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Stressful Life Events Precede Exacerbations of Multiple Sclerosis
Abstract
We longitudinally monitored life events and health changes in patients with multiple sclerosis (MS) to determine whether stressful events may trigger exacerbation of MS.
Twenty-three women with MS were followed for 1 year. Each subject completed the Psychiatric Epidemiologic Research Interview on a weekly basis. Further information on potentially stressful events was acquired using the Life Events and Difficulties Schedule. Neurologic symptoms were also monitored on a weekly basis throughout the year. Potential MS exacerbations were confirmed by a neurologist who was blind to the presence and timing of stressors.
Eighty-five percent of MS exacerbations were associated with stressful life events in the preceding 6 weeks. Stressful life events occurred an average of 14 days before MS exacerbations, compared with 33 days before a randomly selected control date (p < .0001). Survival analysis confirmed that an increase in frequency of life events was associated with greater likelihood of MS exacerbations (hazard ratio = 13.18, p < .05).
These results are consistent with the hypothesis that stress is a potential trigger of disease activity in patients with relapsing-remitting MS.
... While for MS patients the performance peaks at the second block and then declines until the fourth block, it finds its maximum for the healthy control subjects at the third block and then declines slightly to fourth block. Block-specific performance in TVA processing speed (C) for MS patients (MS) and healthy controls (CG).To test the associations between processing speed and subjective fatigue, a repeated measures ANCOVA of the processing speed performance was conducted with the withinsubject-factor block performance(1)(2)(3)(4) and the between-subject-factor subjective-fatiguegroup (MFIS>38 = high vs. MFIS≤38 = low), and age as a co-variable. ...
... the MS group, average performance for the healthy control group differed not significantly between any blocks, for varying only slightly during the task.For subjective fatigue (MFIS cognition score; median-split > 38), repeated measures ANCOVA of the perceptual threshold performance with inner-subject-factor block performance(1)(2)(3)(4) and between-subject-factor subjective-fatigue-group, and the co-variable age, showed a tendential effect on the blocks of the whole report paradigm(F(3, 78)= 2.445; p=.07) and a significant effect for the interaction block x subjective-fatigue-group (F(3, 78) = 4.344, p < .01). For objective fatigue, a repeated measures ANOVA of the perceptual threshold Performance with the inner-subject-factor block performance (1-4) and the between-subject-factor objective-fatigue-group (PASAT3<1.11 ...
... p=n.s.). For objective fatigue, a repeated measures ANOVA of the visual short-term memory performance with the innersubject-factor block performance(1)(2)(3)(4) and the between-subject-factor objective-fatigue-group (PASAT3<1.11 = high vs. ...
Multiple sclerosis (MS(1)) is a diffusely disseminated inflammatory disease affecting widespread cerebral networks. Major cognitive impairments are a reduction of processing capacity and mental fatigue, i.e., an "abnormal sense of tiredness or lack of energy". Here, the present study provides the first assessment of the distinct components of visual processing capacity based on a 'theory of visual attention' (TVA(2)) in MS patients and relates it to measures of subjective as well as (more) objective fatigue. The performance of 36 relapsing-remitting MS patients in a whole report task of brief letter arrays was compared to healthy control subjects matched for gender, age and education. Additionally, the sustained attention test PASAT-3(3) served as a measure of objective fatigue, and the self-report questionnaire MFIS(4) as a measure of subjective fatigue. Results indicate generally diminished processing speed as well as iconic memory buffers, and increased perceptual thresholds in MS patients compared to healthy controls. Block-wise analysis of attentional parameters shows that the processing speed performance of MS patients declines in the second half of the TVA-based test compared to healthy controls and in particular for patients with high versus low objective fatigue. These findings describe which aspects of processing capacity are impaired in MS, and show that fatigue mainly affects speed of processing. Thus, TVA-based assessment provides a novel approach in the determination of cognitive impairments and fatigue in MS. However, further research is required to elucidate the complex relations of processing capacity and cognitive functions in MS.
... Finally, in a recent systematic review, Artemiadis et al. (2011) found that 15 of 17 studies reported a significant stress-MS relationship; however, they pointed out that the heterogeneity in the measurement of stress precluded secure conclusions. Other authors highlight the need to identify factors that might modify the stress-MS association (Ackerman et al., 2002;Brown et al., 2006b). All these reviews focused on the quality and main results of the studies, but none examined the results in function of the way stress was measured or of potential moderators and mediators. ...
... Table 1 reports the main characteristics of the selected papers. When we grouped papers according to whether they evaluated the effects of stress on onset or progression, we found 9 papers evaluating the effects of stress on onset (Grant et al., 1989;Liu et al., 2009;Mei-Tal et al., 1970;Nielsen et al., 2014aNielsen et al., , 2014bPalumbo et al., 1998;Pratt, 1951;Riise et al., 2011;Warren et al., 1982) and 14 evaluating the effects on disease progression, of which 13 focused on relapses (Ackerman et al., 2002(Ackerman et al., , 2003Brown et al., 2006aBrown et al., , 2006bBuljevac et al., 2003;Gasperini et al., 1995;Mitsonis et al., 2008Mitsonis et al., , 2010Mohr et al., 2000Mohr et al., , 2002Oveisgharan et al., 2014;Potagas et al., 2008;Warren et al., 1991) and 1 on health status (Schwartz et al., 1999). ...
... The 14 studies examining the relationship between stress and progression of MS were all prospective; 12 of these were cohort studies (Ackerman et al., 2002(Ackerman et al., , 2003Brown et al., 2006aBrown et al., , 2006bBuljevac et al., 2003;Mitsonis et al., 2008Mitsonis et al., , 2010Mohr et al., 2000Mohr et al., , 2002Oveisgharan et al., 2014;Potagas et al., 2008;Schwartz et al., 1999) and 2 were case-control studies (Gasperini et al., 1995;Warren et al., 1991). The duration of these studies ranged from 28 weeks to 8 years, but in most it was about 1 year. ...
Research about the effects of stress on multiple sclerosis has yielded contradictory results. This study aims to systematically review the evidence focusing on two possible causes: the role of stress assessment and potential moderating and mediating factors. The Web of Knowledge (MEDLINE and Web of Science), Scopus, and PsycINFO databases were searched for relevant articles published from 1900 through December 2014 using the terms “stress*” AND “multiple sclerosis.” Twenty-three articles were included. Studies focused on the effect of stress on multiple sclerosis onset (n = 9) were mostly retrospective, and semi-structured interviews and scales yielded the most consistent associations. Studies focused on multiple sclerosis progression (n = 14) were mostly prospective, and self-reported diaries yielded the most consistent results. The most important modifying factors were stressor duration, severity, and frequency; cardiovascular reactivity and heart rate; and social support and escitalopram intake. Future studies should consider the use of prospective design with self-reported evaluations and the study of moderators and mediators related to amount of stress and autonomic nervous system reactivity to determine the effects of stress on multiple sclerosis.
... This deterministic Stress Response may explain the inconclusiveness or negation of some earlier research [14][15][16][17] as the precedent step, distress, was not sufficiently or uniquely accounted for. This paper reports the results of the investigation into how distress induces MS symptom sets [18][19][20], documents the probability distributions characteristic of the disease, proposes several new statistical responses correlated with symptom production, and establishes that distress does induce MS symptom sets. The scope of the paper does not include the pathology of the Stress Response resulting in the inducement or action of Effectors, or of Disease Processes leading to Injury. ...
... Since, a relapse consists of one or more symptom sets, the upper bound of a relapse duration D U,R would be the maximum of all symptom sets i to n, with duration upper bound D U,i plus the time t i between relapse start and start of this symptom set, i.e (18) Where t i is determined by the i th trigger event, with the Haz- ari Data Set, t i -t i-1 is determined by equation (4), and D U,i is determined by equation (17). However, as a symptom within a symptom set may have reduced but not ended, there is a residual symptom. ...
... No caso da vulnerabilidade, a predisposição genética para doenças degenerativas pode ser ativada pela imunossupressão decorrente da cronificação das reações neurofisiológicas, o que torna o estresse um facilitador das patologias (e.g. a relação entre o estresse e o desencadeamento da esclerose múltipla) (Ackerman et al., 2002;Beeney & Arnet, 2008;McEwen, 2008;Olff, 199). Finalmente, Selye (1993) enfatizou que as doenças adaptativas não eram derivadas do estressor ou do estresse propriamente dito, mas da inadequação das reações, tendo em vista que a cadeia de repercussão neurofisiológica é composta por respostas estereotipadas (e.g. ...
... Sobre isso, Cottington, Matthews, Talbott e Kuller (1980), ao analisarem a relação entre EVE e casos de morte súbita em mulheres, encontraram que aquelas que morreram subitamente tinham uma chance seis vezes maior de terem perdido alguém significativo em um período de seis meses antes do falecimento. Recentemente, Ackerman et al. (2002) constataram que a presença de EVE é um preditor da exarcerbação dos sintomas de esclerose múltipla (80% em seis meses) e eleva a chance de piora no quadro em cerca de 13 vezes em um espaço de 15 dias. ...
This narrative review aimed to outline the conceptual evolution of stress, covering theoretical and methodological aspects of the three main areas of study, defined here as the response-based perspective, the stimulus-based perspective and the cognitive perspective. In addition, we sought to present a proposal for a conceptualization of stress according to the contemporary viewpoint of studies and the empirical evidences about the phenomenon, aiming to foster debate and encourage the production of research designs that consider issues studied in health psychology and interface areas. Thus, it seeks to highlight the historical development of the theory of stress, one of the most common forms of study of the health-illness process and of human capacity for adaptation in researches of psychology and health.
