In the present study, the concurrent validity of DASS-21 was assessed through the desirable and acceptable correlations of its subscales with other constructs that are expected to have significant positive or negative relationships with these subscales. The findings showed that all the three subscales of DASS-21 in MS patients have a significant positive relationship with fatigue and a significant negative relationship with the eight dimensions of health (in SF-36). Consistent with this finding, previous studies have reported that MS patients with higher scores on symptoms of depression, anxiety, and stress experience higher intensities of fatigue and lower levels of health components (
4,
5,
17). A possible explanation is that depression, anxiety, and stress can have a negative impact on self-efficacy, self-worthiness perception, and the coping resources of the patients, which can lead to a reduction in health-related quality of life. The etiology of fatigue is not clear and is a multifactorial phenomenon as well. Thus, it is likely that effective biological changes in depression, anxiety, and stress can lead to exacerbation of fatigue.
The assessment of the predictive validity of DASS-21 showed that scores of depression, anxiety, and stress can explain a significant ratio of the variance of fatigue. In this regard, Greeke et al. (
40) found that depression and fatigue have a significant relationship, and the change over time in depression leads to fatigue exacerbation. In a study on 122 MS patients, Labuz-Roszak et al. (
6) identified depression and anxiety as significant predictor variables for fatigue. Recently, Brenner et al. (
41) reported a significant correlation between depression and fatigue, while there was no relationship between stressful life events and fatigue. Additionally, another study using path analysis showed that depression has a direct effect on fatigue in MS patients and can predict it (
42). A basic explanation for these results is the role of biological processes (
41). It seems that psychological symptoms may be related to fatigue in terms of etiology and through inflammatory processes (i.e., cytokines, leading to the appearance of sickness behavior). Cytokines are central to the pathogenesis of MS (
43). For example, Martins et al. (
44) indicated that MS patients have elevated serum levels of both pro- and anti-inflammatory cytokines. In the meantime, one of the cytokines reported in MS is interleukin-6 (IL-6) (
41). Levels of IL-6 increase sensitivity to stress (
45) and are associated with fatigue (
41). Theoretically, it can mediate stress activation and fatigue exacerbation. There is also a possible connection between stressful life events and MS exacerbations (
46) that can lead to exacerbation of fatigue.
Moreover, despite the distinction between depression and fatigue, there is a great deal of overlap between their symptoms. For example, depression can predict later fatigue, and fatigue can predict later depression (
7). Therefore, more detailed and comprehensive studies are needed to examine the underlying biological mechanisms of psychological symptoms and fatigue. Some conflicting results may be due to the use of different methods and questionnaires to diagnose both fatigue and psychological symptoms as well as reporting bias.
Our analyses also showed that DASS-21 after controlling the confounding factors has been able to predict all aspects of SF-36. Although similar studies that examine each aspect of health-related quality of life separately are limited, this finding is consistent with some previous results. In a recent study, Fernandez-Munoz and colleagues (
42) demonstrated that depression with two components of SF-36, including bodily pain and mental health, were significantly associated with MS patients, while there was no relationship between depression and physical function. Kargarfard et al. (
25) found that depression in MS patients could predict health components, including role limitations due to emotional problems, pain, emotional wellbeing, health perception, cognitive function, and health distress. Although depression could not predict the components of physical health, role limitations due to physical health, energy, social function, and sexual function. However, in their study, the multiple sclerosis quality of life questionnaire was used to measure health, which has more and different subscales from SF-36. Nourbakhsh et al. (
24), in a longitudinal study, revealed that changes in depression were associated with changes in the components of physical health in SF-36. Barzegar et al. (
23) in a comparative study on two groups of MS patients and neuromyelitis optica spectrum disorder, reported that depression and anxiety were independent and significant predictors of mental health dimensions. In addition, Enns et al. (
47) showed that depression and anxiety can predict general functional impairment in a group of patients with inflammatory bowel disease, MS and rheumatoid arthritis even after accounting for the effects of demographic, clinical and psychological variables. It seems that depression, anxiety, and stress can decrease mental and physical health by energy depletion, decline in activity, reduction of participation in social practices, impairment in daily functioning, and weakness in positive thinking in MS patients. This indicates that the development and expansion of therapeutic interventions for MS patients aimed at reducing the symptoms of depression, anxiety, and stress can lead to the reduction/prevention of clinical fatigue symptoms and improved health components in these patients. This hypothesis is supported by a review reporting that appropriate intervention produced improvements in both physiological and physiological aspects in MS (
48). In this case, the psychological treatments with the highest recommendation grade are cognitive behavioral therapy (CBT) and interpersonal therapy (IPT) (
49). It is worth mentioning that CBT can be administered individually, in a group setting, or by the computer; all of which have shown efficacy in MS patients with low dropout rates (
50,
51).