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ORIGINAL ARTICLES |
From the Division of Viral and Rickettsial Diseases, Viral Exanthems and Herpesvirus Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia (C.H., C.B., R.N., D.W., W.C.R.); and the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia (C.H.).
Address correspondence and reprint requests to Christine Heim, PhD, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 101 Woodruff Circle, WMB, Suite 4000, Atlanta, GA 30322. E-mail: cmheim{at}emory.edu
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
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METHODS: Identified by random-digit dialing, 2,728 households in eight regional strata were interviewed, and 7,317 respondents were screened for severe fatigue of at least 1 month duration. Identified fatigued people of age 18 to 69 years (N = 440) and a sample of nonfatigued people of the same age range (N = 444) were interviewed in detail concerning fatigue, other symptoms, and medical and psychiatric histories.
RESULTS: Weighted prevalence estimates based on interviews performed after the attacks were significantly lower compared with estimates based on interviews performed before the attacks (prolonged fatigue: 5,450 vs. 1,530/100,000, p = .010; chronic fatigue: 18,510 vs. 10,070/100,000, p = .002; chronic fatigue syndrome-like illness: 2,510 vs. 960/100,000, p = .014).
CONCLUSION: Our findings suggest decreased regional prevalence of fatiguing illnesses in the aftermath of the terrorist attacks. The causes of this effect are unknown but might involve acute psychological and physiological adaptations that modify the perception or manifestation of fatigue. Future studies should be specifically designed to scrutinize the relationship between stress and fatiguing illnesses and the mediating mechanisms of such a relationship.
Key Words: chronic fatigue syndrome, • stress, • trauma, • epidemiology.
Abbreviations: CFS = chronic fatigue syndrome;; PTSD = posttraumatic stress disorder;; CDC = Centers for Disease Control and Prevention;; PSU = primary sampling unit;; MSA = metropolitan statistical area;; SF-12 = 12-Item Short Form Health Survey.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
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Fatiguing illnesses most likely are multifactorial disorders with several etiologic variables interacting. In addition to female sex, genetic disposition, and certain personality traits or behavioral styles among other factors, physical and emotional stressors have been identified as risk factors for CFS and other ill-defined fatiguing illnesses (3). One of the earliest studies evaluated patients with CFS identified between 1989 and 1993 through a physician surveillance network and reported that patients with CFS were significantly more likely to report a history of life stress, repeated infections, or surgery when compared with randomly selected matched controls. The association between stress and CFS was most marked in those cases with gradual onset of the illness (4). A small number of epidemiological or clinical studies have evaluated the association between severe stress or trauma and CFS or other fatiguing illnesses. For example, one study evaluating tertiary care patients found that patients with CFS more frequently reported various types of abusive victimization starting in childhood and persisting throughout adulthood compared with controls (5). In a population-based study of fatiguing illnesses, experiences of childhood abuse were identified as significant predictors of several fatiguing illnesses and accounted for comorbidity between these illnesses and anxiety disorders, namely posttraumatic stress disorder (PTSD) (6). Patients with CFS also report more exposure to an overprotective parenting style during their childhood compared with controls, which can be considered an adversity as well (7). Studies in victims of abuse further document that such experiences, particularly when experienced early in life, are associated with increased levels of later onset fatigue and pain, as well as depression and anxiety (8,9). Several studies report elevated rates of CFS in Gulf War veterans, and CFS is associated with high rates of combat-related PTSD in these veterans (10,11). Our group reported that self-reported chemical, emotional, and physical stressors associated with deployment were linked to the occurrence of a chronic multisymptom fatiguing illness in Gulf War veterans (12). In sum, it appears that severe or chronic stress is associated with increased risk for fatiguing illnesses. Stress likely interacts with other risk factors in influencing central nervous, neuroendocrine, and immune systems, resulting in functional changes that lead to fatigue and associated symptoms, such as sleep disruption, cognitive impairment, and pain (13).