... These values are clearly greater than those of 10%-15% expected for the general population [7]. Previous studies have reported that depression may negatively influence the quality of life of patients [8], lead to suicidal behavior [9] and could also affect the disease course [10][11][12]. ...
... Furthermore, it must be considered that depression is a complex phenomenon in which interactions should also be considered bidirectionally, at least when psychological variables are taken into account. For example, the obvious consideration would be that disease features (disability, relapse frequency, pharmacological therapies etc.) can lead to the development of depressive symptoms; nevertheless, there is evidence that subjects with depression may experience a less favorable disease course [10][11][12]. The same mechanism would be predictable also for disease perception: subjects with poor perception of their health status could be more prone to the development of depression, and depression itself would influence subsequent ideation about the disease. ...
Background and purpose:
Depression is common amongst subjects with multiple sclerosis (MS), and several investigations have explored different determinants of this condition, including physical disability, psychological and psychosocial factors. The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with depression. The aim of this study was to analyze the influence of disease-related factors, BDNF Val66Met polymorphism and perception of disease on the severity of depression in MS.
Method:
In total, 136 MS patients (88 women) were recruited and genotyped for BDNF rs6265 polymorphism at nucleotide 196 (G/A) using 'high resolution melting'. Depressive symptoms were assessed by the Multiple Sclerosis Depression Rating Scale. Perception of health status was assessed using the SF-36 questionnaire.
Results:
A multivariable linear regression model showed that the best predictors of depression were the SF-36 General health (β = -0.209; P = 0.013), Mental health (β = -0.410; P < 0.001) and Social activity (β = -0.195; P = 0.035) scores; physical disability (assessed by the Extended Disability Status Scale score) was directly correlated to depression severity on univariate analysis, but it was not a relevant predictor of depression on multivariate analysis; other variables directly related to the disease (treatment, annual relapsing rate) and the BDNF Val66Met polymorphism were not significantly associated with depression.
Conclusion:
Perception of the health status is the principal predictor of depressive symptoms in our sample. This result supports the hypothesis that the subjective interpretation of the disease's consequences is one of the main factors in determining depression in MS.
... The longevity risk of major depression has been estimated as 50% in patients with MS (26,65), which can be compared with major depression risk in the general population as 10-15% of evaluated cases (66). Based on the high prevalence of this condition, patients' well-being and quality of life importance (67) (69)(70)(71)(72), depression in MS has been extensively studied. However, several focused and brief studies have been conducted (6,56). ...
Mood disorders could be frequently observed in multiple sclerosis (MS) patients. Mood disorders are common condition in multiple sclerosis with high prevalence rates, for example annually prevalence rate of depression is as high as 20% and lifetime prevalence rates is 50%. In addition it observed that bipolar disoder and other cognitive disorders were common in these patients. However, the comorbidity of psychiatric problems and amont of brain damage is not clear. Therfore, this study aimed to investigate the correlation between the active plaques of MS cases' brain MRI and co-occurrence of different cognitive disorders in the same patients. This literature review project was designed based on standard guidelines to evaluate the related data about brain MRI active plaques and cognitive disorders in multiple sclerosis. The study words, which were combined with each other, were "Mood Disorders", "Active Plaques", "Multiple Sclerosis", "MRI", "Depression", "Cognitive disorders", and "Bipolar Disorder", the data were extracted and compared. The evaluated studies have represented that there is a correlation between depression and the amount of active plaques on the anterior parietal and left temporal area of the MS patients.
... Furthermore, the stressful life events may alter immune function and affect susceptibility to autoimmune diseases including MS [9]. Several studies have demonstrated that stressful life events might have an adverse effect on the MS risk [10][11][12][13]. Though, the mechanisms by which such stressors trigger pathogenetic events in MS hitherto are unknown [11,13,14]. ...
Objective
It has been reasoned that stressful life events tend to alter immune function thereby increasing the susceptibility to autoimmune diseases including multiple sclerosis (MS). Using the database of Kuwait National MS Registry, this quasi-experimental study assessed the impact of the first Gulf War (Iraqi invasion of Kuwait in 1990) on MS risk in Kuwait.
Methods
MS incidence data from 1980 to 2019 were obtained from the Kuwait National MS Registry. Annual age-standardized incidence rates (ASIRs) (per 10⁵ person-years) were computed using the World Standard Population as a reference. Interrupted time series analysis with the option of autoregressive order (1) was used to evaluate the impact of the first Gulf War on MS risk by treating 1990 as an intervention year.
Results
Estimated baseline annual ASIR (per 10⁵ person-years) was 0.38 (95% CI: -1.02, 1.78; p = 0.587). MS ASIRs (per 10⁵ person-years) tended to increase significantly every year prior to 1990 by 0.45 (ASIR per 10⁵ person-years = 0.45; 95% CI: 0.15, 0.76; p = 0.005). During the first year of the first Gulf War, there seemed to be a non-significant increase (step change) in ASIRs (per 10⁵ person-years) of MS (ASIR per 10⁵ person-years = 0.85; 95% CI: − 5.16, 6.86; p = 0.775) followed by a non-significant increase in the annual trend in MS ASIRs per 10⁵ person-years (relative to the preintervention trend i.e., the difference between the pre-first Gulf War versus the post-first Gulf War trends) by 0.65 (ASIR per 10⁵ person-years = 0.65; 95% CI: − 0.22, 1.52; p = 0.138). However, a postestimation measure of the post-first Gulf War trend was statistically significant (ASIR per 10⁵ person-years = 1.10; 95% CI: 0.40, 1.80; p = 0.003), which implies that the post-first Gulf War trend in the annual ASIRs (per 10⁵ person-years) inclined to be the same as was the pre-first Gulf War (i.e., counterfactual of the pre-first Gulf War trend in annual ASIRs (per 10⁵ person-years) as if no first Gulf War took place).The Durbin-Watson test statistic (d = 1.89) showed almost non-significant autocorrelations across the time series observations on ASIRs (per 10⁵ person-years).
Conclusions
This study suggests that the first Gulf War was not significantly associated with the increasing trend in MS risk at population level in Kuwait neither with any short-term change nor with secular trend. Future studies may consider confirming the role of conflict-related stress or other stressful life events in potential exacerbation of MS risk along with unraveling biologically plausible mechanistic pathways.
... As a dynamic process, it needs to be assessed repeatedly over time. Studies addressing the relationship between stress and MS have mainly used selfadministered questionnaires [20,21,25,27,28] or weekly self-reported diaries [29,30]. However, most of them measured stress only once, and only a few considered stress-related factors (for a review, see Briones-Buixassa et al., 2015) [8]. ...
Objective:
The present study aims to analyse the bidirectional hypothesis between stress and multiple sclerosis with several measures of stress, impairment and functionality, considering also the interaction role of stress-related psychosocial factors such as anxiety, coping and social support.
Methods:
A one-year follow-up was conducted with 26 people with multiple sclerosis. Participants reported i) at baseline, anxiety (State-Trait Anxiety Inventory), and social support (Multidimensional Scale of Perceived Social Support); ii) daily, Ecological Momentary Assessment through self-reported diaries of stressful events and coping strategies; iii) monthly, the perceived stress (Perceived Stress Scale), iv) trimonthly, the self-reported functionality (Functionality Assessment in multiple sclerosis) and v) at baseline and at the end, neurologist rated impairment (Expanded Disability Status Scale). Mixed-effect regression models were conducted.
Results:
The bidirectional hypothesis was confirmed with perceived stress and self-reported functionality, which were negatively related in both directions. Coping and anxiety showed an interaction effect: active coping increased functionality only with high levels of stress, and high-trait anxiety showed lower functionality whereas low-trait anxiety showed higher functionality but only with low stress levels.
Conclusion:
People with multiple sclerosis may benefit from different types of psychological therapies, from gold-standard therapies like Cognitive Behavioural Therapy to third-waves therapies like Dialectical Behaviour Therapy or mindfulness, that focus on dealing with stress and affective symptoms, adjusting to the disease, and to improving their overall quality of life. More research is needed in this field under the biopsychosocial model.
... The relationship between demyelination in areas of the limbic system and depressive symptoms was suggested by studies in multiple sclerosis (MS) patients, who display increased risk of depression and anxiety (Habek et al., 2006;Pham et al., 2018;Rocca et al., 2018;Sanders and van Lieshout, 1992;Simpson et al., 2016). Moreover, stress is known to alter the course of MS, including precipitating relapse during symptom remittance and exacerbation (Ackerman et al., 2002;Buljevac et al., 2003;Mitsonis et al., 2008). Exposure of adult mice to CVS, social isolation, or CSDS also revealed overall decreased myelin transcript levels (Bonnefil et al., 2019;Lehmann et al., 2017;Liu et al., 2012Liu et al., , 2018, although important differences were observed between the distinct stress models. ...
Stress disorders are leading causes of disease burden in the U.S. and worldwide, yet available therapies are fully effective in less than half of all individuals with these disorders. Although to date, much of the focus has been on neuron-intrinsic mechanisms, emerging evidence suggests that chronic stress can affect a wide range of cell types in the brain and periphery, which are linked to maladaptive behavioral outcomes. Here, we synthesize emerging literature and discuss mechanisms of how non-neuronal cells in limbic regions of brain interface at synapses, the neurovascular unit, and other sites of intercellular communication to mediate the deleterious, or adaptive (i.e., pro-resilient), effects of chronic stress in rodent models and in human stress-related disorders. We believe that such an approach may one day allow us to adopt a holistic “whole body” approach to stress disorder research, which could lead to more precise diagnostic tests and personalized treatment strategies.
