1 A comprehensive review of behavioral activation treatment for depression 2 Xiaoxia Wang1, Zhengzhi Feng2,* 3 1 Department of Basic Psychology, College of Psychology, Army Medical University, 4 Chongqing, China 5 2 College of Psychology, Army Medical University, Chongqing, China

6 Abstract Behavioral activation (BA) treatment has evolved from a component of 7cognitive behavioral therapy (CBT) and has become standalone psychotherapy for depression. 8The rapid increasing application of tele-mental health approaches such as telephone-, internet-, 9and smartphone-based interventions with BA were emphasized. With its efficacy comparable to 10traditional CBT, and its evidenced-based cost-effectiveness, BA is promising to be developed 11into a guided self-help intervention. The efficacy across diagnoses and effective components of 12BA treatment were reviewed. With the rise of the third wave of psychotherapy, therapeutic 13components across diagnoses will be incorporated into behavioral activation therapy. However, 14extensive studies are required to examine the neural and modulatory mechanism of BA for 15depression, and to explore the feasibility and necessity of tele-mental health BA application into 16the healthcare system. 17 Keywords behavioral activation treatment; depression; tele-mental health; cost- 18effectiveness; guided self-help intervention 19

20 During its developmental process, cognitive behavioral therapy (CBT) for depression has 21gradually incorporated and integrated problem-solving therapy, self-control therapy, traditional 22cognitive therapy, and other therapeutic components [1]. The unique role of behavioral activation 23(BA) therapy has gradually been recognized, with the increasing accumulation of evidence-based 24BA for depression that systematically reinforces patients' behaviors related to environmental 25reinforcement and improves negative thinking, emotions, and overall quality of life [2]. The 26National Institute of Mental Health (NIMH) (2005) claims “behavioral activation as a more 27simply behavioral form of CBT”. Contemporary behavioral activation therapies also include 28many variations, which add certain therapeutic components to address factors that sustain or 29exacerbate depressive symptoms [3]. 30 As a behavioral therapy strategy for depression, behavioral activation is derived from 31Lewinsohn’s pleasant events scheduling [4]. Rehm proposed a self-control model of depression 32and defined self-control as the process of an individual changing their response frequency in the 33absence of immediate external support [5]. He also proposed a self-control therapy program that 34promotes cognitive and behavioral changes through self-monitoring, self-evaluation, and self- 35reinforcement [5]. 36 Beck integrated the behavioral activation strategy into the framework of cognitive 37therapy and stated that behavioral activation should be the first treatment step for depression, 38especially for severe depression. Therefore, the goal of behavioral activation should precede

11 Correspondence: Dr. Zhengzhi Feng, [email protected]. 2 1 3 39cognitive monitoring and modification. One of the contributions of Beck's cognitive therapy to 40behavioral strategies is standardizing behavioral monitoring and programs. This facilitated the 41integration of cognitive orientation and behavioral orientation and gave birth to cognitive 42behavioral therapy (CBT). 43 Behavioral activation therapy can be regarded as the return of behavioral orientation after 44CBT. David Barlow proposed that the common strategy of many psychotherapy methods is to 45adjust behavioral orientation at the time of emotional disorders—when used to treat specific 46disorders, emotional and behavioral activation is a powerful tool, especially for specific contexts. 47Hollon and Garber define behavioral activation as a series of treatment programs during 48cognitive therapy [6]. Jacobson and his colleagues used this term to describe behavioral 49interventions through cognitive therapy [7]. They analyzed the components of CBT and found for 50the first time that the treatment effect of behavioral activation was equivalent to that of CBT, 51including the three components of behavioral activation, cognitive reconstruction of automatic 52thinking, and cognitive reconstruction of core beliefs [2]. In the subsequent literature, behavioral 53activation therapy was described as a standalone therapy for depression [7]. 54 1 Psychopathological models of behavioral activation therapy 55 Studies on the causes of behavior mainly use two animal models: response-based and 56action-based model [8]. The response-based model offers a mechanistic explanation for the 57causes of behavior. It assumes that behavior occurs in response to elicited, released, or triggered 58stimuli; therefore, behavior is regarded as a type of response, including physiological reflexes, 59ecological fixed behavior patterns, and conditional and unconditional psychological responses. 60The action-based model offers a teleological explanation that behaviors are not triggered by 61stimuli but are controlled by animals' perceptions of the consequences of actions. Such behaviors 62are regarded as intentional and purpose-oriented and thus are actions. For goal-oriented systems 63(organisms), changes in motivation or a new understanding of goals and values can lead to 64changes in goals and values [8]. Both models are reflected in behavior-oriented psychopathology 65models of depression. 66 1.1 Response-based reinforcement model 67 According to the psychopathological model of depression, the loss, reduction, or long- 68term low level of positive reinforcement leads to behavioral and emotional changes in depressed 69individuals. Houston, for example, argues that the absence of reinforcement (such as foraging 70animals) or the withdrawal of reinforcement (such as expecting to be rewarded again) leads to 71the extinction of behaviors, with frustrated, emotional, and arousal behaviors such as irritability 72and attacks. Generalization of such extinction to other contexts will produce behaviors similar to 73absence of anhedonia; this behavior model is known as extinction-induced depression (EID) [9]. 74Regarding the nature of reinforcement, researchers have assumed either positive reinforcement 75or negative reinforcement. For example, Lewinsohn believes that the withdrawal/reduction in 76response-contingent positive reinforcement (RCPR) can fully explain the occurrence of 77depression [10]. Behavioral activation mediates the increase in RCPR and decrease in depressive 78symptoms [11]. Other researchers have focused on the role of negative reinforcement on 79avoidance and withdrawal. For example, Ferster argues that the withdrawal of discriminative 80stimuli can lead to avoidance and withdrawal and that depression is caused by negative 81reinforcement of avoidance and escape behavior [12, 13]. Martell also suggests that negative

