Greater mastery is associated with lower depression risk in a large international cohort of people with multiple sclerosis over 2.5 years

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease that affects the central nervous system. The multiple physical, emotional, and social challenges faced by people with MS (pwMS) have a significant impact on feelings of control over their lives. The sense of autonomy and agency, that is, the capacity to act independently and make one’s own choices, may be impaired by the impact of these challenges. When faced with stressful life events or challenges, people draw upon their inner psychological resources and characteristics. These resources can be extremely effective at assisting in developing coping mechanisms. Pearlin described psychological resources involved in coping including self-esteem, defined as the positiveness of one’s attitude towards oneself, and mastery, the extent to which one regards one’s life-chances as being under one's own control in contrast to being fatalistically ruled [1]. Self-efficacy is the expectation and confidence that the person has of their ability to employ the described psychological resource to affect an outcome [2]. Self-efficacy is part of a theoretical framework for analysing the outcomes or achievements of employing psychological resources to cope or reduce stress, of which mastery is one [2].

Studies examining self-esteem in pwMS have identified that improved self-esteem is associated with the use of strategies for improved coping and that feelings of self-worth are linked to the ability to handle challenging life situations [3]. Self-efficacy in MS has been identified as a determinant of several outcomes including perceived health status [4, 5], ability to adjust to illness [6], and health-related quality of life [7]. Mastery has also been associated with a dose-dependent improvement in both mental and physical health-related quality of life in pwMS [8].

With respect to specific health outcomes in MS, an improved sense of mastery has been demonstrated to ameliorate fatigue, the distress associated with fatigue, and the subsequent inability to perform tasks [9]. The treatment of depression in MS has been shown to improve the individual’s sense of mastery, sense of purpose in life, and their level of self-acceptance [10]. However, the impact of mastery on other clinical outcomes in PwMS has not been well-explored. This study therefore assessed the cross-sectional and prospective relationships of mastery with fatigue, level of disability, relapse number, and depression risk over 2.5 years in an international cohort of pwMS.

Of 2466 baseline participants, 1401 (58.4%) completed the survey at 2.5-year review. Of the 1401 participants, 839 (59.9%) also completed the 5-year review and are included in this analyses.

Mastery was significantly higher among those with postgraduate degrees, higher SES, more than six members in their social support network, and those who were physically active, while mastery was lower among those of progressive MS type, severe disability, with clinically significant fatigue, and with depression risk, all robust to adjustment for age, sex, education, support number, PDDS, clinically significant fatigue, depression risk, and baseline comorbidity number. Other characteristics of mastery are shown in Table 1.

We have shown that higher mastery is cross-sectionally associated with lower frequencies of depression risk, clinically significant fatigue, and severe disability, robust to adjustment, and prospectively with a lower risk of developing depression risk over 2.5 years’ follow-up. No prospective associations were seen for loss of depression risk, nor with any change in fatigue or disability, and no robust associations were seen for relapse number, either cross-sectionally or prospectively. These results suggest that developing a greater sense of mastery may prevent pwMS from developing depression, but associations with disability, relapse rate, and fatigue may reflect reverse causality.

Depression is a prevalent and debilitating symptom of MS with approximately 50% or more of pwMS experiencing a depressive disorder [20]. Our most important finding was that higher levels of mastery were associated with up to 90% reduced frequency of depression risk cross-sectionally and 60–70% lower risk of developing depression risk prospectively. These results are in accord with our earlier studies showing greater mastery was associated with significantly better mental health-related quality of life [8]. It is also consistent with other studies that demonstrated inverse associations in self-efficacy scores with depressions scores in pwMS [21, 22].

Depression in MS occurs more frequently than in the general population, potentially resulting from the same inflammatory aetiologic factors, and/or a consequence of the effects of MS and its clinical progression[23]. Regardless of its genesis, there is a potent role for stress in realising depression in pwMS, since peripheral inflammation can disrupt normal mood via the hypothalamic–pituitary–adrenal (HPA) axis, and likewise potentially the realisation of general inflammation due to stress through the same pathway [23]. This interaction provides a route by which stress reduction might lead to reduced depression risk. Our results are consistent with studies in both established MS [22, 24] and recently diagnosed MS [25], showing that persons of higher resilience have less depression and better quality of life. It is possible that persons of greater mastery are more resilient and thus, less at risk of becoming depressed due to the effects of their disease. It is also possible that persons who are more resilient may represent a particular population for whom the inflammatory effects of disease do not realise as much mood disruption via the HPA axis. Both these interpretations would align with the prospective finding that pwMS of higher mastery were less likely to develop depression risk. If, the resilience mechanism is valid, this represents a point of intervention for pwMS to reduce their risk of depression. Through mindfulness or other mental health interventions, resilience and mastery could be increased and could contribute to a reduced risk of developing depression.

