Behavioral Activation Therapy for Multiple Sclerosis: Potential Effects on Cognition, Neuropsychiatric Symptoms, and Quality of Life

Abstract

Behavioral activation therapy (BAT) was initially developed to treat depression and was subsequently extended as a transdiagnostic therapy for other psychiatric and neurocognitive disorders. However, research on its impact in people with multiple sclerosis (MS) is lacking. We suggest that MS-adapted BAT reduces neuropsychiatric symptoms, neurocognitive impairment, social isolation, and impairment of activities of daily living—key components of MS-related quality of life. Our proposed adaptation of the traditional therapy includes a focus on increasing engagement in cognitive, physical, or social activities (activity demand characteristics) to improve cognition and daily life function. In addition, these activities should be individually perceived as energizing, relaxing, or meaningful (subjective activity characteristics) to benefit neuropsychiatric symptoms and social connectedness. Finally, we propose that BAT in MS should specifically focus on reducing stressful activities (i.e., unenjoyable, high-arousal activities) and increasing relaxing activities (i.e., enjoyable, low-arousal activities), as this dimension might tackle the neuroinflammatory etiology of MS.

1. Introduction

Behavioral activation therapy (BAT) is a practical and effective therapeutic approach grounded in the pioneering work of Peter Lewinsohn, who introduced the concept as part of his behavioral model of depression in the 1970s [1]. It was developed specifically to address depression by increasing engagement in enjoyable activities, counteracting the depressive pattern of withdrawal and inactivity (see Figure 1a). Since its inception, the therapy has been extended to include not only enjoyable activities but also meaningful ones, aligning these activities with the individual values of patients (see Figure 1b). Initially integrated within traditional cognitive–behavioral therapy, BAT evolved into an independent treatment [2]. Its development as a standalone therapy was advanced by Jacobson et al. in the 1990s, who demonstrated that BAT alone could effectively improve mood without the need for extensive cognitive restructuring [2]. Indeed, the effects of BAT on depressive symptoms are comparable to or even greater than the effects of cognitive-behavioral therapy [3,4]. Importantly, the beneficial effects of BAT are not limited to depressive symptoms [5,6]. BAT has shown improvements in other neuropsychiatric symptoms, including internalizing symptoms such as anxiety [7] and externalizing symptoms such as substance use [8]. Additionally, it has increased feelings of social connectedness [5,6,9].

Recently, BAT was extended again to target neurocognitive disorders (NCDs) including the impairment in cognition, daily functioning, and quality of life [10,11,12,13]. Enjoyment and meaningfulness of activities—the two effective subjective activity characteristics—have been complemented by three activity demand characteristics that protect against cognitive decline and functional impairment [10,11], namely the cognitive, physical, and social demands of activities (see Figure 1c). This adapted BAT—targeting cognitive, physical, or social activities that are individually perceived as enjoyable or meaningful—reduced memory decline and improved executive function and daily life functioning after 2 years in adults with mild cognitive impairment [10]. In addition, NCD-adapted BAT improved quality of life in adults with mild cognitive impairment and mild dementia [11,12,13] (see Figure 1c,e).

Importantly, BAT is scalable, as it can be effectively conducted by junior mental health workers [3], tele-delivered by lay counselors [9], or via fully automated digital apps [11]. In addition to its relatively low costs, BAT has the potential to provide economic benefits by reducing drug costs, decreasing hospital admissions, and minimizing absenteeism from work for family members, thereby easing the financial burden on both patients and their environment.

Taken together, BAT is a scalable, cost-effective, transdiagnostic therapy that demonstrates beneficial effects on neurocognition, neuropsychiatric symptoms, daily functioning, and social connectedness—key areas of MS-related impairment that affect patients’ quality of life.

To our knowledge, the effect of BAT in MS has not been investigated so far. However, initial evidence from Turner et al. (2019) indicates that principles of BAT, such as increases in goal-directed activation, mediate the beneficial effects of physical activity counseling on depressive symptoms in MS [14]. This study showed that physical activity counseling, compared to physical activity education improved goal-directed activation at 3 months, which in turn was related to improved depression at 6 months [14]. Goal-directed activation was measured with the Activation subscale of the Behavioral Activation for Depression Scale (BADS), which is based on seven items representing the completion of activities that are goal-directed, focused, scheduled, diverse, and worth performing [14]. This means that the mechanisms by which physical activity counseling improves depression are based on subjective characteristics of completed activities that are not directly related to the physical demands of the activities [14]. This finding demonstrates that in addition to the physical demands of activities, subjective activity characteristics related to BAT (e.g., increases in goal-directed activation) are decisive for beneficial counseling effects.

