Perceived Stress, Illness Uncertainty, and Disease Symptomatology in Multiple Sclerosis
Matthew R. Sorenson, PhD, RN; Linda Janusek, PhD, RN; and Herbert L. Mathews, PhD
Abstract
This study examined the relationships among illness uncertainty, perceived stress and disease symptomatology in outpatients with multiple sclerosis (MS). Forty three subjects with MS and 38 healthy control subjects completed a series of standardized psychological instruments. MS subjects also completed a measure of disease symptomatology. MS subjects scored significantly higher on measures of perceived stress and negative mood, with a significant reduction in positive affect when compared with control subjects. Also, these measures of perceived stress, negative mood, and illness uncertainty correlated significantly with disease symptomatology. Additional analysis demonstrated that perceived stress had direct effects on MS symptomatology, with indirect effects for illness uncertainty. Perceived stress and illness uncertainty may contribute to the occurrence of disease symptoms in individuals with MS.
Key Words: perceived stress, multiple sclerosis, illness uncertainty, symptomatology.
Background of the Problem
Multiple sclerosis (MS) is a chronic, degenerative neurologic disorder evolving from progressive destruction of the myelin sheath, with a resulting loss of nerve propagation. The destruction of myelin is believed to occur as result of an immune response in which immune components attack myelin in the central nervous system (Boccaccio & Steinman, 1996). While the pathogenic process of MS is not fully understood, MS is believed to be an immunopathologic disorder which may emerge from the interaction of genetic susceptibility with precipitating environmental factors (Dean, 1994; Kurtzke, 1993; Weinshenker, 1996). While controversial, one such precipitating factor may be a state of psychological stress that could contribute to the exacerbation of MS through immune modulation (van Noort, 1996).
Illness Uncertainty
The existence of a state of illness uncertainty may contribute to the development of increased levels of psychological stress. Illness uncertainty has been defined as the inability to successfully ascribe meaning to illness-related events (Mishel & Braden, 1988). The lack of meaning is conceptualized to adversely affect cognitive appraisal of illness-related events, contributing to an interpretation of illness-related events with unclear meaning as a potential threat. The existence of a threat appraisal can then lead to the emergence of a state of perceived stress (Lazarus & Folkman, 1984; Mishel, 1981). In hospitalized medical patients, illness uncertainty has been demonstrated to predict the level of perceived stress (Mishel, 1984).
The individual with MS may experience substantial uncertainty regarding disease progression due to the unpredictable course of the disease (Kroencke & Denney, 1999; Zedlow & Pavlou, 1984). The level of such uncertainty that surrounds a chronic disease can then pose a threat to the individual and serve to induce stress (Mishel, 1981, 1984). The illness-related uncertainty of MS and the corresponding deterioration in functional ability could increase an individual’s level of perceived stress and induce negative mood states. In one study, the presence of illness uncertainty was found to account for a significant degree of mood state variance (Wineman, Schwetz, Goodkin, & Rudick, 1996). The emotional well-being of individuals with MS could then be influenced by “a set of stress/uncertainty variables” (Wineman et al., 1996). Those with MS that perceived the illness as having a highly uncertain course, and appraised living with disability as a potential threat, have been shown to experience greater disruption of emotional well-being (Wineman, Durand, & Steiner, 1994).
Illness-related uncertainty could then be a potential contributing factor to a heightened level of psychological stress. Such a state of psychological stress may contribute to disease exacerbation if not actual disease onset. Prior to the onset of symptoms, the individual with MS may report a higher incidence of psychological stress (Grant et al., 1989; Warren, Greenhill, & Warren, 1982; Warren, Warren, & Cockerill, 1991). The presence of psychological stress has also been shown to contribute to disease exacerbation (Warren et al., 1991). Questions remain, however, as to whether stress functions as a causative agent in exacerbation, or whether the occurrence of disease exacerbation itself, produces a higher degree of perceived stress (LaRocca, 1984; Warren, 1990; Warren et al., 1982; Warren et al., 1991). It could be speculated that illness uncertainty may have a direct relationship with disease symptoms, one independent of its relationship with psychological stress. While illness uncertainty has been demonstrated associated with levels of psychological distress in individuals with MS (Mullins et al., 2001; Wineman, O’Brien, Nealon, & Kaskel, 1993; Wineman et al., 1996), the link between illness uncertainty and reported disease symptomatology is as yet unclear.