Stress is a major risk factor for many psychiatric disorders. Cathomas et al. review new insight into how non-neuronal cells mediate the deleterious effects, as well as the adaptive, protective effects, of stress in rodent models and human stress-related disorders.
... In 85-90% of cases of MS, there are courses of exacerbation of symptoms and recovery, but the process of the disease is unpredictable and it is known today that psychological tensions cause the activation of this disease [4]. A longitudinal study by Ackerman et al. [5] on 23 women with MS which followed for 1 year, specified that 85% of MS exacerbations were associated with stressful life events in the preceding 6 weeks and stress was proposed to be an activating factor in the disease recurrence. Recent reports from the American Neurological Association also show that one of the most important exacerbating factors of MS is the stress resulting from life events. ...
Background
Stress can be regarded as one of the consequences of Multiple Sclerosis (MS) and a factor in exacerbating or recurring the symptoms resulting from the disease. This study aimed to explain the stress coping behaviors in patients with MS based on the PRECEDE model.
Methods
This study is a qualitative directed content analysis research based on the PRECEDE model. Data were obtained through in-depth semi-structured interviews with 26 patients with MS, who were selected using a purposive sampling and maximum diversity in terms of gender, age, education, marital status, and employment. Data collection continued until the saturation occurred. Simultaneously, collected data were analyzed using a qualitative directed content analysis method.
Results
Data analysis led to the identification of 11 sub-categories. Of these, 10 sub-categories were assigned to three categories of predisposing factors (awareness, attitude, self-efficacy, and perceived severity), enabling factors (existence of resources, access to resources, skills of using resources, and educational preferences), and reinforcing factors (social support, important others and behavioral consequences). The social comparison category was a new category identified from the analysis of interviews.
Conclusions
Based on the results, individual, environmental and social factors play a role in the stress of these patients. Designing programs that lead to their empowerment and improvements in the environmental and social conditions can be effective in controlling stress in these patients. Based on the results, planners can adopt the most appropriate strategies to change these determinants, help reduce stress, and promote the psychological standard of living in these patients.
... Some studies report exacerbations after several weeks after the onset of stress. 24,37,38 Stressful events or perceived stress may be linked to the development of new Gd+ MR lesions. 39 In the study of Burns et al 40 showed that major negative, stressful events were associated with increased risk for subsequent Gd+ and new or enlarging T 2 lesions, while positive stressful events were associated with decreased. ...
Purpose
Multiple sclerosis (MS) is one of the most common neurological disorders and a cause of disability in young adults. Adequate stress management in MS patients may merit the benefits of both physical and psychological well-being. This study aimed to evaluate the quality of life in MS patients and its correlation with stress levels and coping strategies.
Methods
This descriptive and correlational study was conducted among 109 patients diagnosed with relapsing-remitting MS (RRMS). The study was based on a questionnaire designed by the authors and the following standardized questionnaires: the Perceived Stress Scale (PSS-10), the Inventory for Measuring Coping with Stress (Mini-COPE), and the Multiple Sclerosis International Quality of Life Questionnaire (MusiQoL).
Results
Data analysis showed that 47.71% of the patients experienced a high level of stress, and the most often used strategies under challenging situations included seeking emotional support (2.11) and active coping (1.96). Also, it showed that when the level of stress is higher, the QOL in all domains is lower. Coping strategies such as sense of humor, turning to religion, self-distraction, denial, venting, substance use, behavioral disengagement, and self-blame are negatively correlated with the quality of life of MS.
Conclusion
Quality of life in MS patients is negatively affected by a higher level of perceived stress. The use of coping strategies such as active coping, positive reframing, acceptance, and seeking emotional and instrumental support is positively correlated with the quality of life of MS patients.
... 31 Perceived racial or ethnic discrimination may also potentially impact the course of MS as a stressful event. 32 Future studies need to be designed to address these broader, more complicated issues. ...
Background
Multiple sclerosis (MS) results in considerable financial burdens due to expensive treatment and high rates of disability, which could both impact care non-adherence.
Objective
To measure financial toxicity in MS patients, identify its predictors and association with care non-adherence.
Methods
Adult MS patients visiting neurology clinic (June 2018 to February 2019) were consented to complete a survey. Financial toxicity was measured using Comprehensive Score for Financial Toxicity (COST) (range: 0–44, the lower the score, the worse the financial toxicity). Independent predictors of financial toxicity were identified using linear regression. Associations of COST score with patient outcomes were assessed.
Results
The mean COST score in 243 recruited patients was 17.4 ± 10.2. In response to financial burdens, 66.7% and 34.7% reported life-style altering behaviors or care non-adherence, respectively. Higher financial self-efficacy was associated with less financial toxicity (coefficient, 1.33 (95% confidence interval (CI), 1.02–1.64); p < 0.001). At least one relapse in the last 3 months was associated with greater financial toxicity (coefficient, −3.34 (95% CI, −6.66 to −0.01); p = 0.049). Greater financial toxicity correlated with life-style-altering coping strategy use (p < 0.001), care non-adherence (p = 0.001), and worse health-related quality of life (HRQOL) (p = 0.03).
Conclusion
MS patients with lower financial self-efficacy and prior relapse history are at higher risk for financial toxicity, with associated care non-adherence and lower HRQOL.
... Nonetheless, individuals with MS frequently report that stress exacerbates their symptoms. 26 Some evidence also suggests stress may exacerbate the MS disease process, resulting in more frequent relapses and increased lesion activity visible on MRI. 27,28 In addition to mindfulness (described below), stress inoculation training (CBT and relaxation training), and stressfocused group-based self-management have been shown to be beneficial. ...
Importance:
Multiple sclerosis (MS) is a complex and unpredictable neurologic disease affecting nearly 1 million people in the US. People with MS commonly experience multiple physical and psychological symptoms such as depression, anxiety, stress, fatigue, and pain that impact functioning and quality of life. Subsequently, living with MS requires routine management of MS symptoms, adaptation to challenges, and engagement in health behaviors to promote well-being over time.
Observations:
There is considerable evidence that behavioral interventions that increase cognitive and/or behavioral skills to address the challenges of day-to-day life with MS can promote resilience and reduce overall distress associated with this chronic and unpredictable disease. Brief group-based cognitive-behavioral therapy (CBT) and CBT-based interventions (eg, self-management) have been shown to reduce symptoms of depression, anxiety, stress, fatigue, and pain in people with MS, including via telehealth delivery. Likewise, mindfulness-based interventions have been shown to improve depression, anxiety, stress, fatigue, and quality of life in people with MS. Behavioral interventions also have been shown to improve health behaviors such as physical activity and adherence to disease modifying therapies in MS. Unlike other treatment options, behavioral interventions can be delivered in various formats (eg, in-person, telehealth), are time-limited, and cause few (if any) undesirable systemic side effects.
Conclusions:
Behavioral intervention is an integral component of interprofessional care and key aspect of living well with MS.
... Research has shown that perceived stress has negative effects on the exacerbation and relapse rate of MS (Ackerman et al., 2002;Brown et al., 2006;Mitsonis et al., 2008) and can adversely affect the physical and psychological aspects of patients' lives (Salehpoor, Kafi, Rezaei, Hosseininezhad, & Salehi, 2012). Perceived stress impinges on the normal functioning of the hypothalamic-pituitary-adrenal axis through the release of the corticotropic hormone, which has a negative effect on the immune responses in patients with MS (Habib, Gold, & Chrousos, 2001). ...
Stress is a commonly reported concern of individuals with chronical diseases, including multiple sclerosis (MS). This study sought to investigate the relationships between self-transcendence, death anxiety, and perceived stress among individuals with MS from Iran. A second aim of the study was to assess the buffering effect of self-transcendence in the relationship between death anxiety and perceived stress. Two hundred and fifteen participants with MS from four hospitals completed measures assessing self-transcendence, death anxiety, and perceived stress. Using structural equation modeling, death anxiety was found to be positively related to perceived stress. In addition, there was a negative relationship between self-transcendence and perceived stress. Results of the study suggest that self-transcendence is a buffer in the link between death anxiety and perceived stress for individuals with MS. The findings demonstrate the importance of self-transcendence in decreasing the effects of death anxiety on perceived stress and have clinical implications for health professionals.
... Depression is common among MS patients; its life time risk has been estimated to be around 50% (Feinstein, 2011;Sadovnick et al., 1996;Minden and Schiffer, 1990). Because of its high prevalence, it might affect MS course (Mohr et al., 2000;Ackerman et al., 2000). In depressed patients without MS, lower vitamin D level is associated with higher depression scores and severity (Hoogendijk et al., 2008;Milaneschi et al., 2014;Milaneschi et al., 2010;Almeida et al., 2015). ...
Background:
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Depression is common among MS patients. In patients without MS, lower vitamin D levels were associated with higher depression scores and severity. Supplementation of vitamin D was associated with significant improvement of depressive symptoms.
Objective:
to evaluate the relation between vitamin D levels and depression scores, and the effect of vitamin D replacement on the depressive symptoms in patients with MS.
Methods:
The study included 35 patients with relapsing remitting multiple sclerosis. Neurological, psychiatric, and radiological evaluations were done. Participants received 10,000 IU of cholecalciferol daily for 12 months.
