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Cumulative life stress in chronic fatigue syndrome
Psychiatry Research 189 (2011) 318–320
Contents lists available at ScienceDirect
Psychiatry Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p s yc h r e s
Brief report
Cumulative life stress in chronic fatigue syndrome Urs M. Nater a, b, Elizabeth Maloney a, Christine Heim c, William C. Reeves a, d,⁎ a
Chronic Viral Diseases Branch, Division of High-Consequence Pathogens and Pathology (proposed), National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control & Prevention, Atlanta, GA, USA b Clinical Biopsychology, Dept. of Psychology, University of Marburg, Germany c Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA d Current affiliation: Public Health Surveillance Program Office, Office of Surveillance, Epidemiology and Laboratory Services, Centers for Disease Control & Prevention, Atlanta, GA, USA
a r t i c l e
i n f o
Article history: Received 2 September 2010 Received in revised form 18 May 2011 Accepted 6 July 2011 Keywords: Stress Life events Chronic fatigue syndrome
a b s t r a c t We studied the impact of cumulative life stress on CFS in a population-based study. We found that exposure to stressors was significantly more common in persons with CFS compared to NF controls; those with CFS reported experiencing significantly higher levels of psychological distress. Also, post-traumatic stress disorder was significantly more common in people with CFS. These results not only corroborate findings from other studies but, importantly, extend those by: a) measuring a comprehensive spectrum of stress variables, b) for the first time presenting data on stress in a population-based study, thus minimizing the effects of recruitment bias, and c) diagnosing CFS by means of standardized, validated scales, thus allowing replication and extension of our findings. Stress may be an important factor in the pathophysiology of CFS. Consequently, future studies should provide a more detailed understanding of the processes that lead from stress to CFS using longitudinal designs. Published by Elsevier Ireland Ltd.
1. Introduction Chronic fatigue syndrome (CFS) affects about 0.1–2.5% of the general adult population (Reeves et al., 2007). There are no characteristic clinical signs or laboratory abnormalities so CFS must be diagnosed by self-reported symptoms and ruling-out medical and psychiatric conditions with similar clinical presentations (Fukuda et al., 1994). Because the pathophysiology remains inchoate (Prins et al., 2006), current treatment modalities seek to alleviate symptoms. Critically, given the magnitude of the public health problem, no primary or secondary prevention strategies have yet been designed or tested. However, stress has been increasingly recognized as important in both the etiology and pathophysiology of CFS (Nater et al., 2010). Various studies reported that persons with CFS experienced significantly more stressful life events in the year before illness onset than controls during the same calendar time-period (Reyes et al., 1996; Masuda et al., 2002; Faulkner and Smith, 2008). Very few studies focused on qualitative measures of experienced or perceived stress levels. One study found that the physical symptoms of CFS were exacerbated in people who experienced Hurricane Andrew (Lutgendorf et al., 1995). Another study found that about 15% of persons with CFS had posttraumatic stress disorder (PTSD), which reflects aberrant response to extreme stress (Nater et al., 2009).
