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partner report and disease course
Journal of Psychosomatic Research 66 (2009) 147 – 154
Personality traits in women with multiple sclerosis: Discrepancy in patient/partner report and disease course Ralph H.B. Benedict a,b,⁎, Elizabeth L. Wahlig c , Raluca A. Topciu d , Jessica Englert a,b , Eben Schwartz a,b , Ben Chapman d , Bianca Weinstock-Guttman a,b , Paul R. Duberstein d a
State University of New York at Buffalo School of Medicine, Departments of Neurology and Psychiatry, Buffalo, NY, USA b Jacobs Neurological Institute, Buffalo, NY, USA c Western New York Veterans Administration, Buffalo, NY, USA d Department of Psychiatry, Laboratory of Personality and Development, University of Rochester Medical Center, Rochester, NY, USA Received 18 December 2007; received in revised form 12 August 2008; accepted 4 September 2008
Abstract Objective: Patients diagnosed with multiple sclerosis (MS) are believed to undergo personality changes, which could have implications for how they perceive themselves and are perceived by others. We endeavored to examine the extent to which patients' self-perceptions are congruent with how they are perceived by significant others across five trait domains as demarcated by the well known Five-Factor Model (FFM). Methods: The NEO FiveFactor Inventory (NEOFFI) (Costa and McCrae, 1992) was administered to women with MS (n=70) and their spouses or partners. Pearson correlations and general linear models (GLMs) were employed to test for differences between patient self-reports and partner reports of FFM traits. Results: Correlation analyses revealed good correspondence between patient and partner NEOFFI data in relapsing-remitting MS patients, but not
secondary progressive patients. There was no significant correlation among progressive course patients for all NEOFFI domains, except Agreeableness. GLMs revealed significant differences where patients rated themselves higher than their partners rated them in Extraversion and Openness. Conclusion: These discrepancies in the way patients and partners view patient personality are probably multidimensional and may have neurological and/or psychological causes. The direction of the discrepancies are consistent with some prior research suggesting MS, which is a disease affecting both the cerebral white and gray matter, may give rise to lowering in self awareness. Conversely, patients may be finding emotional or personal benefits in their response to the disease unbeknownst to partners. © 2009 Elsevier Inc. All rights reserved.
Keywords: Multiple sclerosis; Personality; Neurologic disease; Five-factor model
Introduction Multiple sclerosis (MS) is a disease characterized by recurrent attacks of neurological symptoms followed by remission [1,2]. In the so-called relapsing-remitting (RR) phase of the illness, patients often resume their normal activity with minimal interference. However, over time, many patients show progressive decline in neurological status, despite a decrease in the frequency of relapses. This
⁎ Corresponding author. E-mail address: [email protected] (R.H.B. Benedict). 0022-3999/08/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jpsychores.2008.09.007
secondary progressive (SP) phase of the illness is far more disabling and presents a greater barrier to high quality of life [3,4]. Such neurological progression often takes the form of weakness, sensory loss, fatigue, and cognitive decline. Not surprisingly, progression of neurologic disability and cognitive impairment are linked to cerebral pathology, especially brain atrophy [5–7]. Like patients with other neurodegnenerative diseases [8–13], MS patients are suspected of personality changes [14–17] which might puzzle both patients and partners alike. Moreover, the unpredictable course of the disease poses a significant challenge to how patients think about themselves and could also affect how others perceive them [18–21].
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As an initial step in addressing the extent to which patients' self-perceptions are congruent with how they are perceived by significant others, we administered the NEO Five-Factor Inventory (NEOFFI) [22] to 70 women with MS and their spouses or partners. We sought to estimate the level of self-partner agreement and gain insight into particular areas of personality about which there may be disagreement. We reasoned that findings could help inform the clinical assessment and treatment of patients with MS and facilitate psychosocial support from their partners. Research on self-informant agreement in personality developed rapidly in the 1980s, with numerous studies conducted on nonpatient samples, typically students [23,24] or adults participating in the Baltimore Longitudinal Study of Aging [25]. These studies generally suggested that selfother agreement is substantial, with correlations as high as r=0.73 [22]. Studies of self-informant agreement in adult patients, conducted mainly in the context of psychiatric treatment, are generally consistent with research on normal samples, although correlations may be slightly lower [26– 29]. Specifically, relationships between self-reported traits and informant reports typically range from 0.30 to 0.60. Personality theory suggests that high levels of selfinformant agreement are adaptive and expectable [30]. Social relations, especially close personal relationships, are contingent on a shared capacity to perceive, decode, and interpret social and emotional signals and develop expectations about others' attitudes and behaviors, thoughts, and feelings across diverse contexts [30]. When low levels of self–other agreement are observed on personality inventories, differing interpretations of item wording and other relatively mundane issues could play a role [31]. Psychologically substantive considerations may also play a role in understanding discrepant perceptions, such as genuinely different views of the target and poor insight or neurological impairment on the part of either member of the dyad [32]. Other influences include the nature of the relationship; agreement between spouses tends to be higher than agreement between acquaintances [22], possibly reflecting the dual importance of both length of time the subject is known to the observer and the range of situations across which observers view subjects. Finally, there may be lower levels of agreement for traits that are relatively private, such as self-reproach, than those that are more readily observable, such as hostility [23]. Research with neurological patient samples has yielded levels of agreement which are somewhat lower than the levels observed in healthy populations [11,16,33,34]. Benedict et al. [16] examined patient and informant-reported NEO Personality Inventory profiles in MS patients, most of whom were cognitively impaired, and had moderate to severe neurological disability or progressive course. Significant differences were found with patients rating themselves as lower in neuroticism as compared to informant judgments, and higher in extraversion, agreeableness, and conscientiousness. The degree of discrepancy was positively correlated with the
extent of cognitive impairment. In a study of patients with traumatic brain injury [34], correlation between patient and informant reports were moderate, but there were also significant differences in mean neuroticism and conscientiousness scores, in the same direction as reported by Benedict et al. These studies highlight the possibility of significant differences between patients and informants in the perception of particular domains of patient personality and that such discrepancies are causally related to the severity of cognitive impairment and, by extension, cerebral injury. In designing the present study, we made two decisions intended to control for potential sources of measurement error that have rarely been addressed in prior research. First, the analyses were conducted on an all-female sample. Justification for this decision includes the higher prevalence of MS in women [35] and the presence of gender differences in personality [36–38]. Second, we controlled for the nature of the relationship between patient and informant by restricting the analyses to informant data provided by men who were married to or living “as if married” with the patient. Personality was assessed via the NEOFFI [22]. Development of that scale was grounded in the natural language and factor analytic approaches to personality assessment [39,40]. The model reflects general consensus [41], but not complete agreement [42], that the adjectives used to describe human traits, attitudes, and behaviors can be grouped along five orthogonal dimensions [30,41]. These domains have most often been named Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. Neuroticism refers to a person's stress reactivity or emotional responsiveness to challenge and proclivity for negative mood states such as anxiety or worry. Extraversion is the dependence upon external stimulation for arousal and tendency to be outgoing, sensation seeking, and to be inclined to positive mood states such as joy and cheerfulness. Openness is the desire for novelty, including yearning for exposure to new knowledge, ideas, and experiences. Agreeableness refers to one's proclivity for social cooperation, honesty and altruism. Finally, Conscientiousness is the extent to which a person is task-oriented, achievement-striving, deliberate, dependable, careful, and organized. Arguments have been made for the routine assessment of the Five-Factor Model (FFM) traits to guide psychosomatic research [36,43,44]. In this study, we administered two versions of the NEOFFI. One version, completed by the patient, was developed for self-report. The other, completed by the male partners, was identical except that it contained third person pronouns. Beyond determining the extent of agreement between women with MS and their spouses, we were interested in identifying particular traits that might generate higher levels of disagreement and may thus have implications for quality of life. Our general and guiding hypothesis was that more advanced, more progressive disease would be associated with greater divergence between the reports of patients and their informants.
