Physical Activity, Physical Fitness, and Depression

Physical Activity, Physical Fitness, and Depression

Oxford Research Encyclopedia of Psychology Physical Activity, Physical Fitness, and Depression Felipe B. Schuch and Brendon Stubbs Subject: Clinical Psychology: Disorders and Therapies, Sport Psychology Online Publication Date: Oct 2017 DOI: 10.1093/acrefore/9780190236557.013.201

Summary and Keywords Depression is a leading cause of global burden affecting people across all ages, genders, and socioeconomic groups. Antidepressants are the cornerstone of treatment, yet treatment response is often inadequate. While some psychological interventions such as cognitive behavioral therapy can also help alleviate depressive symptoms, alternative and complimentary treatment options are required. In particular, therapeutic interventions that also address the greatly increased levels of obesity and cardiovascular disease among people with depression may offer added value. With the rising burden of premature mortality due to cardiovascular disease in people with depression and promising evidence base for physical activity to improve depressive symptoms, it is important to review the role, benefits, and underlying neurobiological responses of exercise among people with depression.

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Physical Activity, Physical Fitness, and Depression There has been a growing body of evidence to suggest that higher levels of physical activity reduce a person’s risk of incident depression. It appears that lower levels of cardiorespiratory fitness increase an individual risk of depression, suggesting that physical activity and physical fitness have a key role in the prevention of depression. Moreover, exercise can improve depressive symptoms in those with subthreshold depressive symptoms and major depressive disorder. Despite the effectiveness of exercise, the optimal dose and frequency are yet to be fully elucidated. Nonetheless, exercise appears to be well accepted by people with depression, with relatively low levels of dropout from interventions, particularly when supervised by qualified professionals with expertise in exercise prescription. Various barriers to engaging in exercise exist and motivational strategies are essential to initiate and maintain exercise. A number of hypotheses have been postulated to determine the antidepressant effect of exercise; however, most are based on animal models or models elucidated from people without depression. Therefore, future representative research is required to elucidate the neurobiological antidepressant response from exercise in people with depression. Physical activity interventions targeting fitness should be a central part of the prevention and management of depression. In particular, physical activity interventions offer a viable option to prevent and address cardiometabolic abnormalities and cardiovascular disease, which account for a significant amount of premature deaths in this population and are not addressed by standard pharmacological and psychological therapies. Keywords: depression, major depressive disorder, physical activity, exercise, fitness, health promotion

Introduction Major depressive disorder (MDD) is a leading global cause of burden across the world and is ranked in the top ten causes of years lived with disability (Murray et al., 2012; Vos et al., 2012). The global prevalence of MDD is between 6 and 20% (Andrade et al., 2003). In addition, the prevalence of subthreshold depressive symptoms, which do not quite meet the criteria for a formal diagnosis of MDD, is approximately 15–20% (Ayuso-Mateos et al., 2001). However, both MDD and depressive symptoms are associated with considerable burden to the individual (Charlson, Diminic, Lund, Degenhardt, & Whiteford, 2014; Ferrari et al., 2013) and society more widely, with rising economic costs associated with the care of people with depression (Chisholm et al., 2016). Consequently, the World Health Organization (WHO) and many individual countries have developed policies to prevent and manage depression. While the primary symptoms of depression involve low mood, including loss of interest and decreased motivation, there is increasing evidence that depression is also associated with a considerable increased risk of various physical health comorbidities (Moussavi et al., 2007). Of particular concern are the increased levels of high levels of cardiometabolic disease (Vancampfort, Stubbs, Mitchell et al., 2015) and diabetes (Vancampfort et al., Page 2 of 27


Physical Activity, Physical Fitness, and Depression 2016). While suicide accounts for some of the premature deaths among people with depression, it is well established that the high levels of cardiovascular and metabolic disease are leading contributors to the premature mortality gap of approximately 15 years compared to the general population (Charlson et al., 2014). In the general population, there is a plethora of evidence that physical activity interventions are broadly effective in preventing and managing cardiovascular disease and associated mortality (Naci & Ioannidis, 2013). Despite this acknowledgement, physical activity still appears to be low priority in clinical practice for people with depression and is not yet established as a treatment of equitable value to the more dominant paradigms such as pharmacotherapy and psychotherapies. The aims here are to: • Clarify the relationship between physical activity, sedentary behavior, and depression, • Review the potential role of cardiorespiratory fitness and depression, • Review the benefits for exercise as a treatment for depression, • Review factors influencing physical activity participation and maximizing participation, and • Consider how to prescribe exercise in depression.