Although these studies support that past chronic adversity may induce vulnerability for later onset of fatiguing illnesses, little is known about the immediate effects of an acute trauma on these illnesses. One study reports that exposure to Hurricane Andrew induced relapses of CFS and symptom exacerbations in a sample of 49 patients with CFS living in South Florida. The extent of individual emotional and behavioral stress responses was the single and strongest predictor of the likelihood and severity of the relapse and functional impairment within 4 months after the hurricane (14). The terrorist attacks of September 11, 2001, represented a major national trauma that posed significant distress on the US population and may serve as a model to evaluate the effect of stress on public health. One study conducted shortly after the attacks found that more than 90% of adults throughout the country reported stress, and 44% had at least one substantial symptom of distress (15). Estimates from a Web-based survey of 3496 adults suggest that 17% of the respondents showed posttraumatic stress symptoms at 2 months after the attacks, and 5.8% showed these symptoms at 6 months after the attacks (16). Other studies documented markedly elevated rates of PTSD and depression in the New York area after September 11, 2001 (17,18). It was also reported that in the immediate aftermath of the attacks, 11% of the US population reported sleep disturbances (15,19). Raphael et al. (20) reported that levels of widespread pain, as well as joint, bone, or muscle pain were increased 5 to 6 months after the attacks compared with before the attacks in a community sample of 1,312 women of the New York/New Jersey metropolitan area. Although the terrorist attacks imposed significant distress on the population and most studies have found a positive association with a variety of symptoms or syndromes frequently associated with CFS, it has also been reported that levels of fatigue decreased in New York/New Jersey in the wake of the attacks (20). Taken together, the relationship between acute severe stress and fatiguing illnesses remains obscure.
The Centers of Disease Control and Prevention (CDC) conducted a multigeographical pilot study to test the feasibility of a survey to estimate the prevalence of fatiguing illnesses in the United States from July through December 2001. Coincidentally, the attacks of September 11, 2001, happened after approximately half of the survey was conducted. Because these terrorist attacks represented a national trauma and severe stress or trauma is considered to be a risk factor for fatiguing illnesses, we used data obtained during this pilot survey to estimate the impact of the terrorist attacks on the regional prevalence of fatiguing illnesses. To this end, we compared regional prevalence rates of fatigue estimated from the sample interviewed before the attacks with prevalence rates estimated from the sample interviewed after the attacks. Although comparison of two cross-sectional samples does not allow for the direct inference that any changes in prevalence rates are a result of the terrorist attacks, the objectives of this exploratory analysis were to increase insight into the potential associations between acute severe stress and fatiguing illnesses and to determine the necessity for implementing preventive measures of fatiguing illnesses after similar events in the future. In addition, findings from this analysis are useful in generating hypotheses for future studies specifically designed to evaluate relationships between stressors and fatigue, including the identification of mechanisms underlying such relationships.
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MATERIALS AND METHODS |
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Study Design
The study design of the National Pilot Survey is described in detail in Bierl et al. (21). The survey used a stratified 2-stage cluster design with 2 phases, similar to our previous study of fatiguing illnesses in the general population of Wichita, Kansas (22). Briefly, the first stage of sampling selected a primary sampling unit (PSU) in each stratum, and the second stage drew a sample of telephone numbers for each PSU. Using random-digit dialing, phase 1 of data collection screened households for people identified as fatigued for 
1 month. Phase 2 was composed of detailed telephone interviews with people identified as fatigued and with a random sample of persons identified as nonfatigued. To examine regional and metropolitan differences, we constructed strata from statistical areas defined by the US Census. Each of the four US Census regions (Northeast, Midwest, South, and West) was further stratified into metropolitan statistical areas (MSAs) and non-MSA counties. From each of the eight strata, we randomly selected a PSU, either an MSA or a non-MSA county (as appropriate). The eight PSUs selected represented urban (ie, Buffalo-Niagara Falls, NY; Chicago, IL; Baton Rouge, LA; Oakland, CA) and rural regions (ie, Franklin County, PA; Ripley County, IN; Monroe County, GA; Chaves County, NM).