4 2 5 82emotions associated with low-level positive reinforcement and aversive stimuli in the 83environment can lead to persistent and excessive avoidance/escape behavior [14]. 84 The goal of behavioral activation therapy is to enhance behavioral activation (activity), 85which then leads to more positive reinforcement to improve depressive symptoms [15]. 86Therefore, individualized behavioral activation therapy includes (1) discerning the living 87environment that induces depression—for example, a decrease in positive reinforcement of 88healthy behaviors and an increase in positive reinforcement (or negative reinforcement) of 89depressive behaviors lead to increased depression—and (2) clarifying the coping pattern that 90sustains and exacerbates depression. When depressed individuals identify environmental stimuli 91as aversive and threatening, they will adopt avoidance behaviors, i.e., trigger-response-avoidance 92pattern (TRAP), thus exhibiting less behavioral activation and more avoidance and depressive 93behaviors. Non-adaptive coping patterns will further lead to a decrease in positive reinforcement 94of healthy behaviors and an increase in positive reinforcement (or negative reinforcement) of 95depressive behaviors in the environment, leading to more depressive symptoms. Accordingly, the 96aim of behavioral activation therapy is to teach patients behavioral activation techniques, in order 97to enhance behavioral activation and reduce avoidance and depressive behaviors, thereby 98promoting the trigger-response-alternative cope (TRAC) pattern, which breaks the TRAP 99between the depressive living environment and the non-adaptive coping pattern and helps 100individuals adopt an adaptive pattern to cope with adverse stimuli. 101 1.2 Action-based models 102 With the development of cognitive neuroscience, current behavioral activation therapy is 103paying more attention to the role of cognitive components such as goals and values in activating 104behaviors. 105 According to the psychopathological models of behavioral activation therapy, two 106components may have a therapeutic effect. The first is the actual rewards received, and the 107second is the expectation of possible rewards. According to the depression decision model, the 108vigor and frequency of individual instrumental behaviors are determined in part by expectations 109of average rewards. If the expectation is low, individuals will demonstrate sloth, i.e., lower 110tendency for individual action, diminishing the individual’s ability to receive rewards and 111sustaining his/her incorrect estimate of the average environmental rewards. Therefore, a low 112expectation of rewards can explain how depressive behaviors are sustained [16]. In terms of 113behavior, studies have shown that for depressed individuals, expected happiness is the most 114significant factor in predicting the decrease in depressive symptoms after behavioral activation 115therapy, with greater predictive power than the actual rewards received [17]. The difference 116between expected rewards and actual rewards received, i.e., prediction error, has no significant 117predictive effect on depressive symptoms. Further research shows that mental imagery of future 118positive events and their results can improve the level of behavioral activation. One possible 119reason is that the use of positive imagery makes individuals more likely to actually participate in 120imagining these activities; another possible reason is that through mental imagery, individuals 121can anticipate and experience the happiness that positive events can bring [18]. 122 In terms of neurological mechanisms, studies have shown that for depressed individuals, 123behavior therapy increases the activation intensity of the caudate during the stage of expected 124rewards, the activation intensity of the putamen during the stage of action selection, and the 125activation intensity of the medial orbitofrontal cortex (mOFC) and the dorsolateral prefrontal