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Method Participants The participants were 70 Caucasian dyads (patient and spouse/partner; the latter is hereafter referred to as “partner”) recruited from the neurology clinic affiliated with a university hospital. The majority (48% or 68%) were referred for psychological assessment for routine monitoring (n=31) of psychological status or to examine a specific clinical problem such as vocational disability (n=17). The remaining patients volunteered and were paid to undergo evaluation of cognitive status and personality (n=22). A multivariate analysis of variance comparing patient-informant discrepancies across all personality traits revealed that the degree of discrepancy did not differ across recruitment venue [Wilks Lambda F(10,126)=0.9, P=.531]. Informed consent was obtained as directed by the university institutional review board. Exclusion criteria were (a) history of medical or psychiatric disorder other than MS that could affect cognitive or personality function prior to MS onset, including mood disorders; (b) current major depressive episode by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria; (c) current substance abuse; (d) neurological impairment that may interfere with psychometric testing; and (e) MS relapse or corticosteroid pulse within 6 weeks of participation. Major depression was assessed via structured interview based on the DSM-IV, administered prior to participation [45]. We selected only female patients living with a male spouse or partner. Mean (±S.D.) age of the patients was 47.2±9.9 years with a range of 26–65 years. Mean education was 13.6±1.9 years with a range of 10–18 years. The patients were diagnosed by neurologists specializing in the care of MS patients using commonly accepted diagnostic criteria [46]. Mean disease duration, based on reported date of diagnosis and confirmed by chart review, was 12.9±8.2 with a range of 1–38 years. Disease course [47] was as follows: 44 relapsing-remitting (RR), 26 secondary progressive (SP; one patient had questionable relapsing vs secondary progressive course). Expanded Disability Status Scale (EDSS) [48] obtained within 6 months of testing was available from neurology clinic notes on 44 patients. The median EDSS was 3.0, and the range was 1 to 6.5. The MS Functional Composite [49,50], available for all patients, included three components: First, the Paced Auditory Serial Addition Test (sample mean 40.0 ±14.2) assessed mental processing speed. Second, the NineHole Peg Test (dominant hand 21.9±5.0; nondominant hand 23.8±6.4) assessed manual speed and dexterity. Third, the Timed 25 Foot Walk (7.6±8.2) assessed gait, strength and agility in the lower extremities. Scores from these measures were incorporated into the commonly accepted formula [49,50] to derive a total z score reflecting the degree of neurological disability. The mean Multiple Sclerosis Functional Composite Measure (MSFC) z score was -0.02+0.68,
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and the range was -2.09 to 1.39. We also compared the mean values for each component to healthy controls with similar demographics to this MS sample [51]. As is commonly observed in MS, lower extremity dysfunction was most prominent (mean z score=−5.9) whereas mental processing speed was more mildly affected (mean z score=−0.9). Beck Depression Inventory-Fast Screen [52] was obtained, and the mean was 2.8±2.7. Regarding medications, 60 (85.7%) patients were taking disease-modifying medications, 39 (55.7%) were taking antidepressants, and 20 (28.6%) were taking anxiolytics or anticonvulsants. No patients were taking antipsychotics. Materials and procedure The patients were either scheduled for a clinical appointment or approached by the clinic staff and asked to undergo brief cognitive (cognitive data to be examined in future work and analysis) and personality testing which included the NEOFFI. This is a 60-item questionnaire based on the Five-Factor Model. Each of the five domains is measured by responses to 12 questions, using a five-point scale. The entire test requires roughly 30 min to complete. The NEOFFI has acceptable to excellent reliability [22] with the mean reliability coefficient being 0.75 [53]. The validity of the test is well established in that it correlates significantly with similar personality tests [22] and predicts a range of health outcomes [43,54]. The self-report version was completed by patients, and the informant-report version, by their partners. The patients and their partners were separated from one another throughout the psychometric examination, which was carried out in a single session in the same clinic where the patients were being treated for MS. Statistical analyses Descriptive statistics for all study variables were calculated. To examine patient-spouse/partner agreement, Pearson correlation coefficients were calculated for domains of the NEOFFI: Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness for all patients, and then separately for RR and SP patients. In addition, correlations between demographics and MSFC, and the NEOFFI patient/partner difference scores were calculated. Due to the large number of correlations, we used a conservative alpha of Pb.01 as a threshold for statistical significance. Fisher's r-to-z transformation was used to assess for statistically significant differences of independent correlations. General linear models (GLMs) were used to test for these patient/partner differences on NEOFFI domain scores. As the patient and partner were rating the same person (i.e., the patient), the NEOFFI scores were treated as a repeated measures factor. The potential influence of neurological disability was explored by including MSFC as a covariate in the analysis. Next, to test for the influence of disease course,