Phase 1: Telephone Screening Interviews
In each selected household, we screened a household informant who was at least 18 years old. The informant enumerated individual household members and reported on their age, sex, and race, and whether they were currently suffering from severe fatigue, extreme tiredness, or exhaustion that had lasted 1 month or longer.
Phase 2: Detailed Telephone Interviews
Household residents identified with fatigue 1 month were contacted for detailed interviews. We also conducted detailed interviews on a random sample of nonfatigued subjects, which were used to estimate prevalence rates and were needed to compare demographic characteristics of fatigued and nonfatigued samples. All participants were adults 18 to 69 years old.
Detailed Interview Assessments
We used a computer-assisted telephone interviewing system. Trained interviewers read questions displayed on a screen to respondents and entered responses directly into the database. Software automatically performed range and logic checks on the entered data and displayed the next question. The detailed interview included questions on demographics and fatigue characteristics, including presence of fatigue, duration, presence of concomitant symptoms, and medical/psychiatric history. For example, some of the questions were, "Are you currently suffering from severe fatigue, extreme tiredness, or exhaustion that has been present for a period of one month or longer?" "When did this fatiguing illness first begin?" "Did this fatiguing illness begin more than 6 months ago?" and "Most of the time, does rest make your fatigue a lot better?" The interview was developed by the CDC (22). Using data obtained in our previous studies in Wichita (22), we performed exemplary analyses to validate the instrument by comparing responses to the telephone survey questions with scores in the Multidimensional Fatigue Inventory (23). These analyses confirmed adequate validity of the instrument (Wagner et al., Personal communication, April 2004). In addition, the telephone interview included the 12-Item Short Form Health Survey (SF-12; QualityMetric, Lincoln, RI), which is designed to measure health-related quality of life (24).
Classification of Fatigue Status
Respondents reporting fatigue lasting at least 1 month were considered fatigued and stratified into 3 groups: a) prolonged fatigue, ie, those whose fatigue lasted between 1 and 6 months; b) chronic fatigue, ie, those who reported fatigue of at least 6 months duration but with insufficient symptoms or fatigue severity to meet the case definition of CFS; and c) CFS-like, i.e., respondents whose reported symptoms and fatigue severity met the case definition of CFS. The case definition criteria include fatigue lasting at least 6 months that was not alleviated by rest, 4 of the 8 CFS defining symptoms, and no reported medical or psychiatric exclusions (2). Subjects were excluded from being classified as having CFS-like illness if they reported any of the following conditions: cancer within 5 years of the interview, emphysema, chronic hepatitis, rheumatoid arthritis, acquired immune deficiency syndrome, lupus or Sjögren syndrome, multiple sclerosis, organ transplantation, and pregnancy or major surgery within the past year. Subjects were also excluded if they reported to have been diagnosed with lifetime bipolar disorder or schizophrenia, bulimia, or anorexia within the past 5 years, and alcohol or substance abuse disorder within 2 years. We here use the term CFS-like because CFS can be diagnosed only after a clinical evaluation is performed. All 3 fatigue categories were analyzed as discrete groups, and each subject was counted only in the most restrictive category that applied.
Date of Interviews
The date of each screening and detailed interview was recorded automatically. Based on these data, we created 2 categories of people: people who underwent the detailed interview before September 11, 2001, versus people who underwent the detailed interview after the events.
Statistical Analyses
Data from surveys often involve sampling weights, which are necessary to maintain the relation between the survey and the population (25). In our study, each household received a base sampling weight that reflected the probability of selection of the PSU and selection of the household telephone number within the PSU (21). The final household sampling weight incorporated adjustments for multiple residential lines, nonresponse, and households without telephones. For nonfatigued people who completed detailed interviews, the person-level weight was determined by the household weight and the person’s probability of selection. For fatigued people, all of whom were selected with certainty, the person-level weight for the detailed interview equaled the household weight. Prevalence estimates were based on weighted data. Weighted prevalences and weighted Pearson 
2 were calculated by using STATA 7.0 (Stata Corp., College Station, TX). Using these tests, we compared weighted prevalence estimates from detailed interviews performed before September 11, 2001, with weighted prevalence estimates from detailed interviews performed after the attacks, and we also compared responses to the SF-12. Statistical significance was set at p < .05. Confidence intervals for prevalences were constructed by using a logit transformation (hence, the lower endpoint was always greater than 0).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
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1 month, and 6,573 were nonfatigued.