6 3 7 126cortex (DLPFC) during the stage of reward feedback [19, 20]. In addition, for individuals with 127subthreshold depression, receiving behavioral activation increases the activation intensity of the 128left ventrolateral prefrontal cortex (VLPFC) during the stage of expected loss [21]. These studies 129show that depressed individuals demonstrate neurological dysfunction in reward expectations, 130which may lead to a decrease in reward-seeking behaviors and a subsequent loss of anhedonia. 131 2 Clinical practices of behavioral activation therapy 132 2.1 Sessions 133 Current psychotherapies for depression include CBT, marriage/couple/family counseling 134and therapy, mental education, fitness, problem-solving therapy, self-help therapy, and 135behavioral activation therapy [22]. Compared with current mainstream psychopathological 136models of depression, such as Beck's cognitive model, and other theoretical models that 137emphasize biological or sociological causes, behavioral activation therapy focuses more on the 138context of depression [23], namely, the interaction between individuals and environment. 139Therefore, the treatment goal focuses on the sense of control of and pleasure with the activity 140and the functionality of the activity, such as good social adaptation and interpersonal 141relationships [24]. As a structured approach to short-term psychotherapy, behavioral activation is 142designed to (1) encourage patients to become more involved in adaptive activities that bring 143pleasure or the sense of control, (2) reduce patient participation in activities that sustain 144depression or increase the risk of depression, and (3) solve the issue of not receiving rewards or 145aversion management. There are three primary treatment goals: (1) discern the context that 146induces depression, (2) identify the coping patterns that sustain and exacerbate depression, and 147(3) develop a treatment plan to improve the coping patterns and increase exposure to 148environments with positive reinforcement. The therapy increases adaptive activities (usually 149related to pleasure or the sense of control), reduces activities that sustain depression or increase 150the risk of depression, helps patients eliminate obstacles in the process of receiving rewards, and 151reduces self-control behaviors as an effort to avoid punishment [3]. 152 The Jacobson’s treatment includes 20 sessions that involve (1) monitoring daily 153activities; (2) assessing the pleasure and sense of control associated with various activities; (3) 154assigning increasingly difficult tasks that may reduce pleasure or the sense of control; (4) 155conducting cognitive rehearsals, during which patients imagine themselves participating in 156various activities to identify factors that may prevent patients from gaining pleasure or the sense 157of control from the activities; (5) discussing specific issues such as difficulty sleeping and 158behavioral therapy techniques to deal with these issues; and (6) taking measures to improve 159social skills such as confidence and communication skills. On the basis of Jacobson’s regimen, 160Martell, Addis, and Jacobson (2001) developed a more comprehensive manual for behavioral 161activation therapy and expanded the areas covered from initial behavioral avoidance to other 162intervention strategies for behavioral activation, such as repeated freedom from issues or 163unpleasant events, mindfulness training, and self-reinforcement [25]. The primary treatment 164goals include (1) discerning the living environment that induces depression, (2) clarifying the 165coping patterns that sustain and exacerbate depression, such as chronic negative cognitive bias 166and social withdrawal, and (3) constructing a treatment plan to improve coping patterns to 167increase exposure to positive reinforcement in the living environment. It also includes a series of 168behavioral activation strategies such as activity schedules, tasks with hierarchical difficulties, 169tackling avoidance behaviors.

8 4 9 170 Alternatively, Lejuez, Hopko, and Hopko (2001) developed a brief, 12-session regimen 171that includes only components directly related to behavioral activation. They named the regimen 172brief behavioral activation treatment for depression (BATD), which includes daily monitoring, 173social support contracting, activity selection and scheduling, and post-activity rewards. They also 174published a treatment manual in the same year [26] with proven efficacy for depression in 175hospital patients [27], cancer patients [28], and patients with both depression and anxiety [29]. 176 A decade later, Lejuez published the revised BATD treatment manual (BATD-R) [30], 177which shortens the number of sessions from 12 to 10. Detailed revisions include (1) more 178emphasis on the basic principles of treatment, including client-therapist relations; (2) clearer 179descriptions of life, values, and activities; (3) simplified and fewer treatment modalities; (4) 180more details about the program, including a concept review of obstacle elimination and late-stage 181treatment; and (5) a new revised daily monitoring schedule for patients with low education levels 182[30]. Lejuez et al. state that the number of sessions may be adjusted according to the patient and 183clinical context. For example, more sessions may be required for patients who resist treatment or 184patients with more complex clinical conditions. Conversely, five sessions may be sufficient for 185clearly defined cases (sessions 6 to 10 are mainly review and additional practice about key 186elements), and adding additional practice may prolong the treatment process. For different 187versions of behavioral activation therapy, some researchers believe that behavioral therapy can 188be used in depressed patients with more complex symptoms and that BATD is more suitable for 189depressed patients indicated for brief and well-defined treatment [31]. The procedures of 190Lejuez’s model are more stringent than those of Jacobson’s model. They include (1) providing 191mental education about depression and treatment principles; (2) establishing a baseline level of 192activity and creating a healthy treatment environment; (3) identifying potential activation 193activities on the basis of value assessment; and (4) setting activity goals and monitoring activity 194progress. In addition, treatment compliance is enhanced with rewards or reinforcement [32]. 195 Despite variations in detailed operations, all behavioral activation therapies share the 196following components: (1) daily activity schedule, which lists daily activities that are 197functionally related to depressive symptoms, are either designed or selected from the patient's 198daily activities, and can stimulate a sense of control and pleasure, block avoidance behavior 199patterns, correct daily behavior habits, and/or help individuals to better act in line with personal 200values, and (2) an emphasis on action based on scheduled and unscheduled daily activities, rather 201than personal emotions or immediate wishes. Behavioral activation therapy assumes that an 202individual must change his/her actions in order to change his/her emotions, which emphasizes 203changes from the outside in [14]. In contrast, earlier behavioral activation therapy encouraged 204patients to participate in seemingly pleasing activities, such as walking or have a meal with 205friends. Later, the concept of behavioral activation therapy was redefined. The focus is no longer 206about scheduling as many activities as possible with positive reinforcement but, rather, activities 207with positive reinforcement that block avoidance behavior patterns to make it easier for patients 208to achieve their personal life goals. More recent therapies have added some treatment 209components to target factors that sustain or exacerbate symptoms, such as social skills training, 210relaxation training, time management, contracting, problem solving, goal setting, distraction 211from thoughts that create stress, and hierarchy task setting [3].The British National Institute for 212Health and Care Excellence (NICE) guidelines recommend that each session of behavioral 213therapy and CBT should be 60-minute face-to-face therapy for 12 months.