Defining Physical Activity and Exercise Physical activity is a broad concept, defined as “Any bodily movement produced by skeletal muscles that results in energy expenditure” (Caspersen, Powell, & Christenson, 1985) that can be done in different contexts and with different aims such as leisure time activities, activities for transportation, housework or gardening, and work-related activities (Craig et al., 2003). Interestingly, the context related to the physical activity is important in people with depression, because previous literature has demonstrated that leisure time activities have a stronger inverse association with depressive symptoms in women (Teychenne, Ball, & Salmon, 2008) and in older persons (Joshi et al., 2016) than transportation, work, or housework or gardening activities. Exercise is itself a subset of physical activity, defined as planned, structured, and repetitive and has as a final or an intermediate objective the improvement or maintenance of physical fitness (Caspersen et al., 1985).

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Physical Activity, Physical Fitness, and Depression A body of evidence supports the notion that physical activity and depression are intimately related in a bidirectional relationship. In the general population, crosssectional studies have shown that “healthy people” without depression who demonstrated lower physical activity levels have a higher risk of presenting with depressive symptoms. This is a relationship that has been demonstrated across various different cultures and countries. For instance, in a population study conducted in Norway, men and women engaged in higher physical activity had a 37% and 31%, respectively, lower risk of having increased depressive symptoms (Augestad, Slettemoen, & Flanders, 2008). In South America, a study found that Brazilians who did not regularly engage in physical activity were two times more likely to present with increased depressive symptoms than those who are very active (De Mello et al., 2013). In Asia, a Korean study reported a 48% increased prevalence of depressive symptoms in people who were not regularly involved in vigorous activities when compared with those who were engaged in any regular activity. The relationship between low levels of physical activity and depression is evident across the age spectrum. Children with increased levels of physical activity are at a 38% decreased risk of presenting higher levels of depressive symptoms (Kremer et al., 2014). Moreover, another study found that older people with lower levels of physical activity were at an 83% increased risk of developing depressive symptoms, compared to their more active counterparts (Paulo et al., 2016). The literature considering the influence of physical activity levels on future depression was summarized by Mammen and Faulkner (Mammen & Faulkner, 2013). The authors conducted a systematic review and established across 30 longitudinal studies that 25 demonstrated an inverse relationship between high physical activity and lower risk of incident depression or vice versa. Therefore, one can say with reasonable confidence that there is considerable evidence suggesting that physical activity offers a protective effect for the risk of developing depression in people without any evidence of depression. However, of note, some of the papers included in the Mammen and Faulkner review have found that the protective effect of physical activity is limited to women (Carroll, Blanck, Serdula, & Brown, 2010; Farmer et al., 1988; Mikkelsen et al., 2010; Wang et al., 2011). While the results of this narrative review are compelling, a meta-analysis is required to evaluate the consistency of the findings across all included studies. Moreover, a meta regression analysis would enable the exploration of potential predictors (e.g., mean age, gender) that might moderate or mediate this relationship. Lastly, a number of studies have suggested that increasing physical activity may reduce the risk of future depressive episodes (Gudmundsson et al., 2015) and one has shown that higher physical activity levels predict better response to cognitive behavioral therapy (Hallgren, Helgadóttir et al., 2016). While the results to date are encouraging, one should note that the data are observational and future randomized control trials (RCTs) should seek to prescribe physical activity among people at risk for depression to see if such a program can actually prevent a depressive episode. Only at such a time will questions around causality be addressed. Again, a meta-analysis can help to clarify whether Page 4 of 27