Purpose of the Study
The purpose of the present study was to examine the relationships among illness uncertainty, perceived stress, and disease symptomatology in MS and control subjects, in order to determine if perceived stress and illness uncertainty related to level of disease symptomatology in individuals with MS. MS subjects were recruited from outpatient settings, in order to examine the relationship between stress and disease in the daily life of MS subjects, rather than examining individuals hospitalized for disease exacerbation. It was hypothesized that MS subjects would exhibit higher levels of perceived stress than control subjects. In addition, it was hypothesized that illness uncertainty would significantly correlate with perceived stress and, secondly, that increased levels of psychological stress and illness uncertainty would significantly correlate with disease symptomatology.
Method
Participants
A convenience sample of male and female patients previously diagnosed with clinically definite MS using the Poser criteria was recruited from the outpatient neurology clinic of a large Mid-Western Level I Medical Center located in Illinois and from surrounding regional community support groups. Control subjects were recruited from the community at large. Prior to implementation of the study, approval was obtained from the Institutional Review Board (IRB).
Subjects were asked to complete a series of standardized psychological instruments that assessed self-reported levels of: perceived stress, illness-related uncertainty, and mood state. Control subjects completed three self-report measures and one demographic data form. MS study participants completed four self-report measures and one demographic data form. The self-report measures completed by MS subjects were: the Perceived Stress Scale (PSS), the Mishel Uncertainty in Illness Scale–Community Version (MUIS), the Profile of Mood States (POMS) and the MS-Related Symptom Checklist (MSSC). Control subjects did not complete the MUIS or the MSSC.
Measures
The Perceived Stress Scale (PSS) is a 10-item, subjective self-report measure designed to measure the cognitive appraisal of a global state of stress (Cohen, 1994). Homogeneity reliability has been demonstrated through a Cronbach’s alpha coefficient of .75 in a norm-referenced sample (Cohen & Williamson, 1988). In this study homogeneity reliability as determined by Cronbach’s alpha was .91.
The Mishel Uncertainty in Illness Scale (MUIS) is a 28-item measure using a five-point Likert type scale, designed to measure illness uncertainty (Mishel, 1981). The version of the MUIS used in this study is derived from the full, 28-item measure designed for use with individuals currently not hospitalized. Reliability for this 23-item version of the MUIS has been shown to range from .74 to .92 (Mishel, 1997). In this study, the Cronbach’s alpha score was .86.
The Profile of Mood States (POMS) is a 65-item, self-report measure designed to assess affect and mood (McNair, Lorr, & Droppleman, 1992). A total mood disturbance score can be derived (POMS-TD). Additionally, six subscales assess further components of mood: tension-anxiety (POMS-T), depression-dejection (POMS-D), anger-hostility (POMS-A), vigor-activity (POMS-V), fatigue-inertia (POMS-F), and confusion-bewilderment (POMS-C) (McNair et al.). All subscales assess for the presence of negative emotionality and mood except for the vigor-activity subscale. The vigor-activity subscale has been identified as a measure of positive affect (McNair et al.). Homogeneity reliability was demonstrated through Kuder-Richardson 20 scores of between .84 and .95 for the six factors (McNair et al.). For this study, Cronbach’s alpha subscale scores ranged from .69 to .96.
The MS-Related Symptom Checklist (MSSC) is a 26-item, self-report measure designed to assess for the presence of 26 disease symptoms common in patients with MS (Gulick, 1989). The tool consists of five subscales assessing; motor function, sensory disturbance, mental and emotional concerns, bowel function, bladder function, and brain stem symptomatology. Homogeneity reliability was identified through the use of Cronbach’s alpha with subscale scores ranging from .78 to .87 (Gulick, 1989). Scores are determined through the use of a six-point scale with responses ranging from never to always. Higher scores indicate the presence of increased symptomatology (Gulick, 1998). Here, only the total symptom score was utilized (Total MS Symptoms). Total scale homogeneity reliability as determined through Cronbach’s alpha in this study was .90.