10 5 11 214 Computerized intervention includes 10 sessions. Sessions 1 to 5 focuses on mental 215education about depression and behavioral activation therapy, clarify values and their relation to 216behaviors, perform functional assessments, arrange homework and set activity schedules, and 217monitor daily behaviors and their relation to emotions. Professional actors act as patients and 218show depressive symptoms and how to implement behavioral activation therapy. At the 219beginning and end of treatment, a female narrator introduces the treatment goals and provides a 220treatment overview. During each session, depressive symptoms are measured to quantify the 221change in symptoms. Session 5 evaluates whether the patient has sufficient knowledge to 222proceed to sessions 6 to 10. If so, sessions 6 to 10 focus on achieving the core content of 223behavioral activation therapy. If not, the program will automatically jump back to an earlier 224session based on the evaluation score of session 5. Sessions 6 to 10 include interactive 225microcourses to guide patients to acquire specific skills, such as activities that enhance 226adaptation or constructive activities, anger control, effective communication, relaxation 227techniques, setting and achieving goals, breaking down tasks, improving sleep quality, and filling 228out job applications. These microcourses are developed based on the comprehensive evaluation 229during session 5. High-priority content is played first, followed by low-priority content. To 230assess the suitability of the microcourse assignments, the patients are asked to answer several 231questions about the difficulty of the course content and are quizzed to test their understanding 232about the principles of behavioral activation therapy. Most high-priority content is played by 233session 8. During each session, the patient is required to actively interact with the computerized 234program, which assesses patient understanding of the content, assignment completion, and any 235confusion about the treatment based on patient responses. The session may be stopped if needed 236to initiate contingency interventions such as suicide intervention. The staff will restart the session 237after the contingency intervention [3]. 238 3 Empirical research on the effectiveness of behavioral activation therapy 239 A randomized, controlled, noninferiority trial conducted per NICE guidelines and by 240primary mental health practitioners in the UK showed that behavioral therapy is noninferior to 241CBT and is less expensive than CBT for the treatment of depression [34]. 242 3.1 Subjects 243 3.1.1 Depressed patients 244 Patients who regard life itself as the cause of depression respond better to cognitive 245therapy than to behavioral activation therapy, and patients who view interpersonal relationship as 246the cause of depression respond poorly to cognitive therapy [35]. For some depressed patients 247who respond poorly to cognitive therapy, self-assessment after behavioral activation intervention 248shows reduced depressive symptoms; these patients usually have severe depressive symptoms 249and lack social support, and many of them have life-long depression [36]. In addition, behavioral 250activation therapy is indicated in patients with atypical depression and chronic depression. 251Atypical depression is mainly manifested as mood responses (i.e., better response to favorable 252events), mental delays, and interpersonal withdrawal. Behavioral activation therapy is 253particularly indicated for this group of patients [37]. For patients with chronic depression who 254respond to medical treatment, social and occupational dysfunctions usually persist after medical 255intervention designed to relieve emotional symptoms and are indicated for behavioral activation 256intervention [38]. From the perspective of treatment compliance and initial treatment effects, 257behavioral activation therapy is practical and effective in improving negative symptoms [39].

12 6 13 258 3.1.2 Patients with both depression and comorbid mental disorders 259 Behavioral activation therapy improves depressive symptoms in military personnel with 260posttraumatic stress disorder (PTSD) and depression [40], pathological grief, PTSD, and 261depressive symptoms in middle-aged individuals undergoing bereavement [41], and elderly 262individuals undergoing complicated bereavement [42]. For patients with type-2 diabetes and 263depression, a novel combination of behavioral activation therapy and a fitness routine has been 264proven to improve both blood glucose and emotional symptoms [43]. The treatment reduces the 265excessive activation of the behavioral inhibition system and the excessive inhibition of the 266behavioral activation system. Moreover, the activation effect on the behavioral activation system 267is significantly stronger than that of supportive psychotherapy, and the reduction in the Beck 268Depression Inventory (BDI) score is related to an increase in the behavioral activation system 269score [44]. Behavioral activation intervention can also be used as a healthcare intervention to 270improve mild or subthreshold depressive symptoms in elderly hospitalized patients [45]. BATD 271for patients with cancer and depression in an outpatient setting improves symptoms of depression 272and anxiety, quality of life, and treatment outcomes [1]. 273 3.1.3 Military personnel with depression 274 Compared with other therapies for depression, behavioral activation therapy rarely 275considers depressed patients as weak or ill. As an action-oriented therapy, it is especially 276indicated for military personnel on active duty. Behavioral activation therapy has been 277effectively used in military populations. Extensive research has been conducted on behavioral 278activation outpatient interventions for new recruits [46], behavioral activation and therapeutic 279exposure (BA-TE) for patients with depression associated with PTSD [47], and BATD via 280electronic communications for active-duty US military service members with depression [33]. 281 3.2 Treatment modalities 282 3.2.1 Face-to-face interventions 283 Face-to-face interventions can involve either individual or group therapy. Group therapy 284is also indicated in populations with severe depressive symptoms, a history of chronic mental 285illness or physical disability, and a low employment rate [48]. In the future, studies with a larger 286sample size, before-and-after clinical outcomes, and a longer-term follow-up period should be 287conducted to investigate the long-term health outcomes of group behavioral therapy. Researchers 288have also advocated economic analyses of the cost utility of behavioral therapy. In addition, 289qualitative research can be conducted to investigate patients’ acceptance level, satisfaction, and 290treatment feedback. Such studies are still rare in Asian populations [49]. For military personnel, 291behavioral activation training has several advantages: low cost, high efficiency, high 292compatibility with the military environment (collective action), and high consistency with 293military requirements (goal-oriented). 294 3.2.2 Computerized and internet interventions 295 With the continuous development of electronic communications and its application in the 296medical and health fields, tele-mental health (TMH) or tele-behavioral health and tele-psychiatry 297are becoming important mental health models in the information age that provide mental and 298behavioral health services via electronic communications. The advantages include easier access 299to mental services, lower travel costs, no waiting, and no loss of work time. In particular, bias 300against psychotherapy may affect an individual’s willingness to actively seek psychotherapy, and