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we included RR vs. SP as a dichotomous between-groups factor in a final set of GLMs. Where significance was found at the level of the five overall NEOFFI domains, we measured NEOFFI domain component scores derived from different combinations of NEOFFI items that are clustered to yield subcomponents of each general domain [55,56]. Components of Neuroticism are labeled Anxiety, Depression, and Self-Reproach; Extraversion components are Positive Affect, Sociability, and Activity; for Openness, components are Aesthetic Interests, Intellectual Interests, and Unconventionality; Nonantagonistic Orientation and Prosocial Orientation make up the Agreeableness domain; and Orderliness, Goal-Striving, and Dependability comprise the Conscientiousness domain. Results Coefficient alphas were .81 for Neuroticism, .75 for Extraversion, .68 for Openness, .77 for Agreeableness, and .84 for Conscientiousness for patient self-report, and for informant reports, .87 for Neuroticism, .82 for Extraversion, .68 for Openness, .91 for Agreeableness, and .91 for Conscientiousness. Pearson correlations among the five NEOFFI domains for patient and partner scores are reported in Table 1. Correlations between the five domains were not significant or modest in degree, reflecting the independence of the five factors measured using the NEOFFI. We do note, however, that the correlations were stronger among the partner report data—Agreeableness was positively correlated with Extraversion and Conscientiousness and negatively correlated with Neuroticism. There were no statistically significant correlations between NEOFFI patient/partner difference scores and age, education, or MSFC. As shown in Table 2, patient self-report and partner report showed good agreement as indicated by Pearson correlation coefficients. All correlations were statistically significant when either the whole sample or the RR patients were assessed. However, for SP patients, the correlations were substantially weaker, and in all but one case (Agreeableness),
Table 1 Pearson correlation comparing the linear association among NEOFFI domain scores N Neuroticism Extraversion Openness Agreeableness Conscientiousness
⁎−0.39 −0.01 −0.27 ⁎−0.34
E ⁎−0.35 0.27 0.14 ⁎0.32
O
A
C
−0.17 ⁎0.39
⁎−0.52 ⁎0.50 0.27
−0.29 ⁎0.44 ⁎0.34 ⁎0.56
−0.01 0.21
0.17
N, neuroticism; E, extraversion; O, openness; A, agreeableness; C, conscientiousness. Bottom left of table represents correlations for patient self-report and the top right of the table represents the partner report correlations. ⁎ Pb.01.
Table 2 Pearson correlations between patient self-report and partner report NEOFFI scores
Neuroticism Extraversion Openness Agreeableness Conscientiousness
Whole Sample
RR Disease Course
SP Disease Course
⁎0.41 ⁎0.51 ⁎0.42 ⁎0.49 ⁎0.31
⁎0.55 ⁎0.69 ⁎0.45 ⁎0.45 ⁎0.44
0.15 0.17 0.38 ⁎0.54 0.15
⁎ Pb.01.
not statistically significant. When these correlations were subjected to the Fisher test for differences of independent correlations, the patient-partner correlations for Extraversion were significantly different between RR and SP patients, z=2.6, Pb.005. The correlations for the other domains were not significantly different. When domain score differences were submitted to analysis of variance, significant differences emerged on the Extraversion and Openness domains (Table 3). The direction of the effect was such that partners described patients as less extraverted and open than the patients described themselves. Adding MSFC as a covariate to each model did not significantly change the outcome. The mixed-factor GLMs with disease course treated as a between-groups factor also yielded two significant results. Again, there were no significant findings for Neuroticism, Agreeableness, or Conscientiousness. The Extraversion model revealed a significant effect or patient/partner report [F(1,68)=11.733, P=.001], and the main effect for course and the interaction effect was not significant. The same was true for the Openness model where the patient/partner main effect was the only significant result [F(1,68)=11.28, P=.001]. Finally, analyses of variance examined the component scores from Extraversion (Positive Affect, Sociability, Activity) and Openness (Aesthetic Interests, Intellectual Interests, Unconventionality). The effects are displayed in Fig. 1. It can be seen that for each component, partners described patients as lower in these content areas. The effects were statistically significant for Activity [F(1,69)=11.24, P=.001], Aesthetic Interests [F(1,69)=7.22, P=.009], and Intellectual Interests [F(1,69)=8.82, P=.004].
Discussion Despite the likelihood of disease-related personality change [14–17] and the unpredictability of the course of disease, we find that MS patients and their partners have a shared understanding of the patients' emotions, behavioral patterns, and attitudes that define and constitute three major personality domains: Neuroticism, Agreeableness, and Conscientiousness. Moreover, the level of patient-partner agreement, operationally defined via the correlation
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Table 3 Univariate analyses of variance
Neuroticism Extraversion Openness Agreeableness Conscientiousness
Patient report (M)
Patient report (S.D.)
Partner report (M)
Partner report (S.D.)
r
F
P
22.00 27.19 25.26 34.80 32.74
7.92 6.24 5.58 6.11 7.33
23.11 24.31 22.79 33.67 32.97
8.91 7.51 5.66 9.06 8.74
0.41 0.51 0.42 0.49 0.31
1.03 12.03 11.58 1.36 0.04
.314 .001 .001 .248 .841
All r values are significant at Pb.001, except for SP patients where Neuroticism, Extraversion, Openness, and Conscientiousness are not statistically significant.
coefficient, is similar to prior reports on most other patient samples [28,29], and the mean levels of self-reported traits are generally consistent with published norms [22]. However, among SP patients, nonsignificant or poor correlation between patient and partner reports was observed within the domains of Neuroticism, Extraversion, Openness, and Conscientiousness. In addition, discrepancies in patient/ partner reports of Extraversion and Openness were observed. If the unpredictable course of the disease poses a significant challenge to how patients think about themselves and affects how others perceive them, it would need to be said that the effects are most prominent within the Extraversion and Openness domains. While these constructs are orthogonal, generally speaking, they both involve activity and the willingness to venture into new social or physical pursuits. Discrepancies between patients and partners in the way they view patient personality may reflect personality changes that are more evident to partners than they are to the patients themselves. There may be an unmasking of latent personality traits with the unfolding of cerebral disease in MS [7]. Alternatively, discrepancies may be attributed to the spouses' expectations or unfounded beliefs about what patients with MS are supposed to “look like,” combined with changes in relational dynamics arising from living with the disease on a daily basis. A potential clue in this regard comes from the findings that Extraversion and Openness may represent a higher-order factor, termed beta or plasticity, while the
Fig. 1. Presented are component raw scores derived from the Extraversion and Openness domains of the NEOFFI. Error bars refer to S.D.