Results:
Vitamin D level was low at baseline. Depressive symptoms were high at baseline and improved with vitamin D replacement although, Expanded Disability Status Scale (EDSS) score was not improving. Vitamin D levels correlated negatively with depressive symptoms at baseline and follow up periods.
Conclusion:
Lower vitamin D levels are associated with higher depressive scores, and vitamin D replacement could improve depressive symptoms in patients with relapsing remitting multiple sclerosis.
... However, a long range of stimulatory substances and situations have been described, of which some seems to be relevant for MS as various stress situations (mental and physical) that has been reported as important factors for the stimulation of mast cells [39] [40]. This is relevant in the present context since mast cells may regulate blood-brain barrier [39], and that stress is a risk factor for multiple sclerosis [41] [42] Catestatin, (fragment of chromogranin-A, which is coreleased with hormones from the enteroendocrine system) is a potent releasing factor for mast cells [43] and may obviously be a part of stress-related stimulatory factors for mast cells. ...
... Dobroczynne działanie wysiłku fizycznego ma szczególnie ważne znaczenie w dzisiejszych czasach, kiedy coraz większa część populacji żyje coraz szybciej. To właśnie tempo życia może nasilać występowanie stresu [1], na który człowiek reaguje przede wszystkim na poziomie fizjologicznym. W sytuacji stresowej w organizmie dochodzi do zmian wskazujących na ogólną mobilizację zasobów energetycznych. ...
STRESZCZENIEWstęp: Słowo joga (Goya) pochodzi od sanskryckiego yij i oznacza: wiązać, łączyć, przywiązywać i skupiać na czymś uwagę. Oznacza także połączenie oraz zjednoczenie. System jogi zebrał i usystematyzował Patańdżali w swojej pracy „Yoga Sittrach”. Joga ma za zadanie ukształtowanie właściwej kultury fizycznej i duchowej (umysł) bez względu na poglądy religijne, pochodzenie oraz przynależność do grupy społecznej. Celem pracy była ocena zależności pomiędzy regularnym trenowaniem jogi a strategią radzenia sobie ze stresem, wartościami ciśnienia tętniczego i występowaniem otyłości brzusznej. Materiał i metody: W badaniach wzięło udział 100 osób podzielonych na 2 grupy. Pierwsza to regularnie trenujący jogę uczniowie szkoły jogi. Druga to spontanicznie wybrane osoby nieuprawiające regularnie żadnego sportu. Badani byli w wieku 18–60 lat. Do uzyskania materiału badawczego użyto kwestionariusz ankiety własnego autorstwa oraz test mini-COPE. Ponadto wykonano badanie ciśnienia tętniczego krwi i obwodu pasa w celu oceny występowania otyłości brzusznej. Wyniki: Wśród osób trenujących jogę zauważono średni mniejszy obwód talii u kobiet 82,8 ±8 w stosunku do mężczyzn 90,3 ±11 (p = 0,034). Prawidłowy obwód w pasie wykazano u 43 (86%) osób trenujących jogę oraz u 34 (68%) osób z grupy kontrolnej. Wskaźnik masy ciała (BMI) również wypadł na korzyść osób trenujących jogę, które przeważały liczebnie o 15 (30%) osób w kategorii BMI w normie. Otyłość centralną i BMI wskazujące na otyłość w grupie jogi wykazano u 10 (20%) osób, a w grupie kontrolnej u 15 (30%) osób. W badaniach autorskich nie stwierdzono istotnej różnicy w średnim ciśnieniu badanych grup. Wnioski: Na podstawie analizy kwestionariusza mini-COPE osoby regularnie trenujące jogę wybierają bardziej efektywne strategie radzenia sobie ze stresem. Regularne uprawianie jogi jest czynnikiem zmniejszającym otyłość brzuszną. Mężczyźni trenujący jogę mają wartości ciśnienia tętniczego niższe niż osoby nieuprawiające żadnego sportu.
... 6,7 MS patients often seek out mind-body therapies, and studies indicate benefits including improved quality of life and physical functioning and moderation of common MS symptoms such as fatigue. 6,[8][9][10][11][12] Recent reviews focusing on potential benefits of mindfulness meditation, for example, suggest an association between meditation practice and lower risk of depression and improved quality of life in people with MS. 9,[13][14][15] Given known associations between measures of MS disease activity and stressful life events, and the moderating effect of stress management programs on these measures of disease activity, 16,17 it is been postulated that integrative therapies mediate benefits through the reduction of autonomic arousal and stress. 18,19 Among integrative modalities, Guided Imagery (GI) is considered a "relaxation modality" by the National Center for Complementary and Integrative Health, because it can profoundly activate the body's natural relaxation response as characterized by slower breathing and lower blood pressure as well as increased feelings of well-being. ...
Multiple sclerosis is a disabling and progressive neurological disease that has significant negative effects on health-related quality of life. This exploratory efficacy study examined the effects of Healing Light Guided Imagery (HLGI), a novel variant of guided imagery, compared with a wait-list control in patients with relapsing-remitting multiple sclerosis. Changes in the Beck Depression Inventory, Fatigue Severity Scale, and Multiple Sclerosis Quality of Life instrument (physical and mental components) were compared between groups. Patients who completed HLGI (N = 9) showed significant reductions in depressed mood ( P < .05) and fatigue ( P < .01) and showed significant gains in physical ( P = .01) and mental ( P < .01) quality of life compared with journaling (N = 8). Our results suggest that HLGI can improve self-reported physical and mental well-being in patients with relapsing-remitting multiple sclerosis. Further research is needed to study the effectiveness of this therapy, as well as its mind-body mechanisms of action.
... The causal factors contributing to onset and severity of MS are not well understood; however, stress was suggested to modulate the inflammatory processes and symptoms of this disease (Huitinga et al., 2004;Heesen et al., 2007 b). Patients afflicted by MS frequently report that stress triggers relapses and exacerbates the clinical symptoms (Ackerman et al., 2002;Buljevac et al., 2003;Heesen et al., 2007a). Furthermore, psychological stress may exacerbate the course of relapsing-remitting MS (Karagkouni et al., 2013) and cause new lesions in the brain of MS patients (Mohr et al., 2004;Gold et al., 2005). ...
The causal factors determining the onset and severity of multiple sclerosis (MS) are not well understood. Here, we investigated the influence of chronic stress on clinical symptoms, metabolic and epigenetic manifestations of experimental autoimmune encephalomyelitis (EAE), a common animal model of MS. Lewis rats were immunized for monophasic EAE with MBP69-88 and were exposed to chronic stress for 37 days starting 7 days prior to immunization. The exposure to stress accelerated and exacerbated the clinical symptoms of EAE. At the peak of EAE symptoms and during recovery, stress altered mechanical allodynia. Both stress and EAE also disrupted metabolic status as indicated by trace elemental analysis in body hair. Stress particularly exacerbated chlorine and vanadium deposition in EAE animals. Moreover, deep sequencing revealed a considerable impact of stress on microRNA expression in EAE. EAE by itself upregulated microRNA expression in lumbar spinal cord, including miR-16, miR-21, miR-142-3p, miR-142-5p, miR-146a, and miR-155. Stress in EAE up-regulated miR-16, miR-146a and miR-155 levels. The latter two microRNAs are recognized biomarkers of human MS. Thus, stress may synergistically exacerbate severity of EAE by altering epigenetic regulatory pathways. The findings suggest that stress may represent a significant risk factor for symptomatic deterioration in MS. Stress-related metabolic and microRNA signatures support their value as biomarkers for predicting the risk and severity of MS.
... Since demoralization syndrome is consist of emotional, cognitive and behavioral components, it seems that any intervention to decreasing its symptoms should cover cognitive components which are effective on forming new thoughts and meaning. Preoccupations about disease, fear of death, concern about disability and future, are the most dominance concerns of patients which should be considered (1,3,14). Previous studies show that several psychological interventions are implemented to meet patients' depression, anxiety, distress, and etc., including logo therapy (15), insight-oriented group therapy (16), cognitive behavioral therapy (17,18), program to reducing stress, cognitive rehabilitation (19). ...
Objectives: Multiple Sclerosis is the most prevalent central nervous system diseases thatdue to being chronic, frequent recurrence, uncertainty about its progress, and disability, can lead to various distresses as well as demoralization . Rehabilitation method based on Cognitive-Existential therapy is an integratedapproach which can help to decrease demoralization syndrome in these patients. This study aimed to exploring effectiveness of rehabilitation method based on Cognitive-Existential approach on decreasing demoralization syndrome in patients with MS.
Methods: Single subject design is used in this study. Among women who had referred to Tehran MS Association, 3 women (aged between 20-40) were selected through purposeful sampling and separately participated in 10 sessions (90 minutes). Participants were assessed during 7 phases of intervention (2 baselines, 3 measurement during intervention, 2 follow-up) through Demoralization Syndrome Scale (2004) and Cognitive Distortion scale (2010). Data were analyzed by calculating process variation index and visual analysis.
Results: Comparing patients with MS scores on the diagram during 7 time measurement and calculating recovery percentage, represent decreasing in demoralization syndrome score scale.
Discussions: Findings showed that rehabilitation method based on Cognitive Existential approach can decrease demoralization syndrome in patients with MS.
... The results of some of the studies state that stress, anxiety and depression symptoms in the multiple sclerosis patients have a close association with disease relapse and life quality reduction (6)(7)(8) . In an assessment, Schreurs et al. reported that the physical fatigue has a correlation with the physical inability and mental fatigue with depression in these patients, in a manner that the physical fatigue is a predictor of physical inability in the next one year (9) . ...