14 7 15 301home-based psychotherapy protects the privacy of and ensures a comfortable environment for 302patients [33]. 303 Specifically, in terms of cost, traditional face-to-face therapy is generally associated with 304higher economic costs and time investments. Reducing the cost of travel makes it more 305convenient for depressed patients living in the suburbs or with limited mobility to receive 306therapy [50]. Reducing economic costs reduces treatment costs for adolescents and individuals 307with a lower socioeconomic status. Reducing the time investment enables working populations 308to receive therapy without loss of work time. In terms of treatment access, currently less than 309half of individuals with mental disorders seek psychotherapy, and the rate is lower still among 310adolescents, middle-aged and elderly populations, individuals with a lower socioeconomic status, 311and minority ethnic groups. Web-based treatment improves treatment access by taking into 312consideration factors such as cost, time, travel, and privacy. In terms of effectiveness, studies 313have shown that alternative treatments, including web-based treatment, are equally effective. In 314terms of feasibility, the therapist mainly provides support and professional explanation rather 315than focusing on establishing a doctor-patient relationship. Patients who wish to establish a 316personal relationship with a therapist may call, email, or use other communication methods. In 317terms of efficacy evaluations, web-based treatments automatically collect data and even monitor 318patients’ mental health in real time. In terms of target populations, web-based psychotherapy is 319particularly suitable for adolescents, as they are generally more familiar and prefer to use the 320web-based environment and technology [51]. The development of mobile technology has made it 321possible to provide mental services and collect data at any time and from anywhere, and lower 322treatment costs and the expanded scale of services have laid the foundation for individualized 323mental health services [52]. Patient preference for psychotherapy rather than medical treatment is 324also an internal reason for the increase in web-based psychotherapy in Western countries [53]. 325With the rapid development of mobile networks and more web-based mental health resources, 326mobile psychotherapy will become a new TMH model after web-based psychotherapy. 327 Web-based behavioral activation treatment. (1) web-based behavioral activation 328therapy or integrative psychotherapy programs that include behavioral activation components. 329This includes (a) Deprexis, an integrative online treatment program that includes behavioral 330activation, cognitive reconstruction, mindfulness training and acceptance and commitment 331training, and social skills training [54]; (b) Competent Adulthood Transition With Cognitive, 332Behavioral, Humanistic, And Interpersonal Training (CATCH-IT), an internet-based program 333that includes treatment motivation interviews at enrollment and follow-ups as well as 14 web- 334based modules such as behavioral activation, cognitive behavior, and interpersonal 335psychotherapy [55]; researchers from the University of Hong Kong have incorporated the 336program into the "Grasp the Opportunity" program for adolescents in Hong Kong [56]; (c) 337internet behavioral activation (iBA) for postpartum depression [57]; (d) internet-based behavioral 338activation therapy and acceptance-based treatment [58], such as computerized cognitive 339behavioral therapy (C-CBT); (e) comprehensive psychotherapies or mental health programs that 340include behavioral activation components, such as BA-TE for depression associated with PTSD 341[59] and the community-integrated Beat the Blues (BTB) depression intervention for poor and 342at-risk populations [60]; (f) “Building a Meaningful Life Through Behavioral Activation” [3]; (g) 343an 8-week BATD with home-based tele-mental health (HBTMH) program and internet video 344conferences for active-duty US military service members [33].