Thus, both occurrence of recent stressful life events and chronic stress levels appear to be increased in individuals with CFS, but most studies have operationalized stress by quantitatively counting life events. Stress research has repeatedly shown that the qualitative evaluation of a life event as negative is crucial in its subsequent effect on health and no studies of which we are aware have measured stress perception, occurrence of stressful life events and stress levels within the same study. In addition, published studies have defined CFS by different criteria and with varying degrees of rigor. Finally, almost all published studies include persons with CFS enrolled from primary or tertiary care centres which may result in self-selection bias; only 50% of people with CFS have consulted a physician for their illness and fewer than 20% have been appropriately diagnosed (Solomon and Reeves, 2004). The objectives of the current study were therefore to assess the occurrence of quantitative and qualitative measures of stress in a population-based sample of CFS, and examine the strength of the association of different aspects of stress with CFS. 2. Methods This study adhered to U.S. Department of Health and Human Services human experimentation guidelines and received Institutional Review Board approval from the CDC and collaborating institutions. All participants gave informed consent. 2.1. Study design
⁎ Corresponding author at: Public Health Surveillance Program Office, Mail Stop E-97, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333, USA. E-mail address: [email protected] (W.C. Reeves). 0165-1781/$ – see front matter. Published by Elsevier Ireland Ltd. doi:10.1016/j.psychres.2011.07.015
This study enrolled participants from the Wichita CFS Surveillance Study, conducted between 1997 and 2000 (for more information, please refer to Reyes et al., 2003) who also participated in a 2-day in-hospital case control study (conducted
U.M. Nater et al. / Psychiatry Research 189 (2011) 318–320 between 2002 and 2003). In brief, 43 subjects meeting criteria for CFS and 60 nonfatigued (NF) subjects were identified. CFS was diagnosed by criteria of the 1994 International Research Case Definition (Fukuda et al., 1994) as recommended by the International CFS study group (Reeves et al., 2003). To identify exclusionary medical conditions, a standardized medical history, review of current medications, standardized physical examination as well as routine blood and urine laboratory tests were performed as recommended by the International CFS Study Group. 2.2. Measurements Psychometric instruments were self-administered during the in-hospital study. We used the Traumatic Life Events Questionnaire (TLEQ) (Kubany et al., 2000) to measure life events that most people consider to be traumatic. The TLEQ is used to assess exposure to 21 types of potentially traumatic events ranging incrementally from those which are not highly personal stressors (e.g., natural disasters, motor vehicle accidents) to personally sensitive events (e.g., intimate partner abuse, sexual abuse). The TLEQ records frequency of occurrence of each trauma and the TLEQ score reflects the total number of traumatic events. We used the Life Experiences Survey (LES) (Sarason et al., 1978) to measure severe major life events not considered to be traumatic which occurred in the past year. Subjects rate the desirability and impact of events which they have experienced in the last 12 months (divided into two 6-months intervals). Subjects in the present study completed 47 items and three blank spaces in the first section of the LES. We computed a positive LES change score by summing the impact ratings of events which subjects designated as positive and computed a negative change score by summing the impact ratings of events designated as negative. We used the Perceived Stress Scale (PSS) (Cohen et al., 1983) to measure perceived levels of stress. The PSS contains 14 items and is used to assess how unpredictable, uncontrollable, and overloaded respondents considered their lives to be, using the last week as a reference time frame. We computed a summary score (ranging from 0 to 40) for each participant. We used the Diagnostic Interview Schedule (DIS) (Robins et al., 1995) to identify a current diagnosis of PTSD according to DSM-IV, and used the Davidson Trauma Scale (DTS) (Davidson et al., 1997) to measure PTSD symptoms on a dimensional level. The DTS is a self-report questionnaire used to record the frequency and severity of PTSD symptoms. Davidson proposed that a threshold of 40 for a total symptom score was highly likely to lead to a diagnosis of PTSD. 2.3. Statistical analyses We used the chi-square test to compare the distributions of sex and race (white, non-white) and Fisher's exact test for comparisons with cell numbers lower than 5 between the groups of CFS cases and NF controls; and used the t-test to compare mean ages between these two study groups. We utilized analysis of variance to compare mean levels of stress measurements adjusting for age (continuous), sex, and race (white, non-white). Logistic regression was performed to examine the association between CFS (dependent variable) and stress variables, adjusting for age (continuous), sex, and race (white, non-white). For all analyses, SPSS 19.00 was used. All tests of significance were two-tailed with the alpha level set at 0.05.