remaining domains form a higher order factor alpha or stability [40,57]. The plasticity factor reflects active exploration of the social (Extraversion) and internal (Openness) environment, reward dependence (Extraversion), and flexibility (Openness) related to exploration for novel input. Such an inclination may be particularly salient and adaptive among patients with neurological disease. Another intriguing possibility is that certain personality traits are phenotypic representations of genetic vulnerabilities or protective factors in relation to neurological illness. These and other hypotheses will require longitudinal research including the repeated assessment of personality in MS. We have planned such a study which will include concordant measures of neurological disability and cognition. Other explanations for the discrepancies require closer inspection of the domains affected. Extraversion refers to the degree to which a person depends on external stimulation for arousal and the desire for stimulating activity [22]. Openness refers to the preference for novelty [22]. Of the FFM personality domains, Extraversion is the most closely related to social and physical activity, and Openness is most closely tied to intelligence. There may be methodological explanations for the observation that women with MS rated themselves as higher in these domains than their partners rated them. For Extraversion, patients may be using a different reference point for comparing their level of activity. Patients may feel that their activity level is high for a person with the physical limitations of MS, while partner raters do not account for disability in the same way. One could also can argue that Openness has fewer observable, fixed behavioral referents than the other personality domains, as it is more concerned with the inner life—imagination and fantasy as well as attitudes, beliefs, and values that may be relatively private. Partners may simply not have access to good information [58] about the trait. This methodological explanation cannot account for the finding that poor correlation between patients and partners was particularly evident among dyads managing more severe disease, those with a secondary progressive course. Indeed, the most significant finding in our report may be that the degree of patient/informant discrepancy is related to disease course. In other MS work, we have found that discrepancies in the report of neuropsychiatric disturbance among patients was also associated with progressive disease course [7,17,33]. In each of the studies, the pattern was the
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same—patients with progressive course were more apt to underestimate neuropsychiatric symptoms and report higher levels of Extraversion, Openness, Agreeableness, or Conscientiousness than informants. We speculate that progressive course is associated with brain atrophy which may, in turn, lead to not only personality change but lack of selfawareness or anosagnosia [7]. This relationship, if confirmed, may be mediated by cognitive impairment, a hypothesis under investigation by our group. On the other hand, these patient ratings may constitute a benefit-finding strategy [19] that provides comfort and consolation with the belief that, despite progressive neurological disability, they remain intellectually curious and socially engaged. Two items loading on the Mohr et al. [19] index of benefit finding would presumably be related to Openness but not readily apparent to observers: “I have become more spiritual” and “I have become more introspective.” Our finding that the Openness effect was driven mostly by aesthetic and intellectual interests is consistent with this interpretation. Mohr et al. suggested that increased compassion and greater respect for others may be unexpected benefits of MS. In other words, the disease may provide a new “window on the world;” it is not merely or always a burden, deficit, or weakness but an opportunity to develop a new, unconventional, and “softer” way of perceiving and experiencing the world, stimulating greater compassion and empathy. If indeed the observed patient/ partner discrepancies for Openness reflect benefit finding, partners may lag behind in appreciating or deriving such benefit from the disease. Another psychological explanation that should not be overlooked involves qualitative change in the spousal relationship which may develop over time in MS patient/partner dyads. We should not lose sight of the fact that some caregivers of MS patients may develop psychological adjustment problems themselves as caregiver demands increase. The reader will note that our findings do not fully replicate the prior work of Benedict et al. [16] who reported larger effects and significant self/informant report differences in four FFM domains. This earlier sample was composed of MS patients with more severe neurological disability (range 1.0–8.5) and mostly progressive course (65%). In addition, Benedict et al. included informant reports from caregivers having a wide range of relationship to the patient, including parents and friends. Thus, the smaller effects seen here may reflect less severe and disabling disease, and/or the closer relationships between patients and their spouses. Our findings and speculations must be qualified by several limitations. First, no direct comparisons were made between our sample and matched controls, although we were able to compare the mean scores with published benchmarks. Future studies could include control and comparison samples and consider designs that permit self- and informant-report ratings before symptoms or soon after diagnosis. Without prospective data collection, it cannot be known whether
observed self-partner differences predated the onset or diagnosis of disease. It is assumed that the discrepancies instead reflect disease processes, including pathophysiological changes as well as changes in attitudes and behavioral patterns that amount to shifts in self-concept that are observable on personality inventories. Second, data on potentially important informant characteristics were not collected. Informant reports may be influenced by an array of unmeasured processes, including, for example, frustration with the patient's increased dependency needs, which could lead to a negative bias in reporting patient personality. Third, the observed differences may be less about the static content of the trait being assessed and more about the relational dynamics between patients and their partners/spouses. Finally, while the gender homogeneity of our sample controls for gender differentially impacting discrepancies across domains of personality, we cannot exclude the possibility that gender may have contributed to patient/ partner rating discrepancies in general. These limitations are outweighed by the study's strengths, chief of which are its novelty and design. Our findings open up new areas of inquiry and point to the need for research on the implications for quality of life, relationship satisfaction, and social functioning of differing perspectives on patient personality. A methodological strength of the study is the use of the NEOFFI, which provides a comprehensive trait taxonomy. Other strengths were the use of a wellcharacterized sample of patients and a research design that enabled us to control simultaneously for patient gender and the nature of the relationship between patient and informant while examining discrepancies across all FFM domains. In summary, we report significant discrepancies between self and informant rated personality traits measured by the NEOFFI that are, in part, related to MS disease course. Further exploration is clearly warranted, with greater attention paid to the influence of informant characteristics and interpersonal dynamics. Prospective research on the implications of differing perceptions of Extraversion or Openness on patients' personal relationships and possibly the nature and quality of care they receive may be particularly interesting. Acknowledgments Work on this manuscript was supported by United States Public Health Service Grants K24MH072712, R21AG023956, and T3MH207452. References [1] McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Nuerol 2001;50:121–7. [2] Lublin FD, Reingold SC, Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey.