16 8 17 345 Smartphone-based behavioral activation treatment. (1) smart phone-based software 346for behavioral activation therapy developed by Swedish scientists [61, 62] that includes modules 347on mental education, behavior selection and scheduling, behavior monitoring, and feedback; the 348mobile data can be uploaded to a website for background processing and feedback; (2) Mobilyze, 349smart phone-based software with hardware support developed by the Pew Research Center that 350is the first treatment software in the world for depression with real-time ecological intervention 351and the first software to use situation awareness to monitor mental health [63]. It can predict the 352patient’s mood, emotions, cognitive and motivational state, behavioral activities, and social 353context on the basis of at least 38 indexes (global positioning system, background light, recent 354calls) collected by mobile phone sensors and machine learning algorithms. The website then 355generates a feedback map based on the relationship among patient self-assessments and provides 356tutorials and tools to teach patients the concept of behavioral activation. To improve treatment 357compliance, brief calls and emails may be used to remind patients to complete assignments. 358Smart phone software focuses more on interactions with less text to read, is convenient, 359implements real-time monitoring, and is compatible with the habits of current internet users. 360 Web-based self-help therapy makes it easier for individuals to seek psychotherapy [64]. 361Thanks to its low-intensity treatment and easier access, it can be used as a prevention 362intervention for depression to reduce depressive symptoms and negative thinking in individuals 363with nonclinical depression [65]. The effect of guided self-help interventions for depressed 364patients under the community healthcare context is comparable to that of traditional face-to-face 365psychotherapy [66], In a 6- to 18-month follow-up study, the treatment effect of a guided self- 366help intervention was comparable to that of face-to-face therapy [67, 68]. Moreover, surveys 367among depressed patients have shown that patients prefer guided self-help interventions and 368psychotherapy over medical treatment [69]. As mental health models evolve and the public 369becomes more aware about psychotherapy and starts to seek more treatment, the advantages of 370behavioral activation therapy, such as low-intensity treatment and easier access, should be 371leveraged to develop prevention interventions and guided self-help intervention programs and 372promote the programs to small- and medium-sized cities, remote areas, and primary communities 373with limited public mental health services, personnel, and facilities through multiple channels 374such as internet treatment and remote treatment, in order to improve the prevention, intervention, 375and clinical treatment of depression in China. 376 For web-based treatment, the main limitation is that it cannot be easily integrated into a 377patient’s life. Although patients can carry paper materials and contact therapists via the internet, 378the actual operation is not convenient. Mobile phones are easy to carry and can monitor, record, 379and intervene when behaviors occur. In addition, web-based treatment often requires a large 380amount of text and significant reading. Mobile software is usually more user-friendly, and its 381web pages are more integrative than internet pages, which is more attractive and motivating for 382depressed patients who are prone to fatigue, thereby reducing dropouts [61]. Boschen and Casey 383summarized the advantages of using cell phones (including smart phones) for CBT: (1) 384portability; (2) social acceptance; (3) lower cost than a computer; (4) low equipment (mobile 385phone) maintenance costs; (5) a large number of mobile phone users; (6) continuous standby; (7) 386constant internet connection; (8) ability to install new applications; (9) ability to record and play 387multimedia files such as audio, photos, and videos; (10) interactive, as data can be entered via 388the keypad, touch control panel, or touch screen; and (11) designed for the general public and 389easy to use [70].

18 9 19 390 3.3 Efficacy evaluation 391 The efficacy outcomes for behavioral activation therapy include clinical outcomes such 392as the severity of symptoms and social functions; process variables such as patient satisfaction, 393treatment reliability, treatment attendance, compliance, and early dropouts; and economic 394outcomes such as cost and resource inputs [50]. 395 Clinical outcomes include behavior and social functions, which can be evaluated with the 396Cognitive-Behavioral Therapy Skills Questionnaire (CBTSQ)[71], response probability index 397(RPI)[15], and Behavioral Activation for Depression Scale (BADS)[15]. For clinical symptoms, 398conventional scales are used as per the Institute for Clinical Systems Improvement (ICSI) 399guidelines to rate clinical outcomes, as follows: remission—reduction in depressive symptoms 400by 50% or more, partial remission—reduction in depressive symptoms by 25% to 50%, and full 401remission—no depressive symptoms for at least two months. 402 Process variables: Environmental events (reinforcements) can be evaluated with the 403Pleasant Events Schedule (PES) and Unpleasant Events Schedule (UES)[10] as well as the 404Interpersonal Events Schedule (IES) and Environmental Reward Observation Scale (EROS)[15]. 405 3.4 Influencing factors 406 Factors affecting the effectiveness of behavioral activation therapy may include an 407inability to comprehend or adopt treatment principles, a lack of awareness and ability to express 408values and act according to values, poor compliance, a lack of effective compliance management 409to enhance environmental rewards, a reduction in aversive environmental events, and 410reinforcement of depression-inducing behaviors[72]. In addition, the perception of treatment 411effectiveness is related to the effectiveness of behavioral activation therapy. 412 In addition to therapy itself, patient behavior and feelings affect the effectiveness of 413behavioral activation therapy. 414 First, the ability of patients to comprehend or adopt treatment principles affects treatment 415effectiveness. For example, patients who do not understand their own values or cannot express 416their values are unable to act according to their values[72], which affects the effectiveness of 417treatment. 418 Second, patient compliance affects treatment effectiveness. Treatment compliance plays a 419larger role in the effectiveness of treatment than does the amount of activities completed[73]. 420Patients with poor compliance often cannot effectively self-manage behaviors to ensure 421enhanced compliance, a necessary condition to enhance exposure to environmental rewards and 422reduce exposure to aversive or depression-inducing events in the environment[72]. In contrast, 423web-based data are more relevant to a patient, which ensures high treatment compliance when 424the data meet the patient’s specific needs. Moreover, modular treatment can also be adopted, 425allowing patients to choose any treatment module as needed, which improves treatment 426acceptance[74]. 427 Third, the focus of a patient on the treatment effect (effective or ineffective) affects the 428effectiveness of treatment. If the patient perceives that the treatment is helpful, behavioral 429activation intervention is usually more effective. If the therapist only tries to identify the cause of 430depression with the behavioral activation model, behavioral activation intervention will be less 431effective[35].