3. Results CFS cases were on average 50 years of age and were predominantly white women (CFS mean age: 50.6 years, 36 women, seven men, 40 white, three non-white; NF mean age: 50.5 years, 48 women, 12 men, 56 white, four non-white). Persons with CFS and non-fatigued (NF) controls differed significantly with respect to mean scores measuring traumatic life events, major life events, especially major life events perceived as having a negative impact, perceived stress in the previous week and the Davidson Trauma Summary (DTS) score (Table 1), after controlling for age, sex, and race. In each comparison, persons with CFS had higher mean scores, indicating a higher number of traumatic life events, total major life events (and specifically major negative live events), perceived stress and DTS score. Further, using a possible PTSD diagnosis based on a DTS score N40, significantly more persons with PTSD were detected among the CFS group compared to controls. However, when PTSD diagnosis was ascertained using the DIS, fewer subjects were classified as having PTSD, and the differences between the CFS and NF groups were no longer significant. Finally, a multivariate logistic regression analysis was conducted to determine which of the stress sub-scales found to be significant in the prior analyses remained as significant independent predictors of CFS, controlling for age, sex, and race. This analysis indicated that the
319
Table 1 Stress scores in cases with chronic fatigue syndrome (CFS) and non-fatigued controls (NF). Stress measurement instruments Traumatic Life Events Scores Mean Number of Discrete Events (S.D.) Life Events Scores Mean Positive Change Score (S.D.) Mean Negative Change Score (S.D.) Perceived Stress Score Mean score (S.D.) Davidson Trauma Score Mean score (S.D.) PTSD—as measured by: Davidson Trauma Scale Yes (%)/No Diagnostic Interview Schedule Yes (%)/No
CFS (n = 43)
NF (n = 60)
Statistics (df)
P
15.1 (12.2)
8.1 (8.2)
F = 12.21 (1/98)
0.001
4.1 (5.0)
4.7 (5.9)
0.506
− 9.8 (12.9)
− 3.5 (5.4)
F = 0.45 (1/94) F = 11.12 (1/98)
16.9 (6.6)
8.0 (4.2)
F = 67.81 (1/98)
b 0.001
28.3 (22.6)
5.4 (6.3)
F = 49.61 (1/91)
b 0.001
11 (26.8%)/30
0/55
b 0.001
4 (9.3%)/39
1 (1.7%)/59
0.158
0.001
All P values for mean comparisons are controlled for age, sex, race. Traumatic Life Events Questionnaire (TLEQ) was used to measure traumatic life events; Life Experiences Survey (LES) was used to measure the life events score; Perceived Stress Scale (PSS) was used to measure the perceived stress score; Davidson Trauma Scale (DTS) was used to measure the Davidson trauma score; DTS N 40 was used to determine PTSD based on the DTS; Diagnostic Interview Schedule (DIS) was used to measure PTSD; S.D.: standard deviation.
perceived stress summary score (P = 0.042; odds ratio, OR: 1.18; confidence interval, CI: 1.01–1.39) and Davidson trauma summary score (P = 0.033; odds ratio, OR: 1.09; confidence interval, CI: 1.01– 1.18) were significantly associated with CFS, but the other stress variables were not (classification hit/miss rate was 73.2% for CFS and 87.3% for NF). 4. Discussion Exposure to stressors was significantly more common in persons with CFS compared to NF controls; those with CFS reported experiencing significantly higher levels of psychological distress; and, PTSD was significantly more common in people with CFS. These results corroborate findings from other studies and, importantly, extend those by: a) measuring a comprehensive spectrum of stress variables, b) for the first time presenting data on stress in a population-based study, thus minimizing the effects of recruitment bias; c) diagnosing CFS by means of standardized, validated scales, thus allowing replication and extension of our findings. In effect, we showed that the number of reported life events per se (as measured by the TLEQ) is not significantly associated with CFS, but significant associations between CFS and stress reports reflect the subjective experience of stress levels, as manifested by increased unpredictability, uncontrollability, and experienced overload; in addition, typical symptoms of PTSD (e.g., high arousal and stress-related intrusive thoughts) were