Introduction: Fatigue is one of the most important symptoms of multiple sclerosis where in majority of patients that often suffer from it are young individuals in active life stage. This study was carried out with an aim to assess the effectiveness of psychological Training with gradual muscle relaxation technique on fatigue in multiple sclerosis patients. Material and methods: In this triple blind placebo-controlled clinical trial study, 60 multiple sclerosis patients that were Multiple Sclerosis Association Members of Yazd Province via an easy sampling method and considering the input and output criteria entered the study. The samples were randomly divided into two groups of test (30 persons) and control (30 persons) respectively, and test group received 12 sessions of psychological education with gradual muscle relaxation technique, two sessions a week, whereas for control group nil intervention were adopted. The information was collected using a demographic questionnaire and the Fatigue Severity Scale (FSS). Prior to intervention, immediately and three months after an intervention. For analysis of information the statistical tests; Pearson correlation, Repeated measures and t-student was used. Results: Considering that the patients were randomly divided into two groups of test and control, prior to education did not exhibit a statistical difference in the demographic characteristics, disease duration, body mass index, fatigue scale of patients. (P>0.05). The fatigue scale in the test and control groups prior to the intervention were 41.9 +/- 6.666 and 42.833 +/- 8.363, respectively, immediately after the intervention were 41 +/- 6.103 and 33.9 +/- 7.073, respectively, and three months after an intervention were 41.1 +/- 6.567 and 35.567 +/- 7.61, respectively and this difference from statistical viewpoint was significant (P<0.001). Likewise, the Repeated measures statistical test showed a significant reduction in the Fatigue Severity Scale in the education group in triple measurements (P<0.00001). Conclusion: The psychological Training with gradual muscle relaxation technique in the multiple sclerosis patients can lead to reduction of fatigue scale. Therefore, this method can be safely suggested as an effective and affordable in terms of cost and time for multiple sclerosis patients.
... In contrast, there is a stronger association between stressful life events and disease progression. Acute life stressors have been shown to be correlated with relapses in MS (Ackerman et al. 2002 ;Mei-Tal et al. 1970 ;Yamout et al. 2010 ). Moreover, a recent prospective study indicated that MS patients that experience three or more stressful life events within a 4-week timeframe were associated with a fi vefold increase in exacerbation risk (Mitsonis et al. 2008 ). ...
The nervous system, endocrine system, and immune system are highly connected and affect the outcome of viral infections. This chapter introduces a brief history of the field of psychoneuroimmunology and then provides examples of the impact of stress on two neurotropic viral infections: herpes simplex and Theiler’s virus.
Psychological stress has been implicated in the development and progression of multiple sclerosis (MS), and one of the best models for studying the pathogenesis of MS is Theiler’s virus infection in mice. Three stress paradigms were investigated in Theiler’s virus infection: restraint stress, social stress, and maternal separation stress. Generally these stressors were shown to decrease both the innate and adaptive immune response following Theiler’s virus infection through the increased production of glucocorticoids. The stress-induced immunosuppression results in increased viral titers in the central nervous system and increased inflammatory demyelination. In conclusion, stress at the time of infection with a neurotropic virus results in decreased immune response to the virus and increased viral replication in the CNS, which in turn leads to more severe chronic inflammatory disease.
... Psychological stress has been shown to precede both the onset and recurrence of chronic MS symptochronic MS in 70-80% of cases, using standardized assessment of life stressors measures [13]. More recently, stressful life events have been shown to predict the development of new lesions and relapses in chronic MS [14]. Metaanalyses concerning stress and chronic MS h a v e concluded that there was a significantly increased risk of exacerbation associated with stressful life events [15,16]. ...
Background:
Multiple sclerosis (MS) is characterized by a significant deterioration in auditory and visual reaction times along with associated depression and anxiety. Yoga and Physical therapy (PT) interventions have been found to enhance recovery from these problems in various neuropsychiatric illnesses, but sufficient evidence is lacking in chronic MS population. The aim of this study was to assess the effect of integrated Yoga and Physical therapy (IYP) on audiovisual reaction times, depression and anxiety in patients suffering from chronic MS.
Methods:
From a neuro-rehabilitation center in Germany, 11 patients (six females) suffering from MS for 19±7.4 years were recruited. Subjects were in the age range of 55.45±10.02 years and had Extended Disability Status Scores (EDSS) below 7. All the subjects received mind-body intervention of integrated Yoga and Physical therapy (IYP) for 3 weeks. The intervention was given in a residential setup. Patients followed a routine involving Yogic physical postures, pranayama, and meditations along with various Physical therapy (PT) techniques for 21 days, 5 days a week, 5 h/day. They were assessed before and after intervention for changes in audiovisual reaction times (using Brain Fit Model No. OT 400), anxiety, and depression [using Hospital Anxiety and Depression Scale (HADS)]. Data was analyzed using paired samples test.
Results:
There was significant improvement in visual reaction time (p=0.01), depression (p=0.04), and anxiety (p=0.02) scores at the end of 3 weeks as compared to the baseline. Auditory reaction time showed reduction with borderline statistical significance (p=0.058).
Conclusions:
This pilot project suggests utility of IYP intervention for improving audiovisual reaction times and psychological health in chronic MS patients. In future, randomized controlled trials with larger sample size should be performed to confirm these findings.
... A decrease in perceived fatigue could lead to improvement in multiple aspects of life in these individuals allowing them increased participation in life activities due to increased energy. Like fatigue, stress is an important issue for people with MS since studies have shown a connection between moderate life stress and exacerbation [24,51]. Daily physiologic stress was measured by HR and BP during the meditation class. ...
... Since demoralization syndrome is consist of emotional, cognitive and behavioral components, it seems that any intervention to decreasing its symptoms should cover cognitive components which are effective on forming new thoughts and meaning. Preoccupations about disease, fear of death, concern about disability and future, are the most dominance concerns of patients which should be considered (1,3,14). Previous studies show that several psychological interventions are implemented to meet patients' depression, anxiety, distress, and etc., including logo therapy (15), insight-oriented group therapy (16), cognitive behavioral therapy (17,18), program to reducing stress, cognitive rehabilitation (19). ...
Objectives: Multiple Sclerosis (MS) is the most prevalent central nervous system diseases that due to chronicity, frequent recurrence, uncertainty about progression, and disability, can lead to various distresses as well as demoralization. Rehabilitation method based on Cognitive-Existential therapy is an integrated approach to decreasing demoralization syndrome in these patients. This study aimed to exploring effectiveness of rehabilitation method based on Cognitive-Existential approach on decreasing demoralization syndrome in patients with Multiple Sclerosis. Methods: Single subject design was used in this study. Among women who had referred to Tehran MS Association, 3 women (aged between 20-40) were selected through purposeful sampling and separately participated in 10 sessions (90 minutes). Participants were assessed during 7 phases of intervention (2 baselines, 3 measurements during intervention, 2 follow-up) through Demoralization Syndrome Scale and Cognitive Distortion scale. Data were analyzed by calculating process variation index and visual analysis. Results: Comparing patients with MS scores on the diagram during 7 time measurement and calculating recovery percentage, represent decreasing in demoralization syndrome score scale. Discussion: Findings showed that rehabilitation method based on Cognitive Existential approach can decrease demoralization syndrome in patients with MS.
... Another environmental factor that may contribute to both the onset and exacerbation of MS is psychological stress (Ackerman et al., 2003;Mohr et al., 2004). Stress, acting through the hypothalamic-pituitary-adrenal (HPA) axis as well as the autonomic nervous system, has been shown to modulate immune responses, with acute stress stimulating leukocyte trafficking and chronic stress being immunosuppressive (Dhabhar and McEwen, 1997). ...
... Los eventos vitales incluyen acontecimientos de naturaleza aparentemente positiva (e.g., la promoción en el trabajo), negativa (e.g., la muerte del cónyuge) o neutra (e.g., un cambio de casa). Independientemente de la naturaleza positiva, negativa o neutra de los eventos vitales, se ha documentado que son acontecimientos estresantes que causan malestar y que están relacionados con la propensión de una persona para adquirir o para que se agrave una enfermedad (e.g., Ackerman et al., 2002) y con otra clase de problemas como una disminución de la habilidad para ejecutar una tarea (e.g., Vondras, Powless, Olson, Wheeler, & Snudden, 2005) o con la falta de sueño (e.g., Specchio et al., 2004), entre otras cosas. ...
Social support buffers the noxious effects of stress, but the effect of increasing the number of perceived helpers is not known. The purpose was to determine if the relation between increasing the number of perceived helpers and the discomfort produced by stressful life events could be described by a power function, as predicted by social impact theory. The second purpose was to determine if the exponents of the functions varied according to the severity of the events and to the socio-demographic characteristics of the 739 adult participants. The discomfort of life stress was a negatively-accelerated decreasing function of the number of helpers. The steepness of the decrease varied according to the severity of the situations. For a serious event the decrease was smaller than for a not-so-serious event, and for intermediate stressful situations, the decrease was correspondingly intermediate. The addition of helpers decreased the discomfort of life stress more rapidly for women, for married people, as age increased and as educational and socioeconomic levels decreased. It was concluded that the beneficial effects of social support depend on perceiving help from a relatively small number of persons.