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Detailed interviews commenced on August 8, 2001. A total of 383 interviews (43%) were completed before and 501 interviews (57%) were completed after the attacks. The detailed telephone interviews were completed by December 16, 2001. Subjects interviewed before and after September 11, 2001, were similar with respect to age, sex, race, Hispanic ethnicity, annual income, and education. The response rate for the screening interview dropped after September 11, 2001, compared with before the attacks, although the difference was not statistically significant (from 97.2% to 96.7%). The response rate for the detailed interview dropped significantly after the attacks (from 79.9% to 73.6%; 2 = 6.46; df = 1; p = .011).
Weighted Prevalence of Fatiguing Illnesses and SF-12 Responses Before and After September 11, 2001
As shown in Table 1, the prevalence of fatiguing illnesses before and after September 11, 2001, decreased significantly for all fatigue groups. Prevalence of prolonged fatigue decreased from 5,450 to 1,530 per 100,000 persons (p = .010). Prevalence of chronic fatigue decreased from 18,510 to 10,070 per 100,000 persons (p = .002). Prevalence of CFS-like symptoms decreased from 2,510 to 960 per 100,000 persons (p = .014). To provide further substantiation of the observed effect, we compared biweekly prevalence rates for each fatigue category before and after the attacks. Prevalence rates did not significantly differ before the attacks (p values ranged from 0.1301 to 0.6524) and were consistently lower over biweekly periods after the attacks. The effects of the attacks on prevalence rates were stronger in urban than in rural regions, although there were no significant differences in rate changes between these regions.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
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These findings are different from those of Lutgendorf et al. (14), who reported that exposure to Hurricane Andrew in a small clinical sample of patients with CFS induced relapses and exacerbations of CFS within 4 months. However, we studied a population sample rather than one tertiary care clinic. In addition, there are marked differences in the stressor characteristics and the immediate effects of the stressor on the personal life between the two studies. Hurricane Andrew represented an acutely threatening event with rapid termination of the threat and multiple actual consequences and required actions in the community. In contrast, the terrorist attacks of September 11, 2001, might have posed a potentially ongoing threat because of anticipations of further events and a general sense of insecure conditions, but no immediate consequence to a large part of the study population. Such differential stressor characteristics may be associated with differential psychological and physiological adaptations (26). Indeed, our findings are similar to those of another community study that found decreased fatigue levels after September 11, 2001 (20). Interestingly, an earlier study in Israeli patients with multiple sclerosis, performed during a period of increased threat of missile attacks during the Persian Gulf War, found that patients experienced significantly fewer relapses during the threat and the following 2 months than during the preceding 2 years (27). Multiple sclerosis is a multifactorial illness that is associated with neurocognitive, neuroendocrine, and immune alterations, similar to CFS (28).
It should be noted that the time frame and design of the present survey did not allow for detection of new incident cases or relapses of chronic fatigue and CFS-like illness as a potential consequence of the attacks. Such estimates would have required a longitudinal follow-up study design of longer duration in a larger sample (22,29). Specifically, the interviews ended in December 2001 (
3 months after the attacks), whereas a diagnosis of chronic fatigue and CFS-like illness requires a symptom duration of at least 6 months. Nevertheless, prevalence estimates after the attacks should have included at least some new incident or relapsing cases in the prolonged fatigue category (1 month). Given that in a previous survey, the association between stress and fatigue was most pronounced in cases with gradual onset (4), it is possible that increases in new incident or relapsing cases of fatigue related to the attacks of September 11, 2001, would have affected prevalence rates at a later time.