strongly and significantly associated with CFS. We have previously shown that stress experienced early in life magnifies the risk of developing CFS later in life (Heim et al., 2006). In the current study, we focused on cumulative and current life stress and found this to be an additional important factor. Due to the crosssectional nature of this and other examinations, the question remains whether life events and experience of stress might actually be triggering CFS or whether these variables occur more often as a consequence of the illness. Childhood adversity as a risk factor of CFS is associated with changes in stress regulatory systems (Heim et al., 2006, 2009). Upon
320
U.M. Nater et al. / Psychiatry Research 189 (2011) 318–320
additional challenge, e.g. exposure to a stimulus that is experienced as stressful, neuroendocrine alterations might lead to disinhibition of central nervous and peripheral immune and autonomic responses (see e.g. Heim et al., 2009), and ultimately evolve into the characteristic symptom pattern of CFS. Thus, it might be suggested that CFS may be a disorder of adaptation and failure to compensate in response to psychological challenge. Numerous treatments have been applied to CFS patients with various results. Experimental data support efficacy of graded exercise training and cognitive behavioral therapy (CBT) (Rimes and Chalder, 2005). CBT strategies for CFS typically involve organizing activity and rest cycles, initiating graded increases in activity, establishing a consistent sleep regimen, attempting to restructure beliefs around self, as well as disease attributions, and stress management. The latter employs stress reducing strategies and improves coping behavior. It seems critical to devote research resources to a detailed understanding of the processes that lead from stress to CFS in order to improve current treatment strategies. Conflict of interest statement The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agency. Acknowledgments This research was supported in part by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and CDC (UMN). The authors acknowledge the expertise of Abt Associates in managing the study. UMN acknowledges funding by the Volkswagen Foundation.
References Cohen, S., Kamarck, T., Mermelstein, R., 1983. A global measure of perceived stress. Journal of Health and Social Behavior 24 (4), 385–396. Davidson, J.R., Book, S.W., Colket, J.T., Tupler, L.A., Roth, S., David, D., Hertzberg, M., Mellman, T., Beckham, J.C., Smith, R.D., Davison, R.M., Katz, R., Feldman, M.E., 1997. Assessment of a new self-rating scale for post-traumatic stress disorder. Psychological Medicine 27 (1), 153–160. Faulkner, S., Smith, A., 2008. A longitudinal study of the relationship between psychological distress and recurrence of upper respiratory tract infections in chronic fatigue syndrome. British Journal of Health Psychology 13, 177–186.
Fukuda, K., Straus, S.E., Hickie, I., Sharpe, M.C., Dobbins, J.G., Komaroff, A., 1994. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Annals of Internal Medicine 121 (12), 953–959. Heim, C., Wagner, D., Maloney, E., Papanicolaou, D.A., Solomon, L., Jones, J.F., Unger, E.R., Reeves, W.C., 2006. Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study. Archives of General Psychiatry 63 (11), 1258–1266. Heim, C., Nater, U.M., Maloney, E., Boneva, R., Jones, J.F., Reeves, W.C., 2009. Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction. Archives of General Psychiatry 66 (1), 72–80. Kubany, E.S., Haynes, S.N., Leisen, M.B., Owens, J.A., Kaplan, A.S., Watson, S.B., Burns, K., 2000. Development and preliminary validation of a brief broad-spectrum measure of trauma exposure: the Traumatic Life Events Questionnaire. Psychological Assessment 12 (2), 210–224. Lutgendorf, S.K., Antoni, M.H., Ironson, G., Fletcher, M.A., Penedo, F., Baum, A., Schneiderman, N., Klimas, N., 1995. Physical symptoms of chronic fatigue syndrome are exacerbated by the stress of Hurricane Andrew. Psychosomatic Medicine 57 (4), 310–323. Masuda, A., Munemoto, T., Yamanaka, T., Takei, M., Tei, C., 2002. Psychosocial characteristics and immunological functions in patients with postinfectious chronic fatigue syndrome and noninfectious chronic fatigue syndrome. Journal of Behavioral Medicine 25 (5), 477–485. Nater, U.M., Lin, J.