... At the same time, while chronic stressrelated effects upon the immune system are uniformly deleterious, acute stress appears to have both protective and adverse effects. For example, acute stress can enhance the acquisition and expression of immunoprotection by activation of bodily defences prior to wounding or infection (Ackerman et al., 2002;Amkraut et al., 1971;Charney, 2004;Dhabhar, 2009), or alternatively induce immunopathology via exacerbating autoimmune inflammation, with respiratory and cardiovascular consequences (Al'Abadie et al., 1994;Black, 2006;Bosch et al., 2003;Dhabhar et al., 1995;Garg et al., 2001). The dissociation between excitatory and inhibitory molecular mechanisms remains incomplete. ...
In spite of advances in understanding the cross-talk between the peripheral immune system and the brain, the molecular mechanisms underlying the rapid adaptation of the immune system to an acute psychological stressor remain largely unknown. Conventional approaches to classify molecular factors mediating these responses have targeted relatively few biological measurements or explored cross-sectional study designs, and therefore have restricted characterization of stress-immune interactions. This exploratory study analyzed transcriptional profiles and flow cytometric data of peripheral blood leukocytes with physiological (endocrine, autonomic) measurements collected throughout the sequence of events leading up to, during, and after short-term exposure to physical danger in humans. Immediate immunomodulation to acute psychological stress was defined as a short-term selective up-regulation of Natural Killer (NK) cell-associated cytotoxic and IL-12 mediated signaling genes that correlated with increased cortisol, catecholamines and NK cells into the periphery. In parallel, we observed down-regulation of innate immune toll-like receptor genes and genes of the MyD88-dependent signaling pathway. Focusing analyses on discrete groups of coordinately expressed genes (modules) throughout the time-series revealed immune stress responses in modules associated to immune/defense response, response to wounding, cytokine production, TCR signaling and NK cell cytotoxicity which differed between males and females. These results offer a spring-board for future research towards improved treatment of stress-related disease including the impact of stress on cardiovascular and autoimmune disorders, and identifies an immune mechanism by which vulnerabilities to these diseases may be gender-specific.
... Similarly, cognitive impairments, such as memory deficits (Covey et al., 2011;Amato et al., 2001), are disruptive to daily living (Amato et al., 1995(Amato et al., , 2001Rao et al., 1991). In addition, periods of psychological stress have been associated with the development and exacerbation of symptoms of MS, including pain and cognitive impairments, which will be discussed in more detail below (Ackerman et al., 2002;Brown et al., 2005, 2006a, 2006b, Li et al., 2004Mohr et al., 2004;Sorenson et al., 2013). Animal models are needed to further our understanding of MS-related pain and cognitive impairments and their underlying mechanisms. ...
... The role of stress in MS was historically debated, but despite methodological differences across many studies, there is satisfactory evidence supporting the negative influence of stress in MS pathology [55]. Several studies have shown that stressful life events (SLEs) precede symptom onset in MS patients compared with population controls for the same prodromal time period, and SLEs also precede disease relapses and increased CNS lesions in MS patients [56][57][58][59][60][61][62][63][64]. There have also been a handful of studies that have investigated the relationship between SLEs in childhood and MS risk in adulthood. ...
Multiple sclerosis (MS) is a debilitating autoimmune disease with a prominent inflammatory component. There have been strides identifying genetic and environmental MS risk factors, though much of the disease risk remains unknown. Recent large observational studies suggest adverse socioeconomic position increases the risk for MS, however the mediating biological processes are not understood. We hypothesize a prominent role for stress response, both the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, which become maladaptive under frequent or chronic stimulation resulting in a proinflammatory phenotype. Thus, adverse SEP and chronic stress may predispose individuals for MS.
... Men tend to take a passive role in maintaining their health in this culture, being this pattern particularly common in males with low social status. Alternatively, the incidence of disease in men may be the result of the social disadvantaged environment and the unequal social justice for Two major etiological suppositions were behind the susceptibility to this disease and its exacerbations: a genetic predisposition and, on the other hand, environmental risk factors (Ackerman et al., 2002;Haines et al., 2003;Goldenberg, 2012). MS has some comorbidity with psychological disorders like conversion and mood disorders and, taken together, may cause cognitive impairment in about 45-65% of patients (American Psychiatric Association, 2004;Bobholz & Rao, 2003;Prakash, Snook, Lewis, Motl, & Kramer, 2008). ...
The purpose of this research was to examine the role of fatigue, depression and personality traits in males with and without multiple sclerosis (MS) and to investigate the influence of age and the numbers of years of education on these constructs. Participants were 30 males with MS and 30 males without MS who were selected following a sampling method from Shiraz City, Iran. The Fatigue Severity Scale (FSS), the Beck Depression Inventory (BDI), the NEO Personality Inventory-Revised (NEO PI-R) and a demographic questionnaire were applied. Resulting data showed that patients with MS had significantly higher fatigue, depression and neuroticism compared to control group. Resulting data showed that patients without MS had higher levels of extraversion, openness to experience, agreeableness and conscientiousness compared with patients with MS. There was no significant effect for age and the numbers of years of education on fatigue and depression, nor on the Big Five personality traits.
The immune system is known to be controlled by the autonomic nervous system including sympathetic and parasympathetic (vagus) nerves. C1 neurons in the medulla oblongata, which participate in the control of the autonomic nervous system, are responders to stressors and regulate the immune system. Short-term activation of C1 neurons suppresses inflammation, while the effect of a long-term activation of these neurons on the inflammatory reflex is unclear. We, herein, demonstrate that the coactivation of both the splenic sympathetic nerves and the adrenal gland adrenergic response are indispensable for the prognosis of acute lung injury. The chemogenetic activation of C1 neurons increased plasma catecholamine including adrenaline and noradrenaline levels. The deletion of catecholaminergic cells using local injections of viral vector in the adrenal gland abolished the protective effect against acute lung injury when the C1 neurons were stimulated by either chemogenetic or optogenetic tools. Furthermore, repeated activation of C1 neurons using chemogenetic tool inhibited the adrenal response without affecting the plasma noradrenaline levels, eliminated the protective effect against acute lung injury. This was rescued by the isoprenaline administration. We concluded that the maintenance of an adrenergic response via C1 neurons in the adrenal gland is a prerequisite for the delivery of an effective anti-inflammatory response.
Chapter 13 of ACSM's Resources for the Exercise Physiologist. Health Stress Management.
Au cours des vols spatiaux, les astronautes sont sujets à de nombreux stress perturbant leur organisme et notamment leur système immunitaire. Afin d’étudier ces altérations et du fait du nombre restreint de missions spatiales, il est nécessaire d’utiliser des modèles permettant de simuler, sur Terre, les stress rencontrés en vol. Au cours de cette thèse, nous avons étudié les effets de stress associés aux vols spatiaux sur le système du complément et les cellules dendritiques (DC). Dans un premier temps, nous avons étudié les effets d’une combinaison de stress ou de stress individuels, sur l’expression de la molécule C3 du complément chez l’amphibien et la souris. Nous avons montré que certains de ces stress associés aux vols spatiaux, dont la microgravité simulée, provoquent une augmentation de C3 dans des larves de P. waltl. Toutefois, ces variations ne sont pas retrouvées chez des souris placées en microgravité simulée par suspension anti-orthostatique. Dans un deuxième temps, nous avons étudié in vitro les effets d’une microgravité simulée (RPM) sur le phénotype et la fonction de DC murines. Nous avons montré que la structure du cytosquelette d’actine et la survie des DC étaient altérées par la microgravité simulée. De plus, les DC exposées à la RPM présentent un phénotype plus immature caractérisé à la fois par une diminution de l’expression membranaire des molécules de co-stimulation mais également de leur capacité à sécréter des cytokines pro-inflammatoires. Bien que ces caractéristiques soient indispensables aux fonctions des DC, les modifications mises en évidence ne semblent toutefois pas altérer leur capacité à présenter l’antigène. Pris ensemble, ces résultats montrent l’importance d’étudier les effets de stress associés aux vols spatiaux, comme la microgravité, sur le système immunitaire. Une meilleure compréhension des mécanismes mis en jeu permettra de comprendre les effets du stress sur la santé et de développer des contremesures adaptées aux vols spatiaux.
Introduction: Multiple Sclerosis (MS) is the most common illness causing neurological inabilities in young adults. The ability of the ill person to use coping skills is an important factor that could help reduce stress and manage the increasing challenges caused by this debilitating illness. The present study focused on comparing the amount of coping skills used by MS sufferers, who were or were not members of a peer support group. Methods: The method of the study was descriptive-analytical. The study was conducted at the Multiple Sclerosis Society of Zanjan City during year 2016. Simple random sampling without replacement was conducted on 30 MS sufferers, who were members and 90, who were not members of the peer support group. The data gathering tool included a demographic questionnaire and Jalowiec coping skills questionnaire. Fisher's exact test and t-test were used to analyze the data. Results: Comparison of the amounts of coping skills used by member and non-member patients in the peer support group revealed that they differed insignificantly (0.735) in terms of excitement-oriented skills, and significantly in terms of problem-oriented coping skills. Furthermore, the member patients used more problem-oriented coping skills than the non-member patients (0.009). Conclusions: Peer support has an increasing effect on the use of problem-oriented coping skills. Thus, it will be helpful to encourage patients to become a member of the peer support group.