20 10 21 432 Last, the interpretation by patients about their depression affects the effectiveness of 433behavioral activation therapy. For example, if a patient interprets depression as the meaning of 434their own existence, cognitive therapy is usually more effective while behavioral activation 435therapy is usually less effective. If a patient interprets depression as a result of relationships, 436cognitive therapy is usually less effective [35]. An individual’s cognitive tendency such as 437negative bias is a better predictor of his/her response to behavioral activation therapy than is 438positive compensation [75]. 439 3.5 Comparison with other therapies for depression 440 (1) Behavioral activation therapy versus medical treatment. For patients with severe 441depression, the effect of behavioral activation therapy is comparable to that of antidepressants, as 442demonstrated in a randomized placebo-controlled trial, and both treatments are superior to 443cognitive therapy [76]. Moreover, behavioral activation therapy has a low risk of relapse and 444recurrence, considerably low cost and no drug-related risks [77]. A study in Chinese depressed 445patients showed that behavioral activation therapy combined with medical treatment was 446superior to medical treatment alone [78], suggesting that behavioral activation therapy can be 447used as an adjuvant therapy to medical treatment to improve long-term efficacy and prevent 448relapse. 449 (2) Behavioral activation therapy versus cognitive therapy. Both behavioral activation 450therapy and cognitive therapy have long-lasting effects, are less expensive than medical 451treatment, and are suitable for long-term use [79]. Behavioral activation therapy is more effective 452than is cognitive therapy for reducing the drop-out rate. It is a good option for patients who do 453not respond to cognitive therapy or CBT, especially for patients with severe lifetime illness, 454patients who abuse drugs, and patients with early dementia with severe depression [77]. For 455patients with moderate to severe depression, behavioral activation therapy is more effective than 456cognitive therapy [36]. In addition, behavioral activation therapy helps improve negative 457cognition, reduces negative reflection, and promotes cognitive reconstruction, with no need for 458cognition-based interventions [80]. Behavioral activation therapy improves cognitive activity, 459reduces negative reflection, and promotes cognitive restructuring. It is easier to implement, 460requires fewer sessions, and has a lower treatment intensity than does comprehensive CBT. 461 (3) Behavioral activation therapy versus problem-solving therapy [81, 82]. Both therapies 462are action-oriented, but behavioral activation therapy focuses more on increasing behavioral 463activities with positive reinforcement, whereas problem-solving therapy focuses more on 464obtaining behavioral skills and solving problems. The combination of these two therapies can 465significantly improve the treatment outcomes of individuals with subthreshold depression [83]. 466 (4) Behavioral activation therapy versus mindfulness-based therapy. Behavioral 467activation therapy emphasizes focused activation rather than simply scheduling activities in a 468random manner. The goal is to identify behaviors and activities with positive reinforcement and 469focus on the activity that he/she is currently participating in (such as paying attention to color, 470noise, and smell during the activity). The focus on experience is very similar to that of 471mindfulness training. However, behavioral activation therapy is more suitable for severe 472depressive symptoms, whereas mindfulness training is more suitable for mild depressive 473symptoms [84]. 474 (5) Behavioral activation therapy versus acceptance and commitment therapy. Both 475therapies include life goals and values as treatment components [58]. Behavioral activation

