medically unexplained illness. These definitions have made it possible to compare treatment outcomes, determine prevalence rates, document illness progression over time, and assess the effects of illness on quality of life. However, if Wessely et al. and Barsky and Borus are correct, one could argue that case definitions for specific unexplained syndromes are interchangeable since patients with CFS are suffering from the same underlying functional syndrome as patients with FM or MCS. We explored this issue in the present study by comparing patients with a single unexplained syndrome (CFS only) to patients with multiple unexplained syndromes. CFS patients with comorbid FM (CFS/FM) and CFS patients with comorbid MCS (CFS/MCS) were used as comparison groups. At issue was whether these illness combinations were associated with higher or lower levels of functional ability, symptom severity, and/or risk of psychiatric illness. Group comparisons were accomplished using a large clinical sample of tertiary CFS patients to ensure an adequate sample size for each unexplained illness combination. To the extent that discrete illness definitions provide useful information about patient functioning and/or risk of psychiatric illness, we may feel justified in their continued use. On the other hand, if multiple diagnostic labels provide little or no additional information, we may wish to reconsider the use of discrete illness definitions in favor of a more broadly defined functional somatic syndrome along the lines suggested by Wessely et al. (15).

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
Study Design
A consecutive series of 163 female patients satisfied diagnostic criteria for CFS and were retrospectively assigned to one of four illness groups: CFS only, CFS/FM, CFS/MCS, and CFS/FM/MCS. Patients completed an assessment battery at the time of enrollment that included a history and physical examination, a structured psychiatric interview, and self-report questionnaires. Case definitions of CFS (1), FM (2), and MCS (3) were used to diagnose unexplained illness. The study protocol was approved by the institutional review board of the New Jersey Medical School.

Study Sample
From February 1995 through April 2000, 199 referrals to the Chronic Fatigue Syndrome Cooperative Research Center met full case criteria for CFS and signed an informed consent form. We could not assess or control for the effects of gender because of the small number of males in the sample (N = 36). To eliminate this potential bias, only females were included in the study (N = 163). Patients were recruited through newspaper ads, physician referral, and a university website (www.umdnj.edu/cfsweb/cfs). In accordance with Centers for Disease Control and Prevention criteria (1), patients were excluded for any of the following reasons: medically explained fatigue (eg, diabetes, lupus, history of malignancy, etc); past or current diagnosis of major depression with psychotic features; bipolar disorder; schizophrenia; delusional disorder; dementia; anorexia; bulimia; alcohol or other substance abuse disorder within 2 years before onset of CFS and at any time after onset; severe obesity (body mass index 45); or an abnormal laboratory or other diagnostic test consistent with an exclusionary condition.

Physical Examination
A physician’s assistant, under the supervision of the second author, performed a comprehensive history and physical examination on all referrals at the time of enrollment. The objectives were to rule out medical causes of fatigue and to diagnose unexplained syndromes using standard case definitions for CFS, FM, and MCS.

Diagnostic Interview Schedule
The DIS (17) is a standardized interview developed by the National Institute of Mental Health for the purpose of diagnosing psychiatric illness. The version used in the present study was based on DSM-III-R criteria (18). All interviews were conducted by trained research assistants who were tested to ensure adequate interrater reliability.

Psychological Test Battery
The following instruments were administered at enrollment.

Medical Outcomes Study Short Form-36 (SF-36).
This 36-item instrument is used to assess functional status and quality of life in medically ill populations (19, 20) .

Multidimensional Fatigue Inventory (MFI).
This 20-item questionnaire is designed to measure five fatigue-related constructs: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity (21).

Core CFS Symptom Ratings.
This 10-item rating scale is used to assess the severity of core CFS symptoms over the past month. All physical complaints required by the 1988 CFS case definition (22) were included. Each was rated on a six-point Likert scale from 0 (not a problem) to 5 (very severe problem).