Physical Activity, Physical Fitness, and Depression different physical activities (e.g., types, intensities, volumes) provide different protective effects. In addition, meta-regression analyses should investigate the magnitude of the protective effects of different physical activities on depression. At the opposite end of the physical activity spectrum is sedentary behavior. Sedentary behavior is defined as any waking behavior characterized by an energy expenditure ≤1.5 metabolic equivalents (METs) while in a sitting or reclining posture (Bailey et al., 2015). There is an abundance of evidence in the general medical literature demonstrating that higher levels of sedentary behavior are associated with an increased risk of cardiovascular disease, diabetes, and premature mortality (Biswas et al., 2015). When one considers that these are the leading causes of premature mortality in people with depression, understanding and preventing excessive sedentary behavior is critical. Moreover, research has demonstrated that higher levels of sedentary behavior are also associated with an increased risk of depressive episodes in 15 months (Tsutsumimoto et al., 2017). The study revealed that individuals who spent 480 minutes or more per day in sedentary activities were at 63% increased risk of being depressed in 15 months when compared to individuals who spent 240 minutes or less per day in sedentary activities. A meta-analysis (Zhai, Zhang, & Zhang, 2015) found that higher levels of sedentary behavior are also associated with an increased risk of incident depression. While the exact pathway between sedentary behavior and depressed mood is not yet fully elucidated, a randomized study did offer some insight (Endrighi, Steptoe, & Hamer, 2016). The authors (Endrighi et al., 2016) assigned the intervention arm to enforced sedentary behavior in healthy control subjects and demonstrated that mood changes were evident, which was underpinned by a stress response and increase in IL-6. While this psychobiological paper offered some insight into the potential pathway from sedentary behavior to lower mood, one should note that clearly more research is required to further elucidate this relationship. Despite the potential hazards of sedentary behavior, engaging in physical activity can be difficult for people with major depressive disorder (MDD), and many studies have demonstrated that people with MDD are significantly less active compared to healthy controls (Helgadóttir, Forsell, & Ekblom, 2015). In particular, people with MDD spend less time in light, moderate, vigorous, and overall activity when compared to people without MDD diagnosis (Helgadóttir et al., 2015; Wielopolski et al., 2015). Also, people with MDD spend more time involved in sedentary behavior (Sanchez-Villegas et al., 2008). Perhaps unsurprisingly, the proportion of depressed people who do not complete the minimum recommended time of 150 minutes per week of physical activities (PA) is often high and less than the general population. While some variations exists in different cultures, ages, genders, and settings, the proportion meeting the recommend 150 minutes of moderate to vigorous PA per week ranges from 14.4% to 88% (Correia & Ravasco, 2014; Da Ronch et al., 2015; Schuch et al., 2017).

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Factors That May Influence Physical Activity in People With Depression There are several factors that may contribute to the lower physical activity levels in people with depression. Obviously, given the nature of the depression, some of the core symptoms include de-motivation, fatigue, low energy, low self-esteem, and apathy, which are barriers to exercise (Seime & Vickers, 2006). This notion is supported by Vancampfort, Stubbs, Sienaert et al. (2015), who systematically reviewed studies assessing the potential correlates of physical activity participation in people with depression. Vancampfort, Stubbs, Sienaert et al. (2015) confirmed that the severity of depressive symptoms and lower self-efficacy were inversely correlated to physical activity levels. Despite the severity of depressive symptoms that have been demonstrated as a correlate of physical activity in people with depression, Vancampfort, Stubbs, Sienaert et al. (2015) identified that other biological factors, such as body mass index (BMI) and the presence of clinical comorbidity, were also correlated with lower physical activity levels. Moreover, other demographic (e.g., ethnicity), biological (e.g., physical performance, psychomotor agitation, and use of anxiolytic medication), and psychological, cognitive, and emotional (e.g., positive and negative affect, cognitive functioning, quality of life on physical domain, lack of knowledge of the importance of exercise, fear and negative experiences, and others) factors may serve as barriers or facilitators to physical activity in people with depression. Given these factors, clearly clinicians and researchers need to be aware of the potential barriers and facilitators and seek to address these where appropriate.

Depression and Cardiorespiratory Fitness Recently, there has been a growing interest in the importance of good cardiorespiratory health on various health outcomes. Cardiorespiratory fitness (CRF), the ability of the circulatory and respiratory systems to supply oxygen to working muscles during sustained physical activity, typically expressed as mlO2*kg−1*min−1) is often used as a proxy, or an objective measure of physical activity (Lee, Artero, Sui, & Blair, 2010). Indeed, cardiorespiratory fitness is strongly influence by physical activity levels (Lee et al., 2010). However, CRF is determined by several other physiological and anatomical factors such as, but not limited to, the maximal cardiac output, pulmonary diffusing capacity, and mitochondrial enzyme levels (Bassett & Howley, 2000). Cardiorespiratory fitness is an independent predictor of cardiovascular disease and allcause mortality (Lee et al., 2010), being independent of age, ethnicity, adiposity, smoking status, alcohol intake, and health conditions (Lee et al., 2010). In a systematic review by Kodama et al. (2009), each 1-MET increment in CRF represented a reduction of 13% and Page 6 of 27