Introduction: Multiple Sclerosis (MS) is the most common illness causing neurological inabilities in young adults. The ability of the ill person to use coping skills is an important factor that could help reduce stress and manage the increasing challenges caused by this debilitating illness. The present study focused on comparing the amount of coping skills used by MS sufferers, who were or were not members of a peer support group. Methods: The method of the study was descriptive-analytical. The study was conducted at the Multiple Sclerosis Society of Zanjan City during year 2016. Simple random sampling without replacement was conducted on 30 MS sufferers, who were members and 90, who were not members of the peer support group. The data gathering tool included a demographic questionnaire and Jalowiec coping skills questionnaire. Fisher's exact test and t-test were used to analyze the data. Results: Comparison of the amounts of coping skills used by member and non-member patients in the peer support group revealed that they differed insignificantly (0.735) in terms of excitement-oriented skills, and significantly in terms of problem-oriented coping skills. Furthermore, the member patients used more problem-oriented coping skills than the non-member patients (0.009). Conclusions: Peer support has an increasing effect on the use of problem-oriented coping skills. Thus, it will be helpful to encourage patients to become a member of the peer support group.
Emotional stress leads to the development of peripheral disorders and is recognized as a modifiable risk factor for psychiatric disorders, particularly depression and anxiety. However, not all individuals develop the negative consequences of emotional stress due to different stress coping strategies and resilience to stressful stimuli. In this review, we discuss individual differences in coping styles and the potential mechanisms that contribute to individual vulnerability to stress, such as parameters of the immune system and oxidative state. Initial differences in inflammatory and oxidative processes determine resistance to stress and stress-related disorders via the alteration of neurotransmitter content in the brain and biological fluids. Differences in coping styles may serve as possible predictors of resistance to stress and stress-related disorders, even before stressful conditions. The investigation of natural variabilities in stress resilience may allow the development of new methods for preventive medicine and the personalized treatment of stress-related conditions.
Our group has proposed that in contrast to chronic stress that can have harmful effects, the short-term (fight-or-flight) stress response (lasting for minutes to hours) is nature's fundamental survival mechanism that enhances protection and performance under conditions involving threat/challenge/opportunity. Short-term stress enhances innate/primary, adaptive/secondary, vaccine-induced, and anti-tumor immune responses, and post-surgical recovery. Mechanisms and mediators include stress hormones, dendritic cell, neutrophil, macrophage, and lymphocyte trafficking/function and local/systemic chemokine and cytokine production. Short-term stress may also enhance mental/cognitive and physical performance through effects on brain, musculo-skeletal, and cardiovascular function, reappraisal of threat/anxiety, and training-induced stress-optimization. Therefore, short-term stress psychology/physiology could be harnessed to enhance immuno-protection, as well as mental and physical performance. This review aims to provide a conceptual framework and targets for further investigation of mechanisms and conditions under which the protective/adaptive aspects of short-term stress/exercise can be optimized/harnessed, and for developing pharmacological/biobehavioral interventions to enhance health/healing, and mental/cognitive/physical performance.
Introduction:
The word yoga (Goya) is derived from the Sanskrit yii and means: bind, connect, attach and focus attention on something. It also means connection, and the union. The system of yoga has collected and systematized Patanjali in his “Yoga Sittrach” work. Yoga has the task of shaping proper physical culture and spirit (mind), regardless of religious beliefs, national origin, membership in a social group. The aim of the study was to evaluate the relationship between yoga and regular coaching strategy for coping with stress, blood pressure and abdominal obesity.
Material and methods:
The study involved 100 people divided into 2 groups. The first group comprised students regularly practicing yoga. The second group were randomly selected subjects not regularly engaged in sport. The age of the subjects ranged 18–60 years and over. Research material was gathered using a questionnaire designed by the authors, and the mini -COPE test. In addition, blood pressure and waist circumference were measured to assess the prevalence of abdominal obesity.
Results:
Among people who practice yoga the average waist circumference was 82.8 ±8 in women and 90.3 ±11 in men (p < 0.034). A healthy waistline was found in 43 (86%)subjects in the yoga group, and 34 (68%) subjects in the control group. Body mass index (BMI) also falls in favour of yoga, and in this group 15 (30%) more subjects had normal BMI. Abdominal obesity and BMI indicating obesity was found in 10 (20%) subjects from the yoga group and 15 (30%) from the control group. The study revealed no significant differences in mean blood pressure between the analysed groups.
Conclusions:
Based on the analysis of the questionnaire mini-COPE people regularly Training Yoga choose more effective strategies for coping with stress. Regular practice of yoga is a factor in reducing abdominal obesity. Men who trains yoga have blood pressure lower than those who doesn’t practice any sport.
MS-pathogenesis involves both genetic-susceptibility and environmental determinants. Three (or more) sequential environmental-factors are implicated. The first acts near birth, the second acts during childhood/adolescence, and the third acts subsequently. Two candidate factors (vitamin D deficiency and Epstein-Barr viral infection) seem particularly well-suited to the first two environmental-events but other factors (e.g., obesity and smoking behavior) seem also to be involved in the causal scheme.
Multiple sclerosis is a disease of the central nervous system that cause major psychological challenging in the patient all over the world. In this case, psychological interventions can be useful this study was aimed to predictor factors of adherence to treatment in patient with multiple sclerosis. This was on descriptive study with questionnaire. One hundred - twenty patients were selected through accessible sampling method from MS society of Tehran. They completed all administered demographic questionnaire, Multiple Sclerosis Treatment Adherence Questionnaire (MSTAQ), General Self efficacy (GSE), NEO five factor inventory (NEO-FFI), Beck Depression Inventory (BDI), Short Form health survey questionnaire (SF-36), Kattle Anxiety Inventory (KAI), Positive And Negative Affect Scales (PANAS), Philips Social Support Questionnaire (SSQ) and Feedback. Data was analyzed using MONOVA repeated measure design, descriminent analysis and logistic regression. The finding of this study indicated that there is a significant difference in adherence in Multiple Sclerosis with depression, neuroticism, entroversion, conscientiousness, quality of life, family social support and anxiety (a=0/05). The Results show that adherence has direct relationship with psychological factors. Better treatment for this patient in addition to medication should also be psychological counseling. This method can reduce anxiety and depression and increase self efficacy and improve quality of life.
Multiple sclerosis is an inflammatory disease of the brain, with coexisting abnormalities in steroid control and in the sympathetic nervous system. The animal model of MS, EAE, is easily suppressed by steroids. Immunity is also altered by steroids. Nonetheless, there is no solid evidence that stress affects the course of MS.
Psychological stress can have bidirectional effects on immune function, being immunosuppressive under certain conditions but immunoenhancing under others.
Chronic stress (lasting for weeks, months, or years) is known to suppress or dysregulate immune function.
Acute stress (lasting for minutes to hours) has been shown to enhance immune function, particularly in the skin.
Acute stress experienced at the time of immune activation or antigen exposure significantly enhances primary/innate or secondary/adaptive immune responses.
Acute stress induces a redistribution of leukocytes from the blood to compartments like the skin and sentinel lymph nodes, and this redistribution is thought to be one important mediator of the immunoenhancing effects of acute stress.
The studies described here may provide substrates for interventions that could be designed to ameliorate stress-induced exacerbation of allergic, inflammatory, or auto-immune diseases.
These studies also provide the framework for developing therapeutic interventions that may harness the body’s endogenous adjuvant-like immunoenhancing mechanisms to enhance protective immunity during vaccination, infection, or wound healing.
This article gives an overview of research on the correlation between the course of multiple sclerosis (MS) disease and stress. It also discusses the most frequently verified hypotheses and methodological difficulties that researchers must face. Results presented here indicate that the relationship between MS and stress is very complex and is dependent on a variety of biological and psychological factors. Importance of the following aspects is considered: the prevalence and intensity of stressful events, strategies to cope with stress, personality, viral infections, cardiovascular and immunological systems activity and neurodegenerative processes. The reciprocal relation between stress and MS is also analyzed. Recent hypotheses focus on the impact of stress on changes in endocrine and immunological systems and their role in the dynamics of the disease. The foundations of such reasoning are the results of studies on the effects of stress on the immune system via the hypothalamic- pituitary-adrenal axis (HPA) and autonomic nervous system. Although there are a number of hypotheses about the activity of the HPA in the course of MS, we still do not know whether it is conducive to progression of the disease or it is the consequence of neurodegenerative processes. All the knowledge gathered so far gives no grounds for an unequivocal conclusion on how stress influences the biological response and the worsening of the disease associated with it. In spite of their ambiguity, the results of previous studies encourage specific therapeutic interventions, examples of which the reader will find in this article.
Information was obtained on stressful life circumstances, using the Life Events and Difficulties Schedule (LEDS) from 39 patients with early multiple sclerosis and 40 matched nonpatient volunteers. The proportion of multiple sclerosis patients who experienced marked life adversity in the year prior to onset of symptoms was significantly higher than for nonpatients in the year before interview (77% vs. 35%). The excess in marked life stress was most evident in the 6 months before onset. Such stressors might explain the timing of symptom exacerbation for some patients with multiple sclerosis, perhaps by perturbing an already unstable neuroimmunological system.
To examine the relationship between stressful life events and psychological distress, and the subsequent development of gadolinium-enhancing (Gd+) brain lesions.
It has long been speculated that stressful life events and psychological distress are associated with disease exacerbation in MS. This is the first prospective longitudinal study of the relationship between stressful life events, psychological distress, and disease activity as measured by Gd+ brain MRI.