-M., Maloney, E., Jones, J.F., Tian, H., Raison, C.L., Reeves, W.C., Heim, C., 2009. Psychiatric comorbidity in persons with chronic fatigue syndrome in the general population of Georgia. Psychosomatic Medicine 71 (5), 557–565. Nater, U.M., Heim, C., Reeves, W.C., 2010. The role of stress in chronic fatigue syndrome. International Journal of Medical and Biological Frontiers 16 (7/8), 869–884. Prins, J.B., van der Meer, J.W., Bleijenberg, G., 2006. Chronic fatigue syndrome. Lancet 367 (9507), 346–355. Reeves, W.C., Lloyd, A., Vernon, S.D., Klimas, N., Jason, L.A., Bleijenberg, G., Evengard, B., White, P.D., Nisenbaum, R., Unger, E.R., 2003. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Services Research 3 (1), 25. Reeves, W.C., Jones, J.F., Maloney, E., Heim, C., Hoaglin, D.C., Boneva, R.S., Morrissey, M., Devlin, R., 2007. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Population Health Metrics 5, 5. Reyes, M., Dobbins, J.G., Mawle, A.C., Steele, L., Gary Jr., H.E., Malani, H., Schmid, S., Fukuda, K., Stewart, J., Nisenbaum, R., Reeves, W.C., 1996. Risk factors for CFS: a case control study. Journal of Chronic Fatigue Syndrome 2, 17–33. Reyes, M., Nisenbaum, R., Hoaglin, D.C., Unger, E.R., Emmons, C., Randall, B., Stewart, J. A., Abbey, S., Jones, J.F., Gantz, N., Minden, S., Reeves, W.C., 2003. Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Archives of Internal Medicine 163 (13), 1530–1536. Rimes, K.A., Chalder, T., 2005. Treatments for chronic fatigue syndrome. Occupational Medicine (London) 55 (1), 32–39. Robins, L., Cottler, L., Bucholz, K., Compton, W., 1995. Diagnostic Interview Schedule for DSM-IV (DIS-IV). Washington University, St. Louis, MO. Sarason, I.G., Johnson, J.H., Siegel, J.M., 1978. Assessing the impact of life changes: development of the Life Experiences Survey. Journal of Consulting and Clinical Psychology 46 (5), 932–946. Solomon, L., Reeves, W.C., 2004. Factors influencing the diagnosis of chronic fatigue syndrome. Archives of Internal Medicine 164 (20), 2241–2245.
Contents lists available at ScienceDirect
Psychiatry Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p s yc h r e s
Brief report
Cumulative life stress in chronic fatigue syndrome Urs M. Nater a, b, Elizabeth Maloney a, Christine Heim c, William C. Reeves a, d,⁎ a
Chronic Viral Diseases Branch, Division of High-Consequence Pathogens and Pathology (proposed), National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control & Prevention, Atlanta, GA, USA b Clinical Biopsychology, Dept. of Psychology, University of Marburg, Germany c Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA d Current affiliation: Public Health Surveillance Program Office, Office of Surveillance, Epidemiology and Laboratory Services, Centers for Disease Control & Prevention, Atlanta, GA, USA
a r t i c l e
i n f o
Article history: Received 2 September 2010 Received in revised form 18 May 2011 Accepted 6 July 2011 Keywords: Stress Life events Chronic fatigue syndrome
a b s t r a c t We studied the impact of cumulative life stress on CFS in a population-based study. We found that exposure to stressors was significantly more common in persons with CFS compared to NF controls; those with CFS reported experiencing significantly higher levels of psychological distress. Also, post-traumatic stress disorder was significantly more common in people with CFS. These results not only corroborate findings from other studies but, importantly, extend those by: a) measuring a comprehensive spectrum of stress variables, b) for the first time presenting data on stress in a population-based study, thus minimizing the effects of recruitment bias, and c) diagnosing CFS by means of standardized, validated scales, thus allowing replication and extension of our findings. Stress may be an important factor in the pathophysiology of CFS. Consequently, future studies should provide a more detailed understanding of the processes that lead from stress to CFS using longitudinal designs. Published by Elsevier Ireland Ltd.