Physical Activity, Physical Fitness, and Depression 15% of all-cause mortality and cardiovascular disease (CVD) events, respectively. In addition, evidence suggests that cardiorespiratory fitness has a greater predictive value to cardiovascular disease and all-cause mortality than physical activity (PA) (Myers et al., 2004). People with depression have decreased cardiorespiratory fitness when compared to nondepressed people (Boettger et al., 2010; Kiive, Maaroos, Shlik, Tõru, & Harro, 2004). Donath et al., (2010) compared the ventilatory parameters of people with major depressive disorder (MDD) to matched people without the diagnosis of depression and found that participants with MDD had a decreased aerobic capacity, an increased VE/ VCO2-slope and an inverse relationship between VE/VCO2-slope and peak VO2. These results indicate that depressed patients need to ventilate more than non-depressed people to a given amount of developing CO2, suggesting an impaired ventilatory efficiency in MDD. There is an association between cardiorespiratory fitness and depressive symptoms. The negative relationship between depressive symptoms and cardiorespiratory fitness appears to be moderate, occurring both in people with and without a formal diagnosis of MDD (Papasavvas, Bonow, Alhashemi, & Micklewright, 2016).

Cardiorespiratory Fitness to Prevent Depression There is emerging evidence to support the notion that cardiorespiratory capacity is a protective factor for depression. Sui et al. (2009) evaluated the association between cardiorespiratory fitness and the diagnosis of depression in the Aerobics Center Longitudinal Study (ACLS), including 11,285 men and 3,085 women who were primarily self-referred or sent by their employer for preventive medical examinations. Participants were followed up an average of 12 years; the authors established the odds of reporting depressive symptoms were 51% and 54% higher for men and women with low CRF compared to men and women with higher CRF, respectively. This result was supported by a subsequent study by Åberg et al. (2012) that evaluated the CRF of a cohort of Swedish conscripted men. Depression was evaluated using the Swedish National Hospital Discharge Register, which covers virtually all inpatient care for psychiatric disorders. During a follow-up period that ranged from 3 to 40 years, men with lower CRF presented a 96% increased risk of a serious depressive episode. Lastly, one study in middle school adolescents (boys and girls, average age 11 years) evaluated the association between cardiorespiratory fitness and depressive symptoms. The cardiorespiratory fitness of girls was inversely associated with the severity of depressive symptoms in the period of one year. The same tendency occurred with boys;

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Physical Activity, Physical Fitness, and Depression however, the association was not statistically significant (Ruggero, Petrie, Sheinbein, Greenleaf, & Martin, 2015). Declines in cardiorespiratory fitness are expected with advancing age. However, people who maintain their cardiorespiratory fitness across the lifespan remain at a decreased risk of experiencing a depressive episode, while decreases on cardiorespiratory fitness are prognostic of increases on the risk of depressive episodes (Dishman et al., 2012). Therefore, the emerging literature suggests that maintaining cardiorespiratory fitness could be an important protective factor for various important health outcomes including prevention of depression.