Beck Depression Inventory.
The BDI is widely used in clinical settings to screen for depression and has well-established psychometric properties (23, 24) .

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
Our first objective was to determine the pattern of diagnostic overlap among study participants (ie, the prevalence of each illness combination). Next we examined the effects of multiple illness syndromes on physical function and symptom severity. Finally we addressed the issue of psychiatric morbidity.

1. To what extent does primary CFS coexist with other medically unexplained syndromes such as FM and MCS?
Of 163 female referrals with primary CFS, 43% met diagnostic criteria for FM (N = 70) and 35% met criteria for MCS (N = 57). Only 38% of the sample (N = 62) had "pure" CFS (ie, no comorbid illness), whereas 16% met criteria for all three syndromes (N = 26). This pattern of overlap confirms that primary CFS is highly comorbid with other forms of unexplained illness. These rates lend additional support to the hypothesis that CFS does not occur in isolation but in the context of other ill-defined syndromes. Rather than confirm the presence of discrete illness categories, the present pattern of comorbidity may be construed as evidence for a "general functional somatic syndrome" (15). In the following sections we address the question of whether and to what extent discrete illness definitions convey useful diagnostic information.

2. Are patients with multiple syndromes more physically disabled than patients with CFS only? Do they report more severe physical symptoms?
We first had to determine whether the groups differed systematically with respect to demographic factors. Table 1 shows there were only minor differences in age, racial composition, and marital status. There was a statistically significant but small (just over 1 year) difference in level of education between the most and least educated groups. However, no discernible association could be detected between educational level and type of unexplained illness.

3. Are CFS patients with comorbid unexplained illness at increased risk of psychiatric disorder?
The prevalence of lifetime psychiatric disorder in each of the unexplained illness groups is shown in Table 5. Only rates of lifetime illness were analyzed owing to the relatively small number of participants with a current diagnosis. We further restricted the analysis to lifetime disorders that occurred in at least 10% of the sample. In the case of major depression, the results indicate that prevalence increased when patients suffered from more than just CFS (p < .01). In particular, the prevalence of lifetime depression in patients with CFS/FM/MCS (69%) was more than double that observed in patients with CFS only (27%). By contrast, there was no such linear relationship between number of illness syndromes and generalized anxiety disorder (GAD). Whereas GAD occurred as often in the CFS/FM group as it did in the CFS only group, it was more than three times higher in the CFS/MCS group (p < .05). This is inconsistent with the hypothesis that multiple unexplained syndromes are necessarily associated with a higher risk of psychiatric disorder. Instead the unique association between GAD and MCS raises the possibility that specific illness categories may be associated with specific psychiatric disorders. To further examine the issue of psychiatric risk, we evaluated the association between unexplained illness and two additional dependent variables: 1) axis I disorder, scored as 0 or 1 to reflect the absence or presence of one or more lifetime axis I diagnoses; and 2) number of axis I disorders, coded as 0, 1, or more than 1. As shown in Table 5, there was a higher prevalence of axis I disorders in patients who suffered from multiple illness syndromes. For example, the prevalence of psychiatric disorder in CFS/FM/MCS patients was nearly double that of CFS only patients, 85% vs. 44%, respectively. Similarly, 54% of patients with CFS/FM/MCS met DSM-III-R criteria for more than one psychiatric diagnosis, compared with only 15% of those in the CFS only group.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

The single syndrome hypothesis of Wessely et al. asserts that most unexplained physical symptoms share a common etiology and thus do not require (or justify) separate illness definitions. The pattern of diagnostic overlap observed in the present sample along with evidence of similar physical functioning in each of the separate illness groups may be construed as support for this hypothesis. Moreover, each overlapping syndrome was associated with a corresponding increment in major depression. Collectively these findings seem to be at odds with the discrete illness hypothesis, that is, the view that each unexplained syndrome has a distinct etiology. On the other hand, we also found differences between groups that are difficult to reconcile with the single syndrome hypothesis. There were, for example, notable differences between illness groups in psychiatric morbidity (eg, GAD risk) and an increased rate of gradual illness onset in FM patients compared with those without FM.