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Personality traits in women with multiple sclerosis: Discrepancy in patient/partner report and disease course Ralph H.B. Benedict a,b,⁎, Elizabeth L. Wahlig c , Raluca A. Topciu d , Jessica Englert a,b , Eben Schwartz a,b , Ben Chapman d , Bianca Weinstock-Guttman a,b , Paul R. Duberstein d a
State University of New York at Buffalo School of Medicine, Departments of Neurology and Psychiatry, Buffalo, NY, USA b Jacobs Neurological Institute, Buffalo, NY, USA c Western New York Veterans Administration, Buffalo, NY, USA d Department of Psychiatry, Laboratory of Personality and Development, University of Rochester Medical Center, Rochester, NY, USA Received 18 December 2007; received in revised form 12 August 2008; accepted 4 September 2008
Abstract Objective: Patients diagnosed with multiple sclerosis (MS) are believed to undergo personality changes, which could have implications for how they perceive themselves and are perceived by others. We endeavored to examine the extent to which patients' self-perceptions are congruent with how they are perceived by significant others across five trait domains as demarcated by the well known Five-Factor Model (FFM). Methods: The NEO FiveFactor Inventory (NEOFFI) (Costa and McCrae, 1992) was administered to women with MS (n=70) and their spouses or partners. Pearson correlations and general linear models (GLMs) were employed to test for differences between patient self-reports and partner reports of FFM traits. Results: Correlation analyses revealed good correspondence between patient and partner NEOFFI data in relapsing-remitting MS patients, but not
secondary progressive patients. There was no significant correlation among progressive course patients for all NEOFFI domains, except Agreeableness. GLMs revealed significant differences where patients rated themselves higher than their partners rated them in Extraversion and Openness. Conclusion: These discrepancies in the way patients and partners view patient personality are probably multidimensional and may have neurological and/or psychological causes. The direction of the discrepancies are consistent with some prior research suggesting MS, which is a disease affecting both the cerebral white and gray matter, may give rise to lowering in self awareness. Conversely, patients may be finding emotional or personal benefits in their response to the disease unbeknownst to partners. © 2009 Elsevier Inc. All rights reserved.
Keywords: Multiple sclerosis; Personality; Neurologic disease; Five-factor model
Introduction Multiple sclerosis (MS) is a disease characterized by recurrent attacks of neurological symptoms followed by remission [1,2]. In the so-called relapsing-remitting (RR) phase of the illness, patients often resume their normal activity with minimal interference. However, over time, many patients show progressive decline in neurological status, despite a decrease in the frequency of relapses. This
⁎ Corresponding author. E-mail address: [email protected] (R.H.B. Benedict). 0022-3999/08/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jpsychores.2008.09.007
secondary progressive (SP) phase of the illness is far more disabling and presents a greater barrier to high quality of life [3,4]. Such neurological progression often takes the form of weakness, sensory loss, fatigue, and cognitive decline. Not surprisingly, progression of neurologic disability and cognitive impairment are linked to cerebral pathology, especially brain atrophy [5–7]. Like patients with other neurodegnenerative diseases [8–13], MS patients are suspected of personality changes [14–17] which might puzzle both patients and partners alike. Moreover, the unpredictable course of the disease poses a significant challenge to how patients think about themselves and could also affect how others perceive them [18–21].
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As an initial step in addressing the extent to which patients' self-perceptions are congruent with how they are perceived by significant others, we administered the NEO Five-Factor Inventory (NEOFFI) [22] to 70 women with MS and their spouses or partners. We sought to estimate the level of self-partner agreement and gain insight into particular areas of personality about which there may be disagreement. We reasoned that findings could help inform the clinical assessment and treatment of patients with MS and facilitate psychosocial support from their partners. Research on self-informant agreement in personality developed rapidly in the 1980s, with numerous studies conducted on nonpatient samples, typically students [23,24] or adults participating in the Baltimore Longitudinal Study of Aging [25]. These studies generally suggested that selfother agreement is substantial, with correlations as high as r=0.73 [22]. Studies of self-informant agreement in adult patients, conducted mainly in the context of psychiatric treatment, are generally consistent with research on normal samples, although correlations may be slightly lower [26– 29]. Specifically, relationships between self-reported traits and informant reports typically range from 0.30 to 0.60. Personality theory suggests that high levels of selfinformant agreement are adaptive and expectable [30]. Social relations, especially close personal relationships, are contingent on a shared capacity to perceive, decode, and interpret social and emotional signals and develop expectations about others' attitudes and behaviors, thoughts, and feelings across diverse contexts [30]. When low levels of self–other agreement are observed on personality inventories, differing interpretations of item wording and other relatively mundane issues could play a role [31]. Psychologically substantive considerations may also play a role in understanding discrepant perceptions, such as genuinely different views of the target and poor insight or neurological impairment on the part of either member of the dyad [32]. Other influences include the nature of the relationship; agreement between spouses tends to be higher than agreement between acquaintances [22], possibly reflecting the dual importance of both length of time the subject is known to the observer and the range of situations across which observers view subjects. Finally, there may be lower levels of agreement for traits that are relatively private, such as self-reproach, than those that are more readily observable, such as hostility [23]. Research with neurological patient samples has yielded levels of agreement which are somewhat lower than the levels observed in healthy populations [11,16,33,34]. Benedict et al. [16] examined patient and informant-reported NEO Personality Inventory profiles in MS patients, most of whom were cognitively impaired, and had moderate to severe neurological disability or progressive course. Significant differences were found with patients rating themselves as lower in neuroticism as compared to informant judgments, and higher in extraversion, agreeableness, and conscientiousness. The degree of discrepancy was positively correlated with the
extent of cognitive impairment. In a study of patients with traumatic brain injury [34], correlation between patient and informant reports were moderate, but there were also significant differences in mean neuroticism and conscientiousness scores, in the same direction as reported by Benedict et al. These studies highlight the possibility of significant differences between patients and informants in the perception of particular domains of patient personality and that such discrepancies are causally related to the severity of cognitive impairment and, by extension, cerebral injury. In designing the present study, we made two decisions intended to control for potential sources of measurement error that have rarely been addressed in prior research. First, the analyses were conducted on an all-female sample. Justification for this decision includes the higher prevalence of MS in women [35] and the presence of gender differences in personality [36–38]. Second, we controlled for the nature of the relationship between patient and informant by restricting the analyses to informant data provided by men who were married to or living “as if married” with the patient. Personality was assessed via the NEOFFI [22]. Development of that scale was grounded in the natural language and factor analytic approaches to personality assessment [39,40]. The model reflects general consensus [41], but not complete agreement [42], that the adjectives used to describe human traits, attitudes, and behaviors can be grouped along five orthogonal dimensions [30,41]. These domains have most often been named Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. Neuroticism refers to a person's stress reactivity or emotional responsiveness to challenge and proclivity for negative mood states such as anxiety or worry. Extraversion is the dependence upon external stimulation for arousal and tendency to be outgoing, sensation seeking, and to be inclined to positive mood states such as joy and cheerfulness. Openness is the desire for novelty, including yearning for exposure to new knowledge, ideas, and experiences. Agreeableness refers to one's proclivity for social cooperation, honesty and altruism. Finally, Conscientiousness is the extent to which a person is task-oriented, achievement-striving, deliberate, dependable, careful, and organized. Arguments have been made for the routine assessment of the Five-Factor Model (FFM) traits to guide psychosomatic research [36,43,44]. In this study, we administered two versions of the NEOFFI. One version, completed by the patient, was developed for self-report. The other, completed by the male partners, was identical except that it contained third person pronouns. Beyond determining the extent of agreement between women with MS and their spouses, we were interested in identifying particular traits that might generate higher levels of disagreement and may thus have implications for quality of life. Our general and guiding hypothesis was that more advanced, more progressive disease would be associated with greater divergence between the reports of patients and their informants.