22 11 23 476therapy is more comprehensive and treatment-oriented as it includes motivation-related value 477components and defusion techniques to deal with negative thinking. 478 (6) Behavioral activation therapy versus existentialism and psychological dynamics. The 479combination of these therapies helps individuals improve his/her understanding of his/her 480inherent complexity, enhance self-function, create an embracing environment, and enhance the 481sense of responsibility through individual autonomy, thereby promoting a sense of transcendence 482[85]. 483 In general, behavioral activation therapy emphasizes behavioral changes and its 484contextual factors and is effective for negative symptoms, making it an effective therapy for 485preventing depression and relapse. As behavioral activation therapy draws on the effective 486treatment components of other treatment modalities and becomes a more comprehensive 487modality, it may play a greater role in psychotherapy for simple depression and depression 488associated with physical disorders. 489 4 Directions of future research 490 To date, no systematic studies on the mechanism and application of behavioral activation 491therapy have been conducted in China, and a standard treatment manual has been lacking. Future 492research should take into account the following considerations: 493 4.1 Neural mechanisms of BA 494 Based on the assumption that insufficient or loss of positive reinforcement (reward) leads 495to and sustains depressive symptoms. Theoretically, behavioral activation therapy focuses on 496improving goal-directed behaviors, increases exposure to positive reinforcement (rewards) in the 497environment, enhances happy experiences, and reduces depressive symptoms. However, it is 498unclear how reward brain networks (e.g. dopamine pathways) are modulated by behavioral 499activation therapy. Indirect evidence showed that BA increases the activation intensity of the 500caudate during the stage of expected rewards, the activation intensity of the putamen during the 501stage of action selection, and the activation intensity of the mOFC and DLPFC during the stage 502of reward feedback in depressed patients [19]. Future research needs to further clarify the 503neurobiological mechanism of how behavioral activation therapy regulates the reward network, 504and how these changes may be correlated with other emotion and cognition brain networks 505which are commonly impaired in depressed patients. 506 4.2 Prediction of treatment decision and outcome 507 Activity scheduling is among the most critical components of behavioral activation 508therapy. The types of activities and how these activities are connected to patient values and life 509goals are important considerations when developing a treatment plan suitable to a patient’s 510cultural background and specific needs. Patient compliance can be improved and dropouts can be 511reduced via signed treatment protocols and weekly emails or phone follow-ups. In addition, 512patient compliance can be improved by providing treatment-related internet resources based on 513individual needs [74]. Machine learning can be used to make predictions of treatment outcome 514from high-dimensional data of neural changes underlying BA treatment [86], which may provide 515new insights into the pathophysiology of depression and guidance towards more individualized 516treatment decision [87, 88]. In addition, modular treatment plans can be developed to allow 517patients to choose treatment plan(s) according to their own needs and the needs of different 518treatment stages [89].

24 12 25 519 4.3 Symptom monitoring and efficacy evaluation 520 Enhanced sensitivity is a stable personality trait. Even for clinical populations undergoing 521psychotherapy, enhanced sensitivity can predict posttreatment emotional symptoms after 522considering the initial symptoms [90]. Therefore, enhanced sensitivity can be used as an 523evaluation measure for treatment outcomes. Second, given the heterogeneity of depressive 524symptoms which involve the intertwined emotional, motivational and cognitive neural networks, 525it is not appropriate to rely solely on improvement of mood symptoms as measures for efficacy 526evaluation and monitoring. Motivational system symptoms and treatment outcomes should be 527more accurately evaluated by incorporating motivation measures such as the behavioral 528inhibition/activation system (BIS/BAS) scale [91]. 529 4.4 Cost-effectiveness in delivery of mental health services 530 In China, mental health literacy has been increasingly emphasized in the last decade [92- 53195]. There seems to be an urgent need to enhance public awareness to seek help for mental health 532services. One main factor may be accessibility of public mental health services and the treatment 533cost of mental disorders. The development of tele-mental health interventions (e.g. web-based, 534smartphone-based or telephone-delivered) may be promising to increase the cost-effectiveness of 535BA [96, 97], which may provide accessible services to those who have difficulty seek for 536traditional face-to-face intervention. 537 Acknowledgements 538 This research was financially supported by the Youth Cultivation Foundation of Medical 539Science in Army Medical University (2016XPY08), the National Youth Cultivation Foundation 540of Military Medical Science (17QNP002), and the Chongqing Social Science Planning Project 541(2017QNSH21). 542 Author Contributions Statement 543 X W and Z F conceived of the presented design of the study. X W collected literatures, 544reviewed relevant researches and drafted the manuscript in consultation with Z F. 545 546 XReferences: 547 [1]. Hopko, D.R., et al., Cognitive-behavior therapy for depressed cancer patients in a medical care setting. 548Behav Ther, 2008. 39(2): p. 126-36. 549 [2]. Jacobson, N.S., et al., A component analysis of cognitive-behavioral treatment for depression. J Consult 550Clin Psychol, 1996. 64(2): p. 295-304. 551 [3]. Spates, C.R., et al., Initial Open Trial of a Computerized Behavioral Activation Treatment for Depression. 552Behavior Modification, 2012. 37(3): p. 259-297. 553 [4]. Lewinsohn, P.M. and J. Libet, Pleasant events, activity schedules, and depressions. J Abnorm Psychol, 5541972. 79(3): p. 291-5. 555 [5]. Rehm, L.P., N.J. Kaslow and A.S. Rabin, Cognitive and behavioral targets in a self-control therapy 556program for depression. J Consult Clin Psychol, 1987. 55(1): p. 60-7. 557 [6]. Hollon, S.D. and J. Garber, Cognitive Therapy for Depression: A Social Cognitive Perspective. Personality 558and Social Psychology Bulletin, 1990. 16(1): p. 58 -73. 559 [7]. Jacobson, N.S., C.R. Martell and S. Dimidjian, Behavioral Activation Treatment for Depression: Returning 560to Contextual Roots. Clinical Psychology: Science and Practice, 2001. 8(3): p. 255-270. 561 [8]. Dickinson, A., Actions and Habits: The Development of Behavioural Autonomy. Philosophical 562Transactions of the Royal Society of London, 1985. 308(1135): p. 67-78. 563 [9]. Huston, J.P., et al., Animal models of extinction-induced depression: loss of reward and its consequences.

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