1. Introduction Chronic fatigue syndrome (CFS) affects about 0.1–2.5% of the general adult population (Reeves et al., 2007). There are no characteristic clinical signs or laboratory abnormalities so CFS must be diagnosed by self-reported symptoms and ruling-out medical and psychiatric conditions with similar clinical presentations (Fukuda et al., 1994). Because the pathophysiology remains inchoate (Prins et al., 2006), current treatment modalities seek to alleviate symptoms. Critically, given the magnitude of the public health problem, no primary or secondary prevention strategies have yet been designed or tested. However, stress has been increasingly recognized as important in both the etiology and pathophysiology of CFS (Nater et al., 2010). Various studies reported that persons with CFS experienced significantly more stressful life events in the year before illness onset than controls during the same calendar time-period (Reyes et al., 1996; Masuda et al., 2002; Faulkner and Smith, 2008). Very few studies focused on qualitative measures of experienced or perceived stress levels. One study found that the physical symptoms of CFS were exacerbated in people who experienced Hurricane Andrew (Lutgendorf et al., 1995). Another study found that about 15% of persons with CFS had posttraumatic stress disorder (PTSD), which reflects aberrant response to extreme stress (Nater et al., 2009).
Thus, both occurrence of recent stressful life events and chronic stress levels appear to be increased in individuals with CFS, but most studies have operationalized stress by quantitatively counting life events. Stress research has repeatedly shown that the qualitative evaluation of a life event as negative is crucial in its subsequent effect on health and no studies of which we are aware have measured stress perception, occurrence of stressful life events and stress levels within the same study. In addition, published studies have defined CFS by different criteria and with varying degrees of rigor. Finally, almost all published studies include persons with CFS enrolled from primary or tertiary care centres which may result in self-selection bias; only 50% of people with CFS have consulted a physician for their illness and fewer than 20% have been appropriately diagnosed (Solomon and Reeves, 2004). The objectives of the current study were therefore to assess the occurrence of quantitative and qualitative measures of stress in a population-based sample of CFS, and examine the strength of the association of different aspects of stress with CFS. 2. Methods This study adhered to U.S. Department of Health and Human Services human experimentation guidelines and received Institutional Review Board approval from the CDC and collaborating institutions. All participants gave informed consent. 2.1. Study design
⁎ Corresponding author at: Public Health Surveillance Program Office, Mail Stop E-97, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333, USA. E-mail address: [email protected] (W.C. Reeves). 0165-1781/$ – see front matter. Published by Elsevier Ireland Ltd. doi:10.1016/j.psychres.2011.07.015
This study enrolled participants from the Wichita CFS Surveillance Study, conducted between 1997 and 2000 (for more information, please refer to Reyes et al., 2003) who also participated in a 2-day in-hospital case control study (conducted
U.M. Nater et al. / Psychiatry Research 189 (2011) 318–320 between 2002 and 2003). In brief, 43 subjects meeting criteria for CFS and 60 nonfatigued (NF) subjects were identified. CFS was diagnosed by criteria of the 1994 International Research Case Definition (Fukuda et al., 1994) as recommended by the International CFS study group (Reeves et al., 2003). To identify exclusionary medical conditions, a standardized medical history, review of current medications, standardized physical examination as well as routine blood and urine laboratory tests were performed as recommended by the International CFS Study Group. 2.2. Measurements Psychometric instruments were self-administered during the in-hospital study. We used the Traumatic Life Events Questionnaire (TLEQ) (Kubany et al., 2000) to measure life events that most people consider to be traumatic. The TLEQ is used to assess exposure to 21 types of potentially traumatic events ranging incrementally from those which are not highly personal stressors (e.g., natural disasters, motor vehicle accidents) to personally sensitive events (e.g., intimate partner abuse, sexual abuse). The TLEQ records frequency of occurrence of each trauma and the TLEQ score reflects the total number of traumatic events. We used the Life Experiences Survey (LES) (Sarason et al., 1978) to measure severe major life events not considered to be traumatic which occurred in the past