A separate but related issue concerns the relationship between unexplained illness and psychiatric morbidity. There are at least three possible reasons why patients with multiple unexplained syndromes have higher rates of psychiatric disorder: 1) additional illness burden: patients with multiple syndromes have more symptoms and/or more disability than patients with a single syndrome; 2) somatization: patients with multiple syndromes are somatizers (27, 28) ; and 3) discrete disorder: patients with CFS only have a discrete (medical) illness, whereas patients with multiple syndromes have a somatoform or functional illness. Although the present study was not designed to test these competing models, we conducted a preliminary evaluation of the illness burden hypothesis and found it lacking. Using a logistic regression model, we asked if illness burden, as measured by symptom severity, could predict lifetime depression. To provide an estimate of overall illness burden, we used all available SF-36 scales (except for mental health and role-emotional), all five MFI scales, and tender point count. Of all the predictors in the model, only tender point count was significantly associated with major depression, 1.07:1 (95% confidence interval, 1.01–1.14) (p < .05). This result shows that depression in patients with multiple syndromes is not due to the "burden" of living with more symptoms or coping with more disability.

Another reason that patients with comorbid illness have higher rates of psychiatric disorder is offered by the somatization hypothesis. Kroenke et al. (27) showed that patients who have no unexplained symptoms or only one such symptom met criteria for mood disorder far less often than those with nine unexplained symptoms (2% vs. 60%, respectively). The present results lend support to the somatization model by demonstrating a similar association between psychiatric morbidity (especially major depression) and number of unexplained syndromes. The last explanation for psychiatric morbidity is the discrete illness hypothesis. As noted above, only 27% of the CFS only group had major depression. This is consistent with the rate of depression in medically explained fatigue (29, 30) and leaves open the possibility that CFS only is a discrete entity.

Methodological limitations of the present study necessarily lessen our ability to draw firm conclusions about diagnostic utility. Although demographic characteristics of the present sample were consistent with previous CFS research (26, 31) , study participants were enrolled at a tertiary medical center and therefore likely to suffer from elevated rates of psychiatric illness on that basis alone. Recent studies by Wessely et al. (5) and others (6, 32) have shown that psychiatric illness in CFS occurs in community samples and is not an artifact of the treatment setting. However, we cannot estimate how much of the psychiatric morbidity observed in the present sample was due to treatment seeking and how much was due to unexplained illness. Because our study design was retrospective, it is also possible that group comparisons may have been influenced by factors that were not assessed. For example, differences in treatment history or medication use may have obscured differences between CFS only and multiple illness groups. A more serious omission was that diagnostic information about the present sample was limited to CFS, FM, and MCS. It is entirely possible that patients with "CFS only" met criteria for other unexplained illness syndromes that were not assessed (eg, chronic headache, whiplash, etc). These unidentified syndromes may have affected physical functioning and/or psychiatric comorbidity and confounded group comparisons. Notwithstanding these limitations, the present results show that patterns of comorbidity (or symptom overlap) provide important information about psychiatric disorder. For example, CFS patients with comorbid FM and MCS had a much higher rate of psychiatric illness than patients with CFS only (85% vs. 44%, respectively). In view of these results it may not be appropriate to single out a specific syndrome for investigation unless or until a thorough assessment of overlapping syndromes (or symptoms) has also been conducted.

	ACKNOWLEDGMENTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
Financial support was provided by National Institutes of Health (AI-32247).

	NOTES

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
Presented at the 59th Annual Scientific Meeting of the American Psychosomatic Society, March 2001, Monterey, California.

Received for publication September 21, 2001.