Another possibility is that greater mastery could lead to an increased likelihood to engage in positive lifestyle behaviours like physical activity, cognitive training, or other social behaviours that could potentially realise the positive impacts on depression risk. Examination of these relationships would also be worthwhile.

Our findings for other clinical outcomes assessed are less indicative of a true association, being only present cross-sectionally for fatigue and disability but not prospectively. Previous studies have reported similar findings of an association between fatigue and mastery and related concepts in pwMS. For example, in a cross-sectional study of 139 pwMS, higher environmental mastery, the ability to create an environment suitable to one’s needs, assessed by a subdomain of the Ryff Happiness Scale [26], was inversely associated with fatigue severity [9]. For disability and mastery, less has been done. The aforementioned study by Schwartz and colleagues found no relationship between the Ryff Happiness Scale and disability as measured by EDSS [9]. Other prospective cohort studies of this relationship are yet needed to make definitive conclusions.

It is possible that increased resilience and less stress-associated inflammation could have a similar effect on relapse as seen for depression on risk of relapse. This is suggested by our data as those in the top quartile of mastery had a lower risk of increasing relapse number during follow-up; however, this was not significant after adjustment. That no associations were seen between mastery and relapse may be attributed to deficiencies in the measure. Participants were asked to report the number of doctor-diagnosed relapses they had experienced in the previous year. Such measures are unfortunately quite susceptible to recall bias and recall error, and a prospective measure of relapses would have been preferable. Thus, we are cautious in the interpretation of these results. There has been no investigations of mastery and relapse risk in MS so we have no ability to compare with the literature on this topic. Other studies of the mastery-relapse relationship should be undertaken, ideally prospective in nature so as to better assess causality of associations, if any.

Our study has many strengths, comprising a large international cohort of pwMS, utilising a prospective study design, and including a diversity of demographic, clinical, lifestyle, and outcome measures. The sample size gives us significant statistical power. We acknowledge appreciable attrition from our baseline survey, with 34.0% retention. This is to some extent a function of the healthy participant bias attendant to many longitudinal epidemiological studies, but may reflect the online nature of recruitment that can impact on loss of contact due to changed email addresses as well as a lack of a more personal contact that come from clinic-based studies. Given our exposure, mastery, and our outcomes of clinical severity, particularly depression, there is potential for attrition to impact on our observed results. That said, while we have lost some proportion of people with higher levels of depression, fatigue, and relapse rate, and lower mastery, that we continue to show a robust prospective relationship with mastery and subsequent depression risk may indicate the findings here underestimate a true effect. Assessments of these relationships in other samples, particularly with less attrition and attendant healthy participant bias, are worthwhile.

Other limitations include the self-reported nature of the survey, including MS diagnosis and MS phenotype, as well as clinical outcome measures. However, measures such as mastery and fatigue are necessarily subjective in nature, and validated tools were used wherever possible. Our prospective study design gives us the ability to assess causal directionality. The comprehensive data capture allows us to develop robust multivariable models that control for a great deal of potential confounding. Another potential limitation lies in not accounting for cognitive impairment as this might modulate the mastery-outcome relationships.

Our measure of depression only queried depression symptoms in the preceding two weeks, whereas it is possible that people may have developed and resolved depression symptoms in the 2.5-year period between reviews but before the two weeks before they completed the PHQ-9. Thus, a study seeking to validate these results might endeavour to seek additional modes of assessing depression, either more frequent survey or linkage with clinical data whereby greater ascertainment of depression symptoms could be made.

Finally, while mastery is a mode of assessing personal capacity to cope with stress and other issues, a related measure which we do not have measurement of is self-efficacy. Self-efficacy has been described as altering one’s expectations of mastery and success in a positive fashion to mental wellbeing [27]. While a related measure, mastery is distinct in being a function of the ability of the person to feel themselves in control of their lives [1], whereas self-efficacy includes elements of this, as well as social desirability, interpersonal competency, ego, and self-esteem [27]. While we believe that sense of self-control is important in coping for people with MS and thence to potentially have effects on aspects of mood and clinical progression, certainly for depression as an outcome, the other elements included in self-efficacy could be important as well. Moreover, mastery and self-efficacy would likely relate and so greater mastery could improve self-efficacy, as has been demonstrated in other settings [28]. Thus, a study seeking to replicate these results might include self-efficacy alongside measures of mastery.

We have shown a strong positive association of higher mastery with less risk of depression, and a lower risk of developing depression in the future. Building mastery and resilience may thus represent a point of intervention to improve mental health in pwMS.