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Method Participants The participants were 70 Caucasian dyads (patient and spouse/partner; the latter is hereafter referred to as “partner”) recruited from the neurology clinic affiliated with a university hospital. The majority (48% or 68%) were referred for psychological assessment for routine monitoring (n=31) of psychological status or to examine a specific clinical problem such as vocational disability (n=17). The remaining patients volunteered and were paid to undergo evaluation of cognitive status and personality (n=22). A multivariate analysis of variance comparing patient-informant discrepancies across all personality traits revealed that the degree of discrepancy did not differ across recruitment venue [Wilks Lambda F(10,126)=0.9, P=.531]. Informed consent was obtained as directed by the university institutional review board. Exclusion criteria were (a) history of medical or psychiatric disorder other than MS that could affect cognitive or personality function prior to MS onset, including mood disorders; (b) current major depressive episode by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria; (c) current substance abuse; (d) neurological impairment that may interfere with psychometric testing; and (e) MS relapse or corticosteroid pulse within 6 weeks of participation. Major depression was assessed via structured interview based on the DSM-IV, administered prior to participation [45]. We selected only female patients living with a male spouse or partner. Mean (±S.D.) age of the patients was 47.2±9.9 years with a range of 26–65 years. Mean education was 13.6±1.9 years with a range of 10–18 years. The patients were diagnosed by neurologists specializing in the care of MS patients using commonly accepted diagnostic criteria [46]. Mean disease duration, based on reported date of diagnosis and confirmed by chart review, was 12.9±8.2 with a range of 1–38 years. Disease course [47] was as follows: 44 relapsing-remitting (RR), 26 secondary progressive (SP; one patient had questionable relapsing vs secondary progressive course). Expanded Disability Status Scale (EDSS) [48] obtained within 6 months of testing was available from neurology clinic notes on 44 patients. The median EDSS was 3.0, and the range was 1 to 6.5. The MS Functional Composite [49,50], available for all patients, included three components: First, the Paced Auditory Serial Addition Test (sample mean 40.0 ±14.2) assessed mental processing speed. Second, the NineHole Peg Test (dominant hand 21.9±5.0; nondominant hand 23.8±6.4) assessed manual speed and dexterity. Third, the Timed 25 Foot Walk (7.6±8.2) assessed gait, strength and agility in the lower extremities. Scores from these measures were incorporated into the commonly accepted formula [49,50] to derive a total z score reflecting the degree of neurological disability. The mean Multiple Sclerosis Functional Composite Measure (MSFC) z score was -0.02+0.68,
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and the range was -2.09 to 1.39. We also compared the mean values for each component to healthy controls with similar demographics to this MS sample [51]. As is commonly observed in MS, lower extremity dysfunction was most prominent (mean z score=−5.9) whereas mental processing speed was more mildly affected (mean z score=−0.9). Beck Depression Inventory-Fast Screen [52] was obtained, and the mean was 2.8±2.7. Regarding medications, 60 (85.7%) patients were taking disease-modifying medications, 39 (55.7%) were taking antidepressants, and 20 (28.6%) were taking anxiolytics or anticonvulsants. No patients were taking antipsychotics. Materials and procedure The patients were either scheduled for a clinical appointment or approached by the clinic staff and asked to undergo brief cognitive (cognitive data to be examined in future work and analysis) and personality testing which included the NEOFFI. This is a 60-item questionnaire based on the Five-Factor Model. Each of the five domains is measured by responses to 12 questions, using a five-point scale. The entire test requires roughly 30 min to complete. The NEOFFI has acceptable to excellent reliability [22] with the mean reliability coefficient being 0.75 [53]. The validity of the test is well established in that it correlates significantly with similar personality tests [22] and predicts a range of health outcomes [43,54]. The self-report version was completed by patients, and the informant-report version, by their partners. The patients and their partners were separated from one another throughout the psychometric examination, which was carried out in a single session in the same clinic where the patients were being treated for MS. Statistical analyses Descriptive statistics for all study variables were calculated. To examine patient-spouse/partner agreement, Pearson correlation coefficients were calculated for domains of the NEOFFI: Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness for all patients, and then separately for RR and SP patients. In addition, correlations between demographics and MSFC, and the NEOFFI patient/partner difference scores were calculated. Due to the large number of correlations, we used a conservative alpha of Pb.01 as a threshold for statistical significance. Fisher's r-to-z transformation was used to assess for statistically significant differences of independent correlations. General linear models (GLMs) were used to test for these patient/partner differences on NEOFFI domain scores. As the patient and partner were rating the same person (i.e., the patient), the NEOFFI scores were treated as a repeated measures factor. The potential influence of neurological disability was explored by including MSFC as a covariate in the analysis. Next, to test for the influence of disease course,