2. Proposed MS-Adapted Behavioral Activation Therapy

In the following, we discuss potential limitations of BAT in patients with MS while proposing how BAT should be adapted to better meet their requirements. A first potential limitation addresses the high prevalence of fatigue in MS. Physical and cognitive fatigue in MS can make activities of daily living overwhelming, leading to withdrawal from leisure activities. Therefore, rather than mainly focusing on activation, MS-adapted BAT should focus similarly on both (i) a reduction in activities that are incongruent with BAT principles (e.g., reducing unenjoyable activities) and (ii) an increase in activities aligned with these principles (e.g., increases in enjoyable activities) (see red arrows at the left and green arrows at the right in Figure 2).

Enjoyable activities can be categorized into activities that induce a high and a low arousal level (see top and bottom in Figure 2).

Playing exciting games, visiting sports events, or dancing are examples of activities that are often perceived as high-arousal enjoyable activities, i.e., energizing activities (see green diagonal axis from bottom left to top right in Figure 2). In contrast, taking a warm bath, practicing yoga, or reading a book are typically experienced as low-arousal enjoyable activities, i.e., relaxing activities (see blue diagonal axis from top right to bottom left in Figure 2). To account for the high prevalence of fatigue, the neuroinflammatory underpinning of MS, and the fatiguing and pro-inflammatory effects of stress, we suggest that it is especially important for this population to increase the engagement of relaxing activities and to decrease stressful activities (see green and red arrows in the top left and bottom right in Figure 2).

The negative impact of chronic stress on inflammation, MS onset, MS relapses, cognition, and neuropsychiatric symptoms has been shown and investigated for decades [16,17]. Emerging research highlights that psychological interventions may exert effects on the MS etiology by modulating immune function [18]. In autoimmune diseases like MS, a chronic condition characterized by neuroinflammation and demyelination, immune dysregulation is a hallmark feature. Chronic stress, common in MS, is known to exacerbate neuroinflammation through sustained activation of the hypothalamic–pituitary–adrenal (HPA) axis [16,17]. This leads to a prolonged secretion of glucocorticoids such as cortisol, which initially suppresses inflammation but can paradoxically promote pro-inflammatory states when dysregulated [16,17].

By reducing stressful activities and fostering engagement in relaxing activities, BAT could potentially counteract these harmful stress-related immune effects. Relaxing activities may lower the activity of the HPA axis and sympathetic nervous system, thereby reducing the release of stress hormones like cortisol and catecholamines [16,17]. Evidence suggests that mindfulness-based interventions and yoga—activities often categorized as relaxing—can modulate stress hormone levels and shift the immune profile from a pro-inflammatory (Th1/Th17-mediated) to an anti-inflammatory (Th2/Treg-mediated) response in MS [16,17].

In addition, rather novel findings indicate that stress has a negative impact on mitochondria [19], mitochondrial alterations are observed in MS [20], and mitochondrial activity is linked with neurocognition and psychiatric symptoms [21]. Taken together, BAT-induced increases in relaxing activities and decreases in stressful activities may improve neurocognitive and psychiatric symptoms mediated by its impact on immune function, neuroinflammation, and mitochondrial function (see 3a in Figure 3).

It is long known that stress increases neuropsychiatric symptoms [22]. Recent findings indicate that engaging in relaxing activities is associated with reduced neuropsychiatric symptoms [22]. In addition, activities that are often perceived as relaxing such as mindfulness-based interventions and yoga have improved quality of life and fatigue in patients with MS, respectively [23,24] (see 3a in Figure 3).

Finally, due to the high prevalence of fatigue, it may be especially important for patients with MS to break down activities into manageable steps, gradually increasing activity levels in a way that accommodates their level of fatigue. Even though most patients with MS are able to engage in cognitively, physically, and socially challenging activities without experiencing post-exertional malaise [25], fatigue-related adverse events due to BAT should nevertheless be tracked carefully.