Exercise as a Treatment for Depression The potential benefits of exercise for depression have been on the radar since the 1970s. Some of the first studies to investigate the effects of exercise in people with depression that are evaluable at PubMed were published in the 1970s: Brown, Ramirez, and Taub (1978) and Greist et al. (1979); they were followed by several studies of Egil Martinsen, including but not limited to Martinsen, 1987; Martinsen, Hoffart, and Solberg, 1989; and Martinsen, Medhus, and Sandvik, 1985 in the eighties. Despite being a topic of interest for a long time, the potential benefits of exercise for depression remain topical and controversial (Schuch & de Almeida Fleck, 2013; Schuch, Morres, Ekkekakis, Rosenbaum, & Stubbs, 2017). Current guidelines propose the inclusion of exercise as a treatment for depression based on meta-analytical findings (Cleare et al., 2015; Malhi et al., 2015). Indeed, several meta-analyses support a positive effect of exercise on depression (Cooney et al., 2013; Josefsson, Lindwall, & Archer, 2014; Rethorst, Wipfli, & Landers, 2009; Silveira et al., 2013). However, the results and magnitude of effect size appear highly sensitive depending on the inclusion criteria used and which studies are included in the analyses. For example, several meta-analyses found effects sizes (ES) with a magnitude ranging from −0.53 (medium effect size) to −1.39 (large effect size) standardized mean deviations supporting antidepressant effects of exercise in children, adults and older adults with depression (Bridle, Spanjers, Patel, Atherton, & Lamb, 2012; Carter, Morres, Meade, & Callaghan, 2016; Craft & Landers, 1998; Josefsson et al., 2014; North, McCullagh, & Tran, 1990; Rethorst et al., 2009; Silveira et al., 2013; Stathopoulou, Powers, Berry, Smits, & Otto, 2006). On the other hand, some meta-analyses (Krogh, Nordentoft, Sterne, & Lawlor, 2011; Lawlor & Hopker, 2001) failed to find significant antidepressant effects of exercise. This discrepancy has somewhat confused key stakeholders, but a meta-analysis (Stubbs, Vancampfort, Rosenbaum, Ward, Richards, Ussher et al., 2016) demonstrated that control groups in exercise and depression studies experience large ES improvement in depressive symptoms, beyond that reported in antidepressant studies and what one would expect from regression to the mean.

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Physical Activity, Physical Fitness, and Depression In the 2013 updated version of the Cochrane meta-analysis entitled “Exercise for Depression” (Cooney et al., 2013) the authors concluded that “Exercise is moderately more effective than a control intervention for reducing symptoms of depression, but analysis of methodologically robust trials only shows a smaller effect in favour of exercise,” a statement that added more fuel to the discussion. The effect sizes identified were −0.62 for all trials and −0.18 for “high-quality trials only.” The effect was not statistically significant for high-quality trials only. Interestingly, the methods used in this meta-analysis were the aim of criticisms due to, among other issues, the problematic inclusion and exclusion criteria applied (Ekkekakis, 2015). For example, the Cochrane review included studies that compared exercise versus pharmacological antidepressants (Blumenthal et al., 1999), and exercise versus exercise (Krogh, Saltin, Gluud, & Nordentoft, 2009; Krogh, Videbech, Thomsen, Gluud, & Nordentoft, 2012). The inclusion of those studies decreased the magnitude of the effect of exercise because the control groups had a large improvement in depressive symptoms (Stubbs, Vancampfort, Rosenbaum, Ward, Richards, Ussher et al., 2016). These issues were addressed in a metaanalysis (Schuch, Vancampfort, Richards, Rosenbaum, Ward, & Stubbs et al., 2016) which only included trials with a non-active control group (i.e., fair comparator), and the updated effect was equal to −0.98 for all studies and −0.88 for high-quality trials. The review also identified a publication bias, leading to the underestimation of the effects in the literature. Correcting for publication bias, the new ES were −1.11 and −1.21 for all trials and high-quality trials only, respectively. In this meta-analysis, aerobic exercise demonstrated greater efficacy. Also, supervision of the exercise sessions by exercise professionals was associated with greater improvements. Exercise can be used as a treatment for depression across the lifespan. A meta-analysis demonstrated that exercise is effective for the treatment of depression in adolescents (Carter et al., 2016). In people older than 60 years, another meta-analysis demonstrated that exercise is effective in decreasing the depressive symptoms with an effect size of −0.90 (large effect size) (Schuch, Vancampfort, Rosenbaum, Richards, Ward, Veronese et al., 2016). The authors found that exercise performed in group format, with mixed supervised and non-supervised format, have greater effects. However, older people with other clinical comorbidities experienced less benefit from exercise.