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we included RR vs. SP as a dichotomous between-groups factor in a final set of GLMs. Where significance was found at the level of the five overall NEOFFI domains, we measured NEOFFI domain component scores derived from different combinations of NEOFFI items that are clustered to yield subcomponents of each general domain [55,56]. Components of Neuroticism are labeled Anxiety, Depression, and Self-Reproach; Extraversion components are Positive Affect, Sociability, and Activity; for Openness, components are Aesthetic Interests, Intellectual Interests, and Unconventionality; Nonantagonistic Orientation and Prosocial Orientation make up the Agreeableness domain; and Orderliness, Goal-Striving, and Dependability comprise the Conscientiousness domain. Results Coefficient alphas were .81 for Neuroticism, .75 for Extraversion, .68 for Openness, .77 for Agreeableness, and .84 for Conscientiousness for patient self-report, and for informant reports, .87 for Neuroticism, .82 for Extraversion, .68 for Openness, .91 for Agreeableness, and .91 for Conscientiousness. Pearson correlations among the five NEOFFI domains for patient and partner scores are reported in Table 1. Correlations between the five domains were not significant or modest in degree, reflecting the independence of the five factors measured using the NEOFFI. We do note, however, that the correlations were stronger among the partner report data—Agreeableness was positively correlated with Extraversion and Conscientiousness and negatively correlated with Neuroticism. There were no statistically significant correlations between NEOFFI patient/partner difference scores and age, education, or MSFC. As shown in Table 2, patient self-report and partner report showed good agreement as indicated by Pearson correlation coefficients. All correlations were statistically significant when either the whole sample or the RR patients were assessed. However, for SP patients, the correlations were substantially weaker, and in all but one case (Agreeableness),
Table 1 Pearson correlation comparing the linear association among NEOFFI domain scores N Neuroticism Extraversion Openness Agreeableness Conscientiousness
⁎−0.39 −0.01 −0.27 ⁎−0.34
E ⁎−0.35 0.27 0.14 ⁎0.32
O
A
C
−0.17 ⁎0.39
⁎−0.52 ⁎0.50 0.27
−0.29 ⁎0.44 ⁎0.34 ⁎0.56
−0.01 0.21
0.17
N, neuroticism; E, extraversion; O, openness; A, agreeableness; C, conscientiousness. Bottom left of table represents correlations for patient self-report and the top right of the table represents the partner report correlations. ⁎ Pb.01.
Table 2 Pearson correlations between patient self-report and partner report NEOFFI scores
Neuroticism Extraversion Openness Agreeableness Conscientiousness
Whole Sample
RR Disease Course
SP Disease Course
⁎0.41 ⁎0.51 ⁎0.42 ⁎0.49 ⁎0.31
⁎0.55 ⁎0.69 ⁎0.45 ⁎0.45 ⁎0.44
0.15 0.17 0.38 ⁎0.54 0.15
⁎ Pb.01.
not statistically significant. When these correlations were subjected to the Fisher test for differences of independent correlations, the patient-partner correlations for Extraversion were significantly different between RR and SP patients, z=2.6, Pb.005. The correlations for the other domains were not significantly different. When domain score differences were submitted to analysis of variance, significant differences emerged on the Extraversion and Openness domains (Table 3). The direction of the effect was such that partners described patients as less extraverted and open than the patients described themselves. Adding MSFC as a covariate to each model did not significantly change the outcome. The mixed-factor GLMs with disease course treated as a between-groups factor also yielded two significant results. Again, there were no significant findings for Neuroticism, Agreeableness, or Conscientiousness. The Extraversion model revealed a significant effect or patient/partner report [F(1,68)=11.733, P=.001], and the main effect for course and the interaction effect was not significant. The same was true for the Openness model where the patient/partner main effect was the only significant result [F(1,68)=11.28, P=.001]. Finally, analyses of variance examined the component scores from Extraversion (Positive Affect, Sociability, Activity) and Openness (Aesthetic Interests, Intellectual Interests, Unconventionality). The effects are displayed in Fig. 1. It can be seen that for each component, partners described patients as lower in these content areas. The effects were statistically significant for Activity [F(1,69)=11.24, P=.001], Aesthetic Interests [F(1,69)=7.22, P=.009], and Intellectual Interests [F(1,69)=8.82, P=.004].
Discussion Despite the likelihood of disease-related personality change [14–17] and the unpredictability of the course of disease, we find that MS patients and their partners have a shared understanding of the patients' emotions, behavioral patterns, and attitudes that define and constitute three major personality domains: Neuroticism, Agreeableness, and Conscientiousness. Moreover, the level of patient-partner agreement, operationally defined via the correlation
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Table 3 Univariate analyses of variance
Neuroticism Extraversion Openness Agreeableness Conscientiousness
Patient report (M)
Patient report (S.D.)
Partner report (M)
Partner report (S.D.)
r
F
P
22.00 27.19 25.26 34.80 32.74
7.92 6.24 5.58 6.11 7.33
23.11 24.31 22.79 33.67 32.97
8.91 7.51 5.66 9.06 8.74
0.41 0.51 0.42 0.49 0.31
1.03 12.03 11.58 1.36 0.04
.314 .001 .001 .248 .841
All r values are significant at Pb.001, except for SP patients where Neuroticism, Extraversion, Openness, and Conscientiousness are not statistically significant.
coefficient, is similar to prior reports on most other patient samples [28,29], and the mean levels of self-reported traits are generally consistent with published norms [22]. However, among SP patients, nonsignificant or poor correlation between patient and partner reports was observed within the domains of Neuroticism, Extraversion, Openness, and Conscientiousness. In addition, discrepancies in patient/ partner reports of Extraversion and Openness were observed. If the unpredictable course of the disease poses a significant challenge to how patients think about themselves and affects how others perceive them, it would need to be said that the effects are most prominent within the Extraversion and Openness domains. While these constructs are orthogonal, generally speaking, they both involve activity and the willingness to venture into new social or physical pursuits. Discrepancies between patients and partners in the way they view patient personality may reflect personality changes that are more evident to partners than they are to the patients themselves. There may be an unmasking of latent personality traits with the unfolding of cerebral disease in MS [7]. Alternatively, discrepancies may be attributed to the spouses' expectations or unfounded beliefs about what patients with MS are supposed to “look like,” combined with changes in relational dynamics arising from living with the disease on a daily basis. A potential clue in this regard comes from the findings that Extraversion and Openness may represent a higher-order factor, termed beta or plasticity, while the
Fig. 1. Presented are component raw scores derived from the Extraversion and Openness domains of the NEOFFI. Error bars refer to S.D.