	REFERENCES

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 

1. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med 1994; 121: 953–9.[Abstract/Free Full Text]
2. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, Fam AG, Farber SJ, Flechtner JJ, Franklin CM, Gatter RA, Hamaty D, Lessard J, Lichtbroun AS, Masi AT, McCain GA, Reynolds WJ, Romano TJ, Russell IJ, Sheon RP. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990; 33: 160–72.[Medline]
3. Nethercott JR, Davidoff LL, Curbow B, Abbey H. Multiple chemical sensitivities syndrome: toward a working case definition. Arch Environ Health 1993; 48: 19–26.[Medline]
4. Walker EA, Katon WJ, Jemelka RP. Psychiatric disorders and medical care utilization among people in the general population who report fatigue. J Gen Intern Med 1993; 8: 436–40.[Medline]
5. Wessely S, Chalder T, Hirsch S, Wallace P, Wright D. Psychological symptoms, somatic symptoms, and psychiatric disorder in chronic fatigue and chronic fatigue syndrome: a prospective study in the primary care setting. Am J Psychiatry 1996; 153: 1050–9.[Abstract/Free Full Text]
6. Skapinakis P, Lewis G, Meltzer H. Clarifying the relationship between unexplained chronic fatigue and psychiatric morbidity: results from a community survey in Great Britain. Am J Psychiatry 2000; 157: 1492–8.[Abstract/Free Full Text]
7. Walker EA, Keegan D, Gardner G. Psychosocial factors in fibromyalgia compared with rheumatoid arthritis. I. Psychiatric diagnoses and functional disability. Psychosom Med 1997; 59: 565–71.[Abstract/Free Full Text]
8. Epstein SA, Kay G, Clauw D, Heaton R, Klein D, Krupp L, Kuck J, Leslie V, Masur D, Wagner M, Waid R, Zisook S. Psychiatric disorders in patients with fibromyalgia: a multicenter investigation. Psychosomatics 1999; 40: 57–63.[Abstract/Free Full Text]
9. Black DW, Okiishi C, Schlosser S. A nine-year follow-up of people diagnosed with multiple chemical sensitivities. Psychosomatics 2000; 41: 253–61.[Abstract/Free Full Text]
10. Goldenberg DL, Simms RW, Geiger A, Komaroff AL. High frequency of fibromyalgia in patients with chronic fatigue seen in a primary care practice. Arthritis Rheum 1990; 33: 381–7.[Medline]
11. Buchwald D, Garrity D. Comparison of patients with chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivities. Arch Intern Med 1994; 154: 2049–53.[Abstract]
12. Pollet C, Natelson BH, Lange G, Tiersky L, DeLuca J, Policastro T, Desai P, Ottenweller, Korn L, Fiedler N, Kipen H. Medical evaluation of Persian Gulf veterans with fatigue and/or chemical sensitivity. J Med 1998; 29: 101–13.[CrossRef][Medline]
13. Jason LA, Taylor RR, Kennedy CL. Chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivities in a community-based sample of persons with chronic fatigue syndrome-like symptoms. Psychosom Med 2000; 62: 655–63.[Abstract/Free Full Text]
14. Hudson JI, Goldenberg DL, Pope HG, Keck PE, Schlesinger L. Comorbidity of fibromyalgia with medical and psychiatric disorders. Am J Med 1992; 92: 363–7.[CrossRef][Medline]
15. Wessely S, Nimnuan C, Sharpe M. Functional somatic syndromes: one or many? Lancet 1999; 354: 936–9.[CrossRef][Medline]
16. Barsky AJ, Borus JF. Functional somatic syndromes. Ann Intern Med 1999; 130: 910–21.[Abstract/Free Full Text]
17. Robins LN, Helzer JE. Diagnostic Interview Schedule (DIS): version III-A. St Louis (MO): Washington University School of Medicine; 1985.
18. DSM-III-R. Diagnostic and statistical manual of mental disorders. 3rd ed revised. Washington DC: American Psychiatric Association 1987.