The mean scores and standard deviations for all measures are provided in Table 1. Results are presented for both MS and control subject groups, as is the statistical analysis.
Results
The examination of data began with conducting Levine’s test for equality of variance. All mean comparison data between MS and control subjects demonstrated at least a .05 level of significance on the Levine’s, indicating the existence of non-normative patterns of distribution. All data was then examined using a non-parametric statistic, the Mann-Whitney U. In Table 1, the scores from the Mann-Whitney are given and indicated as such. The alpha level determined prior to analysis was p = .05. Further examination of the data was performed using partial correlations and structural model testing. All data analysis was conducted using Statistical Package for the Social Sciences (SPSS) Version 10.05, with the exception of structural model testing, which was conducted using Analysis of Moment Structures (AMOS) 4.0.
Sample Characteristics
Control subjects (N = 34) were between 29 and 54 years of age (M = 43.00, SD = 1.34). All control subjects were identified as Caucasian. Three control subjects were male while the remainder female (n = 31). MS subjects (N = 41) were between 28 and 75 years of age (M = 49.05, SD = 9.11) with 12 male subjects (28.6%) and 31 female subjects (71.4%). In those with MS, individuals identified as Caucasian (n = 38) comprised the majority of the sample (90.5%), with three subjects identified as African-American (7.1%) and one as American Indian. To ensure equality of groups in terms of age, and other demographic variables, independent t-tests and the Mann-Whitney U were performed to examine for the presence of significant variance in demographic variables. The Mann-Whitney U was performed on all nominal data (age, gender, race, and martial status). No significant differences were found between control and MS groups in terms of age, gender, race or martial status. A significant difference was found in terms of education, using a two-tailed t-test for independent samples (t = 4.349, 44, CI of 1.88 to 2.30, p < .01). Control subjects reported significantly more years of education (M = 18.70, SD = 1.34) than did MS subjects (M = 15.19, SD = 2.44).
Form of MS
Each MS subject was asked to self-report whether a sub-type, or form, of MS had been diagnosed. As the use of diagnostic categories has changed over time, individuals with a longer course of disease were often unable to specify a particular form of MS. These individuals were categorized as type unknown. Twenty-four (58.5%) individuals were identified as Relapsing-Remitting, seven (17.0%) as Chronic-Progressive, one as Benign, one as Progressive-Recurring and the remaining eight (19.5%) as Unknown.
In order to determine whether the reported form of MS accounted for variance in scores for psychological measures, serial two-tailed t-tests for independent samples were performed. To provide a sufficient number of subjects for valid comparison, all individuals with a progressive element to the disease process were placed into one group (progressive-recurring, chronic-progressive); labeled progressive disease. This group consisted of eight subjects who scores were compared with individuals who had the relapsing-remitting form of MS (n = 33). No significant mean differences were found to exist for any of the variables between forms of MS (Data not shown).
Perceived Stress and Mood
MS subjects reported significantly higher levels of perceived stress than control subjects. See Table 1. In conjunction with significantly higher levels of perceived stress, MS subjects also reported significantly higher scores on all measures of negative mood derived from the POMS; tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia and confusion-bewilderment. Scores from the negative mood subscales can be summed on the POMS, and the score from a positive mood subscale (vigor-activity) subtracted, to provide a measure of the total amount of negative mood experienced by the respondent (McNair et al., 1992). This score is referred to as the total mood disturbance score (POMS-TD). The total disturbance score for the MS sample was significantly higher than that of the control sample (See Table 1).
In association with significantly higher levels of perceived stress and negative mood, MS subjects also displayed a concomitant decrease in positive affect as measured by the vigor-activity subscale (POMS-V) of the POMS. MS subjects were found to score significantly lower than did control subjects.
PSS scores correlated significantly with POMS-TD scores in individuals with MS, as with control subjects. However, as shown in Table 2, in MS subjects the magnitude of correlation was greater. MS subjects demonstrated significant positive Pearson correlations between level of perceived stress and all negative mood states assessed by the POMS. Scores from the measure of positive mood and the vigor-activity subscale were significantly correlated with perceived stress in a negative manner.