Thirty-six patients (mean age, 44.4 years; 22 women, 14 men) with relapsing forms of MS were assessed once every 4 weeks for 28 to 100 weeks. Assessments included Gd+ MRI, the Social Readjustment Rating Scale (SRRS), the Hassles Scale, and the Profile of Mood States. The SRRS was altered in the following manner: 1) three items that confounded with MS were eliminated, 2) endorsed items were rated for intensity, and 3) the scale was divided into three subscales: major negative events, conflict and disruption in routine, and positive life events. Data were analyzed using mixed-effects logistic regression to account for intrasubject correlations. Stress and distress measures were used to predict concurrent and future MRI activity.
For the total sample of patients, increased conflict and disruption in routine was followed by increased odds of developing new Gd+ brain lesions 8 weeks later (odds ratio, 1.64; p = 0.00083). There was no strong evidence of a relationship between psychological stress or distress and clinical exacerbation.
These data provide support for the notion that conflict and disruption in routine are related to subsequent disease activity in MS. However, this relationship is not sufficiently robust to predict clinical exacerbations reliably in individual patients.
One of the oldest controversies in multiple sclerosis (MS) research concerns the extent to which stressful life events alter the course and severity of illness. Numerous descriptive and case-control studies have suggested a relatively strong impact of stress on the onset and exacerbation of MS symptoms, yet the magnitude and even the direction of this effect varies between studies. This discrepancy may be due to a number of factors including difficulties in interpreting self-report data, lack of adequate controls, and variation in the type, intensity and duration of stressors under examination. This review summarizes the current literature on stress and MS disease activity, and offers a model of mediating and moderating factors that contribute to stress-induced MS exacerbations.
The relationship of stressful life events (SLEs) to acute exacerbations of multiple sclerosis (MS) was prospectively studied in 55 consecutive patients with a relapsing-remitting disease course. The quantity and quality of SLEs were determined by the Psychiatric Epidemiology Research Interview (PERI-M) administered at 4-month intervals. Exacerbating cases (n = 20) did not experience a greater number of SLEs than nonexacerbating controls (n = 35); however, patients who experienced qualitatively extreme events were 3.7 times as likely to exacerbate as those not exposed to such events. The quality rather than the quantity of SLEs was associated with acute exacerbations of MS.
Given the high rates of maladjustment among children of depressed mothers, parenting is likely to cause significant life stress in this population, potentially worsening the course of mothers’ depression. The present study is a comparison of severe life stress in 38 mothers and 62 non-mothers receiving treatment for recurrent major depression. Life stress was assessed using the Life Events and Difficulties Schedule [Brown and Harris, 1978a]. We hypothesized that mothers would evidence a greater number of severe life events and marked difficulties both in the year prior to the onset of their depressive index episode and in the time period following the onset of their current depressive episode. Prior to depression onset, mothers reported a significantly greater number of entrapping difficulties, but not marked difficulties, severe events, entrapping events, or humiliating events. However, following the onset of depression, mothers experienced a significantly greater number of severe events, entrapping events, marked difficulties, and entrapping difficulties, but not humiliating events. Mothers’ elevated levels of stress were attributable to child-related stress, predominantly related to children’s psychological and behavioral problems. Our findings suggest that comprehensive treatment for mothers with major depression needs to address their parenting style and any psychological problems experienced by their children. Depression and Anxiety 13:109–117, 2001. © 2001 Wiley-Liss, Inc.
This paper challenges several arguments for rejecting the rationale of Holmes' and Rahe's Social Readjustment Rating Scale and proposes procedural improvements for three aspects of life-event scale construction: construction of a life-event list, selection of judges, and tests of whether judges agree on their ratings. The proposed procedures are illustrated with the Psychiatric Epidemiology Research Interview (PERI) Life Events Scale. This list of 102 events was developed on the basis of surveys of events actually experienced in various populations. Ratings of the amount of change entailed in these events were collected from a community probability sample. Analysis of these ratings suggests that there are group differences, with more of these differences being due to ethnic background than to sex or social class.
During an eight year period 170 multiple sclerosis (MS) patients and 134 controls without physical impairment were followed closely to record all episodes of physical trauma and to measure their effect on exacerbation rate and progression of MS. There was a total of 1407 instances of trauma, which were sorted into various categories. Overall there was no significant correlation between all-traumas and disease activity. There was, however, a statistically significant negative correlation between traumatic episodes and exacerbations in 95 patients who had exacerbations during the programme, due primarily to less activity of the disease during a three month period following surgical procedures and fractures. Electrical injury had a significant positive association with exacerbation using a three month at-risk period, but there were no other significant positive correlations in any other category of trauma, including minor head injuries; there were no cases of head injury with prolonged unconsciousness. There was no linkage between the frequency of trauma and progression of disability. MS patients had two to three times more trauma than controls.
One method of evaluating the degree of neurologic impairment in MS has been the combination of grades (0 = normal to 5 or 6 = maximal impairment) within 8 Functional Systems (FS) and an overall Disability Status Scale (DSS) that had steps from 0 (normal) to 10 (death due to MS). A new Expanded Disability Status Scale (EDSS) is presented, with each of the former steps (1,2,3 . . . 9) now divided into two (1.0, 1.5, 2.0 . . . 9.5). The lower portion is obligatorily defined by Functional System grades. The FS are Pyramidal, Cerebellar, Brain Stem, Sensory, Bowel & Bladder, Visual, Cerebral, and Other; the Sensory and Bowel & Bladder Systems have been revised. Patterns of FS and relations of FS by type and grade to the DSS are demonstrated.
One hundred multiple sclerosis (MS) patients were compared to hospital controls, for life stress prior to onset age in the MS patients and controls did not differ on: the happiness of their childhood environment; their pre-onset age reaction to life's problems (relaxed and taking things in stride/tense or easily upset); or on their tendency to seek professional help with an emotional problem. However significantly more MS patients than controls reported that they were under unusual stress in the 2 yr period prior to onset age; and the MS patients described a greater number of stressful life situations, or single events, than the controls.
This study focuses on a sample of 35 patients who had recently suffered an attack of multiple sclerosis. They were first subjected to the so-called life stress method in order to look for a connection between life stresses and the attacks of multiple sclerosis. The sample was compared with a paired control population composed of patients recruited from admission departments and medical emergency departments. The AMDP psychopathological evaluation method was applied to the sample, to establish a characteristic mental profile of these patients. Three types of results are highlighted. First, the comparison of the event scores shows a significant difference between the population of patients suffering from an outbreak of multiple sclerosis and the control population. A connection between "life stresses" and the triggering of the outbreaks of multiple sclerosis is therefore mentioned and discussed. Second, the application of the system of the Association de méthodologie et de documentation psychiatrique brings out a mental profile common to patients suffering from multiple sclerosis, consisting of a very specific association of mood disorders: dysphoria, euphoria and mania on the one hand, and depression, anxiety and dramatization on the other, with relative anosognosia. The correlation between dysphoria, the syndrome's principal characteristic, and the event score adds another argument in favour of the connection between life stresses and the evolution of the disease. The main components of this mental profile are primarily correlated with the existence of a neuropsychology suggestive of a medial basal frontal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
Verdier-Taillefer M-H (INSERM U 360, Recherches épidémiologiques en neurologie et psychopathologie, 16 Avenue P Vaillant-Couturier, 94807 Villejuif Cedex France), Roullet E, Cesaro P and Alpérovitch A. Validation of self-reported disability in multiple sclerosis. International Journal of Epidemiology 1994; 23: 148–154.
In all 129 unselected patients with multiple sclerosis (MS) completed a 25 item auto-questionnaire for assessment of disability. Each patient was examined on the same day by a neurologist who was blind to patients' answers and gave Expanded Disability Status Scale (EDSS) scores. From the auto-questionnaire, eight scores were obtained, one for each of the seven functional systems rated by the EDSS and the eighth relating to walking difficulties. Analysis showed that correlation between patients' self assessments and the neurologist's ratings was high (r>0.50) for five out of the eight scores and low for three, especially for brainstem and mental functions which were excluded from subsequent analysis. Using a linear regression model, it was possible to predict the EDSS scores given by the neurologist (±1 point) from patients' answers in 73% of the cases. The performance of the model was robust and was not influenced by patients' characteristics (sex, age, disease course). This study shows that most aspects of MS disability can be self-assessed by patients, and suggest a useful approach when it is not feasible to examine each MS patient as in large community-based studies. Collaborative studies for defining and validating auto-questionnaires on disability should be encouraged.
We prospectively evaluated the relationship between a common psychological stressor and relapses in multiple sclerosis (MS) in a group of 32 MS patients exposed to the threat of missile attacks during the Persian Gulf War of 1991. The number of relapses during the war and the following 2 months was significantly lower than expected based on the frequency during the preceding 2 years, suggesting that not all stress conditions increase the risk of exacerbations in MS.
Fifty patients with a diagnosis of globus pharyngis and 33 control patients attending the same ENT clinic were interviewed using the (Royal Holloway &) Bedford College Life Events and Difficulties Schedule (LEDS). Information was elicited concerning life events and difficulties over the 12 months before globus onset, and this was compared with the experiences of the control patients for the year before symptom onset or, where appropriate, before the interview. Globus patients had significantly more severe events than the control patients throughout the year. Moreover, globus patients had significantly fewer close confiding relationships with their partners than did controls. There is evidence, therefore, for both psychological diathesis and social stress factors in the etiology of globus pharyngis.
The Bedford College Life-Events and Difficulties Schedule: directory of contextual threat ratings of events
- Gw Brown
- To Harris
Brown GW, Harris TO. The Bedford College Life-Events and
Difficulties Schedule: directory of contextual threat ratings of
events. London: Bedford College, University of London; 1978.