What could explain our findings of decreased prevalence rates in the sample interviewed after the attacks? Both, study methodology as well as psychological and psychobiological processes must be considered. In our study, response rates of participation in the detailed telephone interviews dropped significantly after the attacks. Although response rates after the attacks were still reasonably high to estimate regional prevalence rates for fatiguing illnesses, we cannot exclude the possibility that there might have been an interaction effect between fatigue status and response rates. In other words, it is possible that subjects who were fatigued were less willing to participate in the interviews after the attacks. Such an interaction effect would result in decreased prevalence estimates of fatigue after the attacks. Controlling for such interaction effects would require data on fatigue status of nonparticipants, which is unavailable. It is also possible that the terrorist attacks caused psychological processes that lead to altered reporting or perception of symptoms of fatigue. Thus, experiencing the terrorist attacks and subsequent additional threats, as well as reflecting about the attacks, might have put personal problems into perspective, and people might have developed a tendency to count their blessings rather than complain about health problems. Similarly, experiencing the events might have been a powerful distraction that directed attention away from perceived symptoms, leading to lower rates of fatigue in the immediate aftermath of the attacks. Distraction, indeed, is a technique commonly and effectively used in cognitive-behavioral therapy of chronic pain or other somatic symptoms (30,31). Similarly, findings obtained from disaster psychology suggest that mass disaster is associated with profound loss and disruption of communities and that the social and environmental interactions, and the actions required to respond to the disaster, enable people to refocus from internalizing to externalizing behaviors, which might result in decreases of perceived symptoms (32).
Another explanation might be that the stress of September 11, 2001, could have induced neurobiological, physiological, and behavioral adaptations that ameliorated fatigue and other symptoms of CFS. It is well known that acute stress induces a fight-and-flight response that prepares the organism for coping with the challenge. Sympathoadrenal activation results in increased release of epinephrine and norepinephrine and in changes in blood flow to a variety of organs, reflecting an alarm reaction. Activation of the hypothalamic-pituitary-adrenal axis results in increased secretion of glucocorticoids, which have manifold effects to mobilize energy and regulate immune reactions to stress tightly. In the brain, stress responsive neurotransmitter systems, in interaction with glucocorticoids, modulate affect and cognition and suppress behaviors that are inadequate for the situation. Increased noradrenergic activity in the brain stem increases vigilance and alertness. These acute stress responses represent adaptive mechanisms that are critical to survival of the species (33). Considered from this perspective, it would not be adaptive to be fatigued or lack energy during periods of threat. Indeed, several components of the acute stress response appear to counteract fatigue directly and reverse the established features of CFS. For example, there is evidence that the pathophysiology of CFS involves dysregulation of glucocorticoid signaling and consequently lack of control of immune mediators, such as cytokines, which are thought to cause fatigue (28,34). Sustained activation of the stress responses, elicited by the events of September 11, 2001, and the threats experienced thereafter, might have overridden a state of deficient glucocorticoid signaling in fatigued people and might have counteracted a fatigue-like symptom complex, leading toward lower prevalence estimates of fatiguing symptoms in the time after the attacks. With chronic or repeated stress, or after cessation of the threat, such psychobiological adaptations might evolve into an exhausted system and relapse of fatigue.
Because the present study did not collect data on potential psychological or biological mechanisms, it is impossible to decide which of the mechanisms might be most plausible. In addition, the design of our study does not allow for direct inference that the change in prevalence rates was because of the terrorist attacks. Our findings might suggest that there are complex relationships between stress or trauma and fatiguing illnesses, but this assumption needs to be verified in future studies using a personalized approach. In such studies, it must be considered that timing, duration, and other characteristics of stressful life experiences and interactions with other risk factors might be important effect modifiers. We suggest that epidemiological and clinical studies specifically designed to evaluate the relationship between different types of stresses and fatiguing illnesses are needed. Such studies should include measures on psychobiological pathways by which stresses across the lifespan, in interaction with other factors, may alter physiological systems implicated in the pathogenesis of fatiguing illnesses. Identifying the psychobiological and developmental pathways to individual resilience or vulnerability for fatiguing illnesses will considerably advance the understanding of the pathogenesis of these illnesses and may enable the development of diagnostic markers of vulnerability and the implementation of preventive strategies that directly target these pathways in populations at risk.
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
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NOTES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
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Received for publication January 22, 2004.
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