The correlations between perceived stress (PSS) and the POMS subscale scores in the MS sample tended to be twice as strong as the same correlation in normative control subjects. For example, with total mood disturbance (POMS-TD) for normative controls, the correlation between PSS and the measure of total mood disturbance was .447. For the MS subjects, the Pearson correlation between PSS and POMS-TD was .797. Not only did perceived stress significantly correlate with measures of negative mood state in MS subjects (POMS Subscales), the magnitude of these correlations was far greater in those with MS than in normative control subjects.
Psychological Stress, Illness Uncertainty, and MS Symptomatology
The patterns of correlation among measures of negative mood (POMS subscales), perceived stress, total mood disturbance, and total MS symptoms are shown in Table 2. Each measure of negative mood was significantly correlated with reported MS symptomatology (MSSC). Perceived stress and total mood disturbance (POMS-TD) showed significant positive correlation with total MS symptomatology. The measure of positive affect, vigor-activity, was significantly correlated in a negative manner with total MS symptomatology.
Perceived stress and total mood disturbance were positively correlated with the measure of illness uncertainty (MUIS). Illness uncertainty (MUIS) scores of MS subjects were also positively correlated with the total number of MS symptoms. Illness uncertainty correlated selectively with other measures of negative mood, such as tension-anxiety and fatigue-inertia.
We sought to further examine the relationship among these variables by classifying MS subjects into high- and low-stress groups (See Table 3). The criteria determining high- versus low-stress classification was the median score for the PSS. Subjects were classified as high-stress if the PSS scores were at, or above, the median (≥ 20), while those subjects classified as low-stress were those with PSS scores below the median (< 20). A mean comparison was conducted using two-tailed t test for independent samples.
High-stress MS subjects displayed significantly higher scores on all measures of negative mood (tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia) and total mood disturbance than did low-stress MS subjects. The high-stress MS subjects were also found to display significantly lower scores on the measure of positive affect, vigor-activity, than did low-stress MS subjects. Those MS subjects identified as high stress, reported significantly higher levels of illness uncertainty than did low-stress MS subjects (see Table 3). High-stress MS subjects (n = 24) also reported a significantly higher level of disease symptoms than did low-stress MS subjects (n = 17). Additionally, high-stress MS subjects tended to have had a shorter period of disease (M 7.65 years, SD 6.65) as compared with low-stress MS subjects (M 14.16 years, SD 14.16). This finding may demonstrate that, as the individual grows more accustomed to living within the context of MS, illness uncertainty fades.
As part of the examination of the relationship between illness uncertainty, perceived stress, and MS symptoms, a series of partial correlations were performed in which illness uncertainty (MUIS) scores were held constant (see Table 4). There was little change in the significance of association of variables when MUIS scores were held constant, with correlations decreasing an average of .10.
The role of perceived stress is supported by the presence of a stronger positive correlation between PSS scores and total MS symptom report (r = .745, p = < .01); than that found between MUIS and total MS symptom report (r = .537). In addition, all of the POMS subscales correlated more strongly with total MS symptomatology than did illness uncertainty (Table 2), with the exception of fatigue-inertia.
In order to examine the relative contribution illness uncertainty made to variance in MS symptomatology, an exploratory structural model was constructed based upon previous conceptualizations of illness uncertainty (Mishel, 1981, 1984). A structural recursive model was created that included: illness uncertainty, perceived stress, total MS symptoms and total mood disturbance. Analysis was not conducted using separate mood states as derived from the POMS, for the total mood disturbance score is compiled through summation of negative mood states subscale scores with subtraction of the positive mood state subscale score. The inclusion of such constituent variables was then seen as raising the risk of inadvertent multicollinearity. Analysis was conducted using Amos 4.0, with illness uncertainty as an exogenous variable. Endogenous variables were perceived stress, total mood disturbance and MS symptomatology. The tested model exhibited acceptable fit, x2 (1, N = 80) = .842, p = .359. The tested model is presented in Figure 1, with standardized total effects.
Figure 1. Exploratory path analysis of the relationship among uncertainty, perceived stress, total mood disturbance, and total reported symptoms of multiple sclerosis.