year. Subjects rate the desirability and impact of events which they have experienced in the last 12 months (divided into two 6-months intervals). Subjects in the present study completed 47 items and three blank spaces in the first section of the LES. We computed a positive LES change score by summing the impact ratings of events which subjects designated as positive and computed a negative change score by summing the impact ratings of events designated as negative. We used the Perceived Stress Scale (PSS) (Cohen et al., 1983) to measure perceived levels of stress. The PSS contains 14 items and is used to assess how unpredictable, uncontrollable, and overloaded respondents considered their lives to be, using the last week as a reference time frame. We computed a summary score (ranging from 0 to 40) for each participant. We used the Diagnostic Interview Schedule (DIS) (Robins et al., 1995) to identify a current diagnosis of PTSD according to DSM-IV, and used the Davidson Trauma Scale (DTS) (Davidson et al., 1997) to measure PTSD symptoms on a dimensional level. The DTS is a self-report questionnaire used to record the frequency and severity of PTSD symptoms. Davidson proposed that a threshold of 40 for a total symptom score was highly likely to lead to a diagnosis of PTSD. 2.3. Statistical analyses We used the chi-square test to compare the distributions of sex and race (white, non-white) and Fisher's exact test for comparisons with cell numbers lower than 5 between the groups of CFS cases and NF controls; and used the t-test to compare mean ages between these two study groups. We utilized analysis of variance to compare mean levels of stress measurements adjusting for age (continuous), sex, and race (white, non-white). Logistic regression was performed to examine the association between CFS (dependent variable) and stress variables, adjusting for age (continuous), sex, and race (white, non-white). For all analyses, SPSS 19.00 was used. All tests of significance were two-tailed with the alpha level set at 0.05.
3. Results CFS cases were on average 50 years of age and were predominantly white women (CFS mean age: 50.6 years, 36 women, seven men, 40 white, three non-white; NF mean age: 50.5 years, 48 women, 12 men, 56 white, four non-white). Persons with CFS and non-fatigued (NF) controls differed significantly with respect to mean scores measuring traumatic life events, major life events, especially major life events perceived as having a negative impact, perceived stress in the previous week and the Davidson Trauma Summary (DTS) score (Table 1), after controlling for age, sex, and race. In each comparison, persons with CFS had higher mean scores, indicating a higher number of traumatic life events, total major life events (and specifically major negative live events), perceived stress and DTS score. Further, using a possible PTSD diagnosis based on a DTS score N40, significantly more persons with PTSD were detected among the CFS group compared to controls. However, when PTSD diagnosis was ascertained using the DIS, fewer subjects were classified as having PTSD, and the differences between the CFS and NF groups were no longer significant. Finally, a multivariate logistic regression analysis was conducted to determine which of the stress sub-scales found to be significant in the prior analyses remained as significant independent predictors of CFS, controlling for age, sex, and race. This analysis indicated that the
319
Table 1 Stress scores in cases with chronic fatigue syndrome (CFS) and non-fatigued controls (NF). Stress measurement instruments Traumatic Life Events Scores Mean Number of Discrete Events (S.D.) Life Events Scores Mean Positive Change Score (S.D.) Mean Negative Change Score (S.D.) Perceived Stress Score Mean score (S.D.) Davidson Trauma Score Mean score (S.D.) PTSD—as measured by: Davidson Trauma Scale Yes (%)/No Diagnostic Interview Schedule Yes (%)/No
CFS (n = 43)
NF (n = 60)
Statistics (df)
P
15.1 (12.2)
8.1 (8.2)
F = 12.21 (1/98)
0.001
4.1 (5.0)
4.7 (5.9)
0.506
− 9.8 (12.9)
− 3.5 (5.4)
F = 0.45 (1/94) F = 11.12 (1/98)
16.9 (6.6)
8.0 (4.2)
F = 67.81 (1/98)
b 0.001
28.3 (22.6)
5.4 (6.3)
F = 49.61 (1/91)
b 0.001
11 (26.8%)/30
0/55
b 0.001
4 (9.3%)/39
1 (1.7%)/59
0.158
0.001
All P values for mean comparisons are controlled for age, sex, race. Traumatic Life Events Questionnaire (TLEQ) was used to measure traumatic life events; Life Experiences Survey (LES) was used to measure the life events score; Perceived Stress Scale (PSS) was used to measure the perceived stress score; Davidson Trauma Scale (DTS) was used to measure the Davidson trauma score; DTS N 40 was used to determine PTSD based on the DTS; Diagnostic Interview Schedule (DIS) was used to measure PTSD; S.D.: standard deviation.