19. Ware JE, Sherbourne CD. The MOS 36-Item Short-Form Health Survey (SF-36): conceptual framework and item selection. Med Care 1992; 30: 473–83.[Medline]
20. McHorney CA, Ware JE Jr, Lu JFR, Sherbourne CD. The MOS 36-Item Short-Form Health Survey (SF-36). III. Tests of data quality, scaling assumptions, and reliability across diverse patient groups. Med Care 1994; 32: 40–66.[Medline]
21. Smets EMA, Garssen B, Bonke B, De Haes JC. The Multidimensional Fatigue Inventory (MFI): psychometric qualities of an instrument to assess fatigue. J Psychosom Res 1995; 39: 315–25.[CrossRef][Medline]
22. Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S, Tosato G, Zegans LS, Purtilo DT, Brown N, Schooley RT, Brus I. Chronic fatigue syndrome: a working case definition. Ann Intern Med 1988; 108: 387–9.
23. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961; 4: 561–71.
24. Beck AT, Steer RA, Garbin MG. Psychometric properties of the Beck Depression Inventory: twenty-five years of evaluation. Clin Psychol Rev 1988; 8: 77–100.
25. Jenkinson C, Coulter A, Wright L. Short Form 36 (SF-36) Health Survey questionnaire: normative data from a large random sample of working age adults. BMJ 1993; 306: 1437–40.
26. Aaron LA, Burke MM, Buchwald D. Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch Intern Med 2000; 160: 221–7.[Abstract/Free Full Text]
27. Kroenke K, Spitzer RL, Williams JBW, Linzer M, Hahn SR, deGruy FV, Brody D. Physical symptoms in primary care: predictors of psychiatric disorders and functional impairment. Arch Fam Med 1994; 3: 774–9.[Abstract]
28. Katon W, Lin E, Von Korff M, Russo J, Lipscomb P, Bush T. Somatization: a spectrum of severity. Am J Psychiatry 1991; 148: 34–40.[Abstract/Free Full Text]
29. Sullivan MJ, Weinshenker B, Mikail S, Edgley K. Depression before and after diagnosis of multiple sclerosis. Mult Scler 1995; 1: 104–8.[Medline]
30. Patten SB, Metz LM, Reimer MA. Biopsychosocial correlates of lifetime major depression in a multiple sclerosis population. Mult Scler 2000; 6: 115–20.[Abstract/Free Full Text]
31. Clark MR, Katon W, Russo J, Kith P, Sintay M, Buchwald D. Chronic fatigue: risk factors for symptom persistence in a 21/2-year follow-up study. Am J Med 1995; 98: 187–95.[CrossRef][Medline]
32. White KP, Speechley M, Harth M, Ostbye T. Co-existence of chronic fatigue syndrome with fibromyalgia syndrome in the general population. Scand J Rheumatol 2000; 29: 44–51.[CrossRef][Medline]

This article has been cited by other articles:

				K Osterberg, R Persson, B Karlson, F C. Eek, and P Orbaek Personality, mental distress, and subjective health complaints among persons with environmental annoyance Human and Experimental Toxicology, March 1, 2007; 26(3): 231 - 241. [Abstract] [PDF]

				M. Saito, H. Kumano, K. Yoshiuchi, N. Kokubo, K. Ohashi, Y. Yamamoto, N. Shinohara, Y. Yanagisawa, K. Sakabe, M. Miyata, et al. Symptom Profile of Multiple Chemical Sensitivity in Actual Life Psychosom Med, March 1, 2005; 67(2): 318 - 325. [Abstract] [Full Text] [PDF]

				Patterns of Comorbidity in Chronic Fatigue Syndrome Journal Watch Psychiatry, May 7, 2003; 2003(507): 5 - 5. [Full Text]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ciccone, D. S. Articles by Natelson, B. H. Search for Related Content PubMed PubMed Citation Articles by Ciccone, D. S. Articles by Natelson, B. H. Related Collections Musculoskeletal Pain Depression Somatoform