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Maximizing Physical Activity Participation and Preventing Dropouts Despite the benefits of physical activity, treatment dropout and adherence poses important challenges and can negatively affect treatment outcomes. In order to try to understand how common dropouts from exercise is in depression Stubbs, Vancampfort, Rosenbaum, Ward, Richards, Soundy et al. (2016) conducted a meta analysis to establish what may influence physical activity (PA) treatment dropout. Overall, the authors established that the pooled dropout rate from exercise across 40 randomized control trials (RCTs) was 18.1% (95%CI = 15.0–21.8%) and 17.2% (95%CI = 13.5–21.7, N = 31) in people with depression. When considering factors influencing dropout from exercise, meta regression analyses revealed that higher baseline depressive symptoms (β = 0.0409, 95%CI = 0.0809–0.0009, P = 0.04) predicted greater dropout, while supervised interventions delivered by physiotherapists (β = −1.2029, 95%CI = −2.0967 to −0.3091, p = 0.008) and exercise physiologists (β = −1.3396, 95%CI = −2.4478 to −0.2313, p = 0.01) predicted lower dropout. Of interest, dropout rates in exercise studies were actually lower than in control conditions (OR = 0.642, 95%CI = 0.43–0.95, p = 0.02), therefore suggesting that exercise is an acceptable form of treatment for people with depression. However, the results also highlight that among those with more pronounced depressive symptoms, professional supervision may help keep engagement in exercise so that the individual is then able to gain from the known benefits of exercise. Equally relevant, the low adherence remains a challenge in trials with people with depression. For example, in the DEMO I trial, the participants performed about half of the strength and aerobic exercise sessions (Krogh, Saltin, Gluud, & Nordentoft, 2009). There are, however, a paucity of studies investigating the correlates or predictors of low adherence.

Comparing Physical Exercise With Other Treatments While exercise should form part of an overall multimodal treatment package for people with depression, comparing the potential benefits of exercise versus other treatments can help place some context on the relative effectiveness of exercise. Some studies have compared the effectiveness of exercise to standardized treatments such as pharmacological antidepressants. In the first study of its kind (Blumenthal et al., 1999), the rate of participants who improved significantly from depression following four months of intervention was not different in the exercise group (60.4%) when compared to the participants in the antidepressant sertraline group (68.8%). In a second study, Blumenthal et al. (2007) compared home-based exercise, supervised exercise, and Page 10 of 27


Physical Activity, Physical Fitness, and Depression sertraline over 16 weeks. Again, at the end of the intervention, no significant differences were found between the exercise groups and the sertraline group. Interestingly, the participants of the first study from Blumenthal were followed for 10 months. At the end of this period, more than 85% of participants of the exercise group remained recovered versus about to 60% of participants of the sertraline group (Babyak et al., 2000). The benefits of exercise also appear comparable to common psychotherapies. A previous Cochrane review by Cooney et al. (2013) compared the effects of exercise to psychological therapies. The analysis including seven studies demonstrated that the effect of exercise is not different from psychotherapies. These results are supported by a large clinical trial that involved 946 participants conducted by Hallgren et al. (2015), showing that exercise has similar effects of Internet-based cognitive therapy. Interestingly, in this large and well conducted clinical trial, the benefits of exercise were maintained 12 months after treatment (Hallgren, Helgadóttir et al., 2016). Exercise has also previously been compared with electroconvulsive therapy (ECT) and chronotherapeutic intervention (wake and light therapy). Salehi et al. (2014) have found that exercise was similarly efficacious when compared to ECT among treatment-resistant depressed patients. However, a chronotherapeutic intervention based on keeping the participant awake three nights per week, and light exposure at the following morning achieved greater improvement in depressive symptoms compared to home-based exercise (Martiny et al., 2012).

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Other Benefits of Exercise To focus purely on the antidepressant influence of exercise would be a great injustice, given the multitude of other health and well-being benefits of physical activity and exercise. As previously outlined, people with depression are at greatly elevated risk of premature mortality due to cardiovascular-related deaths. Unlike antidepressants, which may actually increase a person’s risk of cardiovascular disease (Correll, Detraux, De Lepeleire, & De Hert, 2015), exercise has the potential to reduce this risk. In the general population there is a plethora of evidence that exercise is broadly as effective as pharmacological interventions in prevention of cardiovascular disease and deaths (Naci & Ioannidis, 2013). While the literature is still growing in people with depression, there is promising evidence that exercise can improve cardiorespiratory fitness in this patient group, a better predictor of mortality than body mass index (Barry et al., 2014). Specifically Stubbs, Rosenbaum, Vancampfort, Ward, and Schuch, 2016 found that aerobic exercise increased cardiorespiratory fitness (Hedge’s g = 0.64, 95%CI = 0.32– 0.96, p