perceived stress summary score (P = 0.042; odds ratio, OR: 1.18; confidence interval, CI: 1.01–1.39) and Davidson trauma summary score (P = 0.033; odds ratio, OR: 1.09; confidence interval, CI: 1.01– 1.18) were significantly associated with CFS, but the other stress variables were not (classification hit/miss rate was 73.2% for CFS and 87.3% for NF). 4. Discussion Exposure to stressors was significantly more common in persons with CFS compared to NF controls; those with CFS reported experiencing significantly higher levels of psychological distress; and, PTSD was significantly more common in people with CFS. These results corroborate findings from other studies and, importantly, extend those by: a) measuring a comprehensive spectrum of stress variables, b) for the first time presenting data on stress in a population-based study, thus minimizing the effects of recruitment bias; c) diagnosing CFS by means of standardized, validated scales, thus allowing replication and extension of our findings. In effect, we showed that the number of reported life events per se (as measured by the TLEQ) is not significantly associated with CFS, but significant associations between CFS and stress reports reflect the subjective experience of stress levels, as manifested by increased unpredictability, uncontrollability, and experienced overload; in addition, typical symptoms of PTSD (e.g., high arousal and stress-related intrusive thoughts) were strongly and significantly associated with CFS. We have previously shown that stress experienced early in life magnifies the risk of developing CFS later in life (Heim et al., 2006). In the current study, we focused on cumulative and current life stress and found this to be an additional important factor. Due to the crosssectional nature of this and other examinations, the question remains whether life events and experience of stress might actually be triggering CFS or whether these variables occur more often as a consequence of the illness. Childhood adversity as a risk factor of CFS is associated with changes in stress regulatory systems (Heim et al., 2006, 2009). Upon
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additional challenge, e.g. exposure to a stimulus that is experienced as stressful, neuroendocrine alterations might lead to disinhibition of central nervous and peripheral immune and autonomic responses (see e.g. Heim et al., 2009), and ultimately evolve into the characteristic symptom pattern of CFS. Thus, it might be suggested that CFS may be a disorder of adaptation and failure to compensate in response to psychological challenge. Numerous treatments have been applied to CFS patients with various results. Experimental data support efficacy of graded exercise training and cognitive behavioral therapy (CBT) (Rimes and Chalder, 2005). CBT strategies for CFS typically involve organizing activity and rest cycles, initiating graded increases in activity, establishing a consistent sleep regimen, attempting to restructure beliefs around self, as well as disease attributions, and stress management. The latter employs stress reducing strategies and improves coping behavior. It seems critical to devote research resources to a detailed understanding of the processes that lead from stress to CFS in order to improve current treatment strategies. Conflict of interest statement The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agency. Acknowledgments This research was supported in part by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and CDC (UMN). The authors acknowledge the expertise of Abt Associates in managing the study. UMN acknowledges funding by the Volkswagen Foundation.
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