A second limitation for the feasibility of BAT in MS may result from MS-related cognitive impairment, such as memory deficits, attention difficulties, and slowed processing, which may impair a patient’s ability to adhere to the structured steps of BAT and to select activity goals that are cognitively demanding but not overwhelming [26]. In cases where BAT is performed by therapists, they should carefully consider cognitive impairments by adjusting the complexity and cognitive demands of the therapeutic procedure and of potential activity goals accordingly (e.g., less choices in potential activity goals and more support in generating ideas for activities). A greater challenge may be the feasibility of fully automated digital BAT apps because of potential usability issues in patients with cognitive impairments. However, good feasibility of a fully automated digital BAT app in people with MCI and mild dementia was recently demonstrated [11]. The app uses a highly structured procedure, sufficient repetitions of educational content, a very simple design, and recommendations on how to adapt activities according to patients’ abilities [11].

The third limitation is related to physical motor impairments in MS. These include weaknesses, spasticity, as well as balance and coordination issues, which can make it difficult for patients to perform physical activities. In line with Kalb et al. (2020), BAT should be adapted according to patients’ Expanded Disability Status Scale (EDSS) values [27]. For all patients, injuries and falls need to be tracked carefully while determining their relationship with activities performed in the context of BAT. Patients with an EDSS ≥ 5 may be supported by a specialist (i.e., physical or occupational therapist, exercise or sport scientist, experienced in MS). For patients with an EDSS ≥ 7, specialists must guide adaptations of physical activities, or these activities should be excluded from BAT. Adaptations of physical activities include all kinds of adaptive sports (using equipment such as recumbent hand-cycle, three-wheel bikes), water exercises, seated exercises, and explanations of cooling strategies for heat-sensitive patients [27].

For example, yoga can be modified according to physical motor impairment, especially balance problems, by focusing on gentle restorative practices such as chair yoga, breathing techniques, and mindfulness. These adaptations can make yoga accessible for MS patients with a wide range of physical motor impairment.

Finally, BAT-related recommendations for specific activities with regard to activity demand characteristics should be based on evidence: For example, playing chess and solving jigsaw puzzles have been studied with regard to cognitive demands and benefits [28,29,30]. These activities engage cognitive functions, such as memory, attention, and problem-solving skills—abilities that are affected in individuals with MS [28,29,30]. The cognitive benefits induced by cognitively demanding activities seem to be mediated by neuroplastic processes that enhance neural efficiency [31]. According to the guided plasticity facilitation framework, integrating physical and cognitive activities in temporal proximity could induce synergistic effects. Physical activity demands could increase the plastic potential (e.g., through the release of the brain-derived neurotrophic factor and other neurotrophic factors), while cognitive activity demands may guide this facilitated neuroplasticity by inducing specific changes in neuroconnectivity that increase neuronal efficiency (e.g., through the long-term potentiation of neurons that fire together; see number 3a in Figure 3).

3. Conclusions

We suggest how the potential limitations of BAT in MS due to fatigue, cognitive, and physical motor impairment can be overcome. MS-adapted BAT should integrate increases in relaxing, energizing, or meaningful activities (subjective activity characteristics), with increases in cognitive, physical, or social activities (activity demand characteristics). Activity reductions in detrimental activities and increases in beneficial activities should be focused to a similar degree. In contrast to traditional BAT, we propose that a special focus on reducing stressful activities and increasing relaxing activities might benefit patients with MS even more, as it may tackle its biological etiology (e.g., inflammatory, immune, and mitochondrial processes). We propose that MS-adapted BAT modulates the immune and mitochondrial profile, reduces neuroinflammation, supports remyelination processes, and key components of health-related quality of life in MS including neuropsychiatric symptoms, neurocognitive impairment, social isolation, and impairment of activities of daily living(see Figure 1e and Figure 3). We assume that this holistic approach not only addresses the psychological dimensions of MS but also targets the biological underpinnings of the disease, offering a promising avenue for future research and clinical application.

Overall, MS-adapted BAT offers a promising approach for improving quality of life for patients with MS. Now, researchers need to put it to the test in randomized controlled trials. Further research should focus on optimizing its application for patients with varying functional limitations and exploring the biological mechanisms underlying its positive effects.