Physical activity and depression: Towards understanding the antidepressant mechanisms of physical activity

Highlights

• Engaging in physical activity can reduce depressive symptoms.

• Exercise stimulates several neuroplastic processes implicated in depression.

• It also reduces inflammation and increases resilience to oxidative and physiological stress.

• Exercise promotes self-esteem, social support and self-efficacy.

• Understanding these mechanisms can improve the design of exercise interventions and maximise treatment response.

Abstract

Physical activity can treat and prevent depressive symptoms, but its antidepressant mechanisms are yet to be established. In this review, we comprehensively assess key biological and psychosocial mechanisms through which physical activity exerts antidepressant effects, with a particular focus on exercise.

Exercise, a subset of physical activity, influences a range of biological and psychosocial processes also implicated in the pathophysiology of depression. We focus on the capacity for exercise to elicit changes in neuroplasticity, inflammation, oxidative stress, the endocrine system, self-esteem, social support and self-efficacy. We also discuss how a better understanding of these mechanisms can inform the way we design and implement exercise-based interventions to maximise their antidepressant effects on an individual basis. We conclude by presenting a conceptual framework of the key biological and psychosocial mechanisms underlying the relationship between physical activity and depressive symptoms, and the moderators and confounders that may influence it.

Introduction

Depression is a common mental health disorder that can have a major impact on individual wellbeing and daily functioning (Kessler, 2012). According to the World Health Organization, depression affects around 300 million people and is now the leading cause of disability worldwide (WHO, 2017). Depression is characterised by persistent low mood, dysphoria, impaired motivation and several other symptoms, ranging from psychomotor to cognitive impairments (American Psychiatric Association, 2013). Depression is also associated with serious physical health comorbidities including cardiovascular disease (Correll et al., 2017; Hare et al., 2014), metabolic risk factors such as adiposity (Capuron et al., 2017), premature mortality (Correll et al., 2017; Walker et al., 2015) and a large financial cost to society (Chisholm et al., 2016). The treatment and prevention of depression remains a public health priority (Cuijpers et al., 2012; Jorm et al., 2017).

Depression is a complex condition, its heterogeneity exemplified by the fact that two people can be diagnosed with depression and not share a single symptom (Fried and Nesse, 2015). This poses considerable challenges for traditional treatments, which include pharmacotherapy, psychotherapy, or a combination of both. These forms of therapy have provided invaluable benefits for the treatment of depression. For example, the widespread use of antidepressant medications demonstrates their scalability and accessibility (Kantor et al., 2015). Treatment effects tend to be small-to-modest for pharmacotherapy (Cipriani et al., 2018) and psychotherapy (Cuijpers et al., 2019), with a third of people with depression remaining non-responsive to treatment (Rush et al., 2006). Pharmacotherapy can also cause several adverse side-effects, such as headaches and nausea (Anderson et al., 2012). A substantial minority of people with depression do not seek treatment at all (Hasin et al., 2018). Pharmacotherapy and psychotherapy are also unable to address the physical comorbidities associated with depression (Correll et al., 2017). Both pharmacotherapy and psychotherapy will continue to play an important role in the treatment of depression in the future. But evidence suggests that the increased provision of these treatments for common mental health disorders has had little impact on prevalence and novel methods of treating and preventing these conditions are still needed (Jorm et al., 2017).

Physical activity is consistently reported as having antidepressant effects (Schuch et al., 2018). Physical activity refers to any bodily movement by the skeletal muscles that requires energy expenditure (Caspersen et al., 1985). A recent meta-analysis of 49 prospective cohort studies including 1,837,794 person-years found that people with high levels of physical activity had 17% lower odds of depression (OR = 0.83, CI = 0.79, 0.88) than people with low physical activity (Schuch et al., 2018). Other meta-analyses have also found that low physical activity is associated with a greater risk of depression (Mammen and Faulkner, 2013; Teychenne et al., 2010). Other meta-analyses found that low cardiorespiratory fitness (CRF), an indicator of physical inactivity, was associated with a 64% higher risk of depression (HR = 1.64, CI = 1.29, 2.08) than high CRF across at least 3,540,450 person-years of data (Kandola et al., 2019; Schuch et al., 2016a).

The benefits of physical activity for depression extend beyond risk reduction. Exercise refers to a subset of physical activity that is planned and structured towards improving physical fitness (Caspersen et al., 1985), such as running or weight training. Several systematic reviews have found that exercise can reduce the symptoms of depression with a moderate-to-large effect size and can be a useful addition to pharmacotherapy and psychotherapy (Bridle et al., 2012; Cooney et al., 2013; Josefsson et al., 2014; Kvam et al., 2016; Schuch et al., 2016b). In people with depression, CRF is inversely correlated with symptom severity (Papasavvas et al., 2016). Including exercise in the treatment of depression also has several additional benefits. For example, exercise can reduce the risk of cardiovascular disease (Cornelissen and Smart, 2013), which is elevated in people with depression (Correll et al., 2017).

Despite extensive research on the efficacy of exercise and physical activity, the mechanisms through which they produce antidepressant effects remain unclear. An attempt has been made to understand the psychosocial and biological mechanisms of physical activity in the mental health of young people (Lubans et al., 2016). But little has been done to summarise these mechanisms in adults and focussing on depression.

This review will provide a comprehensive summary of the key biological and psychosocial mechanisms through which physical activity produces an antidepressant effect. We conducted non-systematic literature searches to identify possible mechanisms that are influenced by physical activity and may also play a role in the pathophysiology of depression. We primarily included mechanisms based on the strength of the underlying evidence. But there is a paucity of direct, high-quality evidence in this area, particularly within the psychosocial domain. To avoid omitting potentially important but understudied mechanisms, we also considered other factors such as their conceptual plausibility or their role in other forms of depression treatment.

Much of this review will focus on exercise specifically, as clinical research typically utilises this form of activity. Structured exercise plans are an efficient method to operationalise and standardise physical activity within a clinical trial. It is also possible that other characteristics of exercise are conducive to depression treatment. For example, exercise is typically performed during leisure time, which is associated with mental health benefits, unlike other domains such as activity during work (White et al., 2017).

We will also detail how furthering our understanding of these mechanisms can help to identify other factors that moderate or confound the relationship between physical activity and depression. For simplicity, we will assume a fundamental overlap in the mechanisms through which physical activity and exercise influence mental health.