Note: All numbers indicate Standardized Total Effects
Legend: Standardized total effects are presented for each variable, which is a combination of the direct (alone) and indirect (through influence on other variables) effect on MS symptoms for each study variable. Stress, mood disturbance, and illness uncertainty have small, but significant, direct effects on the experience of MS symptoms, with stronger indirect effects, implying that these variables exert a direct influence on the experience of symptoms in MS patients.
Illness uncertainty exhibited a small standardized direct effect (.18) on MS symptoms, while perceived stress demonstrated a slightly larger standardized direct effect (.28). Total mood disturbance exhibited a moderate standardized direct effect (.47). The standardized total effect for illness uncertainty on MS symptoms was weaker (.59) than that of perceived stress (.68). Such data, when taken in conjunction with the partial correlations indicate that the effects of illness uncertainty are predominantly indirect effects, perhaps occurring through the mediation of stress appraisal as originally conceptualized by Mishel. This is supported by a stronger standardized indirect effect for illness uncertainty (.41) than for perceived stress (.39). Other factors yet come to play, for illness uncertainty only explained 21% of the variance in perceived stress. Together, the three psychological variables (perceived stress, total mood disturbance, and illness uncertainty) explained 45% of the variance in MS symptoms.
Discussion
Previous investigators have demonstrated a relationship between heightened levels of perceived stress and clinical exacerbation in individuals with MS (Warren et al., 1991). Yet, many of these studies have not successfully linked levels of perceived stress to reported symptoms. Instead, stress has been linked to periods of disease exacerbation without evaluating the effect of stress on disease symptoms outside these periods. This study examined the contribution that perceived stress and illness uncertainty make to those symptoms reported by individuals with MS during a period of disease remission. In general, the findings of this study are consistent with previous research, which has demonstrated that MS subjects often display higher levels of psychological distress than normative controls (Ackerman, Martino, Heyman, Moyna, & Rabin, 1998; Jean, Beatty, Paul, & Mullins, 1997). MS subjects were found to have significantly higher levels of perceived stress and total mood disturbance than control subjects. MS subjects were also found to have indices of psychological distress (perceived stress, total mood disturbance, negative mood state) that correlated significantly with the incidence of disease symptomatology. Individuals with MS consistently displayed significantly higher scores on all psychological measures than normative controls with the exception of scores on the POMS subscale, vigor-activity. MS subjects consistently scored significantly lower than control subjects on vigor-activity. The effect of perceived stress may then involve more than the manifestation of negative mood, it may well involve a concomitant decrease in the experience of positive mood. Based on this data, we conclude that MS subjects experience a higher level of perceived stress and mood disturbance than control subjects. Indeed, MS subjects that were classified as low-stress displayed a higher mean PSS score (M 13.88, SD 4.39) than control subjects as a whole (M 11.37, SD 4.88). These findings indicate that MS subjects live and function within a heightened state of psychological stress, a state of psychological stress that has significant positive correlation with disease symptomatology.
The subjects classified as high-stress had significantly higher mean scores for measures of disease symptomatology, illness uncertainty, and total mood disturbance than low-stress MS subjects. The division of MS subjects based on level of perceived stress revealed significant differences not only in the scores for psychological variables, but also the importance of examining the influence of perceived stress on other psychological measures. The mean scores for those MS subjects classified as low-stress were lower than the means for illness uncertainty and total mood disturbance reported by other, larger, investigations (Wineman et al., 1996). Yet, the scores for MS subjects classified as high-stress were comparable with the scores found in that previous work. The mean illness uncertainty score in MS individuals classified as high-stress was roughly equitable to that found in previous investigations (M 69.08, SD 11.91). Wineman et al. (1994), found a mean MUIS score of 77.02 with a sample that was ten-fold the size of the present sample (N = 433). The scores on POMS-TD were much larger in the present study, with the high-stress population reporting a mean of 69.58. Whereas, Wineman et al., (1994), reported a mean POMS-TD score of 32.50. Such divergence in terms of mood disturbance and illness uncertainty may indicate the need to examine how differing samples of MS patients may vary in psychological stress scores. Those individuals with MS who experience high levels of stress may be more likely to experience disease exacerbation than those with lower levels of stress. There needs to be closer examination of those subjects with MS who do not report heightened levels of perceived stress, in terms of how these individuals may cope differently from those who report high levels of stress.