remaining domains form a higher order factor alpha or stability [40,57]. The plasticity factor reflects active exploration of the social (Extraversion) and internal (Openness) environment, reward dependence (Extraversion), and flexibility (Openness) related to exploration for novel input. Such an inclination may be particularly salient and adaptive among patients with neurological disease. Another intriguing possibility is that certain personality traits are phenotypic representations of genetic vulnerabilities or protective factors in relation to neurological illness. These and other hypotheses will require longitudinal research including the repeated assessment of personality in MS. We have planned such a study which will include concordant measures of neurological disability and cognition. Other explanations for the discrepancies require closer inspection of the domains affected. Extraversion refers to the degree to which a person depends on external stimulation for arousal and the desire for stimulating activity [22]. Openness refers to the preference for novelty [22]. Of the FFM personality domains, Extraversion is the most closely related to social and physical activity, and Openness is most closely tied to intelligence. There may be methodological explanations for the observation that women with MS rated themselves as higher in these domains than their partners rated them. For Extraversion, patients may be using a different reference point for comparing their level of activity. Patients may feel that their activity level is high for a person with the physical limitations of MS, while partner raters do not account for disability in the same way. One could also can argue that Openness has fewer observable, fixed behavioral referents than the other personality domains, as it is more concerned with the inner life—imagination and fantasy as well as attitudes, beliefs, and values that may be relatively private. Partners may simply not have access to good information [58] about the trait. This methodological explanation cannot account for the finding that poor correlation between patients and partners was particularly evident among dyads managing more severe disease, those with a secondary progressive course. Indeed, the most significant finding in our report may be that the degree of patient/informant discrepancy is related to disease course. In other MS work, we have found that discrepancies in the report of neuropsychiatric disturbance among patients was also associated with progressive disease course [7,17,33]. In each of the studies, the pattern was the
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same—patients with progressive course were more apt to underestimate neuropsychiatric symptoms and report higher levels of Extraversion, Openness, Agreeableness, or Conscientiousness than informants. We speculate that progressive course is associated with brain atrophy which may, in turn, lead to not only personality change but lack of selfawareness or anosagnosia [7]. This relationship, if confirmed, may be mediated by cognitive impairment, a hypothesis under investigation by our group. On the other hand, these patient ratings may constitute a benefit-finding strategy [19] that provides comfort and consolation with the belief that, despite progressive neurological disability, they remain intellectually curious and socially engaged. Two items loading on the Mohr et al. [19] index of benefit finding would presumably be related to Openness but not readily apparent to observers: “I have become more spiritual” and “I have become more introspective.” Our finding that the Openness effect was driven mostly by aesthetic and intellectual interests is consistent with this interpretation. Mohr et al. suggested that increased compassion and greater respect for others may be unexpected benefits of MS. In other words, the disease may provide a new “window on the world;” it is not merely or always a burden, deficit, or weakness but an opportunity to develop a new, unconventional, and “softer” way of perceiving and experiencing the world, stimulating greater compassion and empathy. If indeed the observed patient/ partner discrepancies for Openness reflect benefit finding, partners may lag behind in appreciating or deriving such benefit from the disease. Another psychological explanation that should not be overlooked involves qualitative change in the spousal relationship which may develop over time in MS patient/partner dyads. We should not lose sight of the fact that some caregivers of MS patients may develop psychological adjustment problems themselves as caregiver demands increase. The reader will note that our findings do not fully replicate the prior work of Benedict et al. [16] who reported larger effects and significant self/informant report differences in four FFM domains. This earlier sample was composed of MS patients with more severe neurological disability (range 1.0–8.5) and mostly progressive course (65%). In addition, Benedict et al. included informant reports from caregivers having a wide range of relationship to the patient, including parents and friends. Thus, the smaller effects seen here may reflect less severe and disabling disease, and/or the closer relationships between patients and their spouses. Our findings and speculations must be qualified by several limitations. First, no direct comparisons were made between our sample and matched controls, although we were able to compare the mean scores with published benchmarks. Future studies could include control and comparison samples and consider designs that permit self- and informant-report ratings before symptoms or soon after diagnosis. Without prospective data collection, it cannot be known whether
observed self-partner differences predated the onset or diagnosis of disease. It is assumed that the discrepancies instead reflect disease processes, including pathophysiological changes as well as changes in attitudes and behavioral patterns that amount to shifts in self-concept that are observable on personality inventories. Second, data on potentially important informant characteristics were not collected. Informant reports may be influenced by an array of unmeasured processes, including, for example, frustration with the patient's increased dependency needs, which could lead to a negative bias in reporting patient personality. Third, the observed differences may be less about the static content of the trait being assessed and more about the relational dynamics between patients and their partners/spouses. Finally, while the gender homogeneity of our sample controls for gender differentially impacting discrepancies across domains of personality, we cannot exclude the possibility that gender may have contributed to patient/ partner rating discrepancies in general. These limitations are outweighed by the study's strengths, chief of which are its novelty and design. Our findings open up new areas of inquiry and point to the need for research on the implications for quality of life, relationship satisfaction, and social functioning of differing perspectives on patient personality. A methodological strength of the study is the use of the NEOFFI, which provides a comprehensive trait taxonomy. Other strengths were the use of a wellcharacterized sample of patients and a research design that enabled us to control simultaneously for patient gender and the nature of the relationship between patient and informant while examining discrepancies across all FFM domains. In summary, we report significant discrepancies between self and informant rated personality traits measured by the NEOFFI that are, in part, related to MS disease course. Further exploration is clearly warranted, with greater attention paid to the influence of informant characteristics and interpersonal dynamics. Prospective research on the implications of differing perceptions of Extraversion or Openness on patients' personal relationships and possibly the nature and quality of care they receive may be particularly interesting. Acknowledgments Work on this manuscript was supported by United States Public Health Service Grants K24MH072712, R21AG023956, and T3MH207452. References [1] McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Nuerol 2001;50:121–7. [2] Lublin FD, Reingold SC, Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey.
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