Living with a chronic disease that is associated with an uncertain course of progression in conjunction with existent levels of disability, could contribute to the development of a state of chronic psychological stress. Such a state of chronic psychological stress may tax or challenge the adaptive resources of the individual. Here we found that individuals with MS experience higher levels of perceived stress, perhaps due to higher levels of illness uncertainty. Illness uncertainty did correlate significantly with levels of perceived stress and select measures of negative affect (tension-anxiety, fatigue-inertia, total mood disturbance). The effects, however, of illness uncertainty on disease symptoms appeared more indirect and to occur through increased levels of perceived stress, rather than through a large main effect on the part of illness uncertainty itself. A stronger direct effect was found for perceived stress and total mood disturbance on MS symptoms than was found for illness uncertainty. In the conceptual model of Mishel, a higher degree of illness uncertainty could be a contributing factor to the stressful appraisal of an event or situation, dependent on whether the degree of uncertainty was perceived as a threat (Mishel, 1981). This conceptualization appears consistent with the data of this study; that the effects found for illness uncertainty appeared to occur through mediation of perceived stress.
Psychological stress in those with MS could occur as the result of a combination of negative life events and disease related variables (Aikens, Fischer, Namey, & Rudick, 1997). Dalos, Rabins, Brooks, and O’Donnell (1983) found that emotional disturbance was associated with increased disease activity in those with MS. The degree of physical disability present in those with MS has previously been shown to influence psychological functioning. The greater the level of symptomatology and correspondent disability: the greater the effects on the ability of the individual to function socially (Zedlow & Pavlou, 1984). For example, disease symptoms may; (1) increase in relation to states of negative affect and psychological distress or, (2) themselves cause increased levels of negative affect and psychological distress. Psychological stress could function in a circular manner, enhancing the impact of other life events and serving to precipitate disease, which then reinforces a continued state of psychological stress (LaRocca, 1984; Warren, 1990).
Conclusion
We have found that illness uncertainty and perceived stress are directly associated with increased MS symptom report, outside of periods of disease exacerbation. Based on these findings, it could be speculated that psychological factors may influence the daily experience of symptoms in individuals with MS. Perhaps the gradual worsening of symptoms in response to increased levels of perceived stress results in the development of a circular pattern of stress and disease. A pattern in which perceived stress contributes to increased symptomatology, which in turn affects the functional ability of the individual and increases levels of illness uncertainty, resulting in even greater levels of perceived stress, eventually leading to clinical exacerbation in the failure of effective coping mechanisms.
Implications for Spinal Cord Injury Nurses
The patient with MS encountered in the spinal cord setting is more apt to have significant disability, particularly in terms of ambulative ability and ability to perform activities of daily living. In turn, it is possible this patient may be experiencing higher levels of stress and illness related uncertainty. As perceived stress and illness uncertainty may influence the presence of MS symptoms, it is important to investigate with the patient and family feelings regarding stress and the use of coping strategies. The identification and teaching of appropriate and feasible coping strategies can aid the patient in coping with illness-related uncertainty and stress. Helping the patient cope more effectively can, at a minimum, contribute to an improved quality of life and just might have an effect on symptom presentation.
Acknowledgements
We thank Gastone Celesia and Amy Perrin-Ross for their invaluable assistance in the recruitment of subjects. We also wish to thank those individuals with, and without, MS who participated in this study. This project was partly supported by grants from the National Institutes of Health (NIH 1F31 NR07442), American Association of Spinal Cord Injury Nurses (Project Number 177), and Sigma Theta Tau–Alpha Beta Chapter.
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Mathew R. Sorenson, PhD, RN, is assistant professor of nursing at DePaul University, Chicago, Illinois. msorenson@depaul.edu
Linda Janusek, PhD, RN, is a professor of nursing At Loyala University, Chicago.
Herbert L. Mathews, PhD, is a professor of microbiology and immunology at Loyola Unversity, Chicago.