Exercise and Depression – Antidepressant Effects of Physical Activity (2023 Update)

Lifestyle:

• Depression negatively impacts lifestyle choices such as an unbalanced and low-quality diet [Quirk et al. 2013], sedentary behaviour [Schuch et al. 2017],  higher rates of smoking [Luger et al. 2014] and alcohol abuse [Boden and Fergusson 2011].
• Although exercise is not known to reduce smoking or alcohol consumption, exercise can effectively reduce body weight, although not as effectively as a hypocaloric diet. [Verheggen et al. 2016]

Lifespan:

• Depression increases the incidence of cardiovascular diseases such as stroke and cardiac failure [Gathright et al. 2017], [Shi et al. 2017].
• Although this may in part be due to poor adherence to cardiovascular medications, exercise has been shown to reduce mortality rates similar to medications in individuals with coronary heart disease, stroke, heart failure, and diabetes [Naci and Ioannidis 2015].

Physical health:

• Exercise is an important component of weight management as it helps regulate appetite hormones [Schubert et al. 2014], increase metabolic rate [Marson et al. 2016], and improve sleep quality and duration [Kelley and Kelley 2017].
• Exercise lowers fasting insulin and HbA1c, and overtime is associated with reduced LDL and fasting glucose levels. [Lin et al. 2015].

Although several studies have pointed to a protective role, the Cochrane Review in 2013 suggests exercise is no more effective than psychological or pharmacological therapies, resulting in confusion and controversy. [Cooney et al. 2013] 

A subsequent analysis in JAMA concluded that the antidepressant effect of exercise “may be small” [Cooney et al. 2014], and more recently, a systematic review published in the BMJ concluded that “exercise interventions only produce small or negligible antidepressant effects“. [Krogh et al. 2017]

However, several questions have been raised about the validity of the Cochrane data. When scrutinising methodology and inclusion/exclusion criteria, it has been suggested that the strength and quality of the Cochrane review are flawed. [Ekkekakis 2014]

Although it is uncertain whether physical activity causally influences the risk for depression, it has recently been shown that when including objectively assessed measures, physical activity had a protective and causal relationship with reducing the risk of depression. [Choi et al. 2019]

A review of 97 systematic reviews examining the effectiveness of physical activity in populations including healthy adults, people with mental health disorders, and various chronic diseases showed that: [Singh et al., 2023]

• Physical activity had medium effects on depression, anxiety and psychological distress.
• The most significant benefits were seen in people with depression, HIV and kidney disease, pregnant and postpartum women, and healthy individuals.
• Higher-intensity physical activity was associated with more significant improvements in symptoms.
• The effectiveness of physical activity interventions diminished with longer-duration interventions.

The question for future studies is whether interventions that increase physical activity can reduce the incidence of depression.

Low physical activity is associated with a greater risk of depression and some researchers also suggest that exercise can reduce the symptoms of depression although the exact mechanisms through which they produce this effect is unknown. [Kandola et al. 2019]

Some postulated mechanisms are as follows:

Neuroplasticity

• Reduced hippocampal neuroplasticity is increasingly considered to be a central driver of the pathogenesis of depression as well as remission and recurrence. [Alves et al 2017]
• Abnormal cerebral blood flow is commonly observed in depressed patients, which is hypothesized to impair several neuroplastic mechanisms. [Gurjal et al. 2017]
• Exercise stimulates a cascade of several neurotrophic factors that induce neuroplasticity. [Stimpson et al. 2016]
• Exercise influences brain morphology primarily through adaptive improvements in cerebral blood flow. [Maass et al. 2015]

Inflammation

• Chronic low-grade inflammation is suggested to be a risk factor for the development of depression through dysregulation of BDNF and kynurenine pathways.
• Pro-inflammatory markers such as IL-6, TNF-alpha, and C-reactive protein are routinely found to be elevated in patients with depression. [Kohler et al. 2017]
• Exercise can reduce the circulating levels of several inflammatory markers through the release of muscle-derived myokines. [Brown et al. 2015]
• There is a homeostatic adjustment to lower levels of inflammation with repeated bouts of exercise, which can create a long-lasting anti-inflammatory environment.

Oxidative stress

• Patients with depression have been shown to have greater levels of DNA and lipid damage caused by excess reactive oxygen species (ROS) and reactive nitrogen species (RNS).
• Oxidative stress degrades antioxidant defences and stimulates the production of pro-inflammatory cytokines, which over time can affect neuroplasticity.
• Regular bouts of exercise are associated with an adaptive response to the production of ROS that improves oxidative stress resilience.
• Long-term exercise was also linked to resilience to oxidative stress regardless of intensity, volume, or type of exercise. [de Sousa et al 2017]

Neuroendocrine system

• Dysregulation of the HPA axis is proposed to be a key mediator of the association between physiological stress and depression.  [Chrousos 2009]
• Persistent increases in glucocorticoids such as cortisol exert neurotoxic effects on the prefrontal cortex and hippocampus
• Regular exercise produces an adaptive and protective response to stress that effectively blunts the cortisol response. [Hotting et al 2016]
• Preliminary research shows that exercise can reduce cortisol reactivity, which exerted a reduction in depressive symptoms.  [Foley et al 2008]

Psychosocial dysfunction in domains such as perception, identification, and interpretation of social cues is commonly observed in depressed patients.

These impairments can often exacerbate depressive symptoms through incorrect or biased assessment of social interactions, which further promote social avoidance and enhance feelings of isolation. [Weightman et al. 2014]

Self-esteem:

• Self-esteem and physical self-perception of image can influence and exacerbate depression.
• Exercise can improve body image and promote physical self-perception, possibly through an increase in muscle mass and reductions in body fat [Annesi and Porter 2015].

Social support:

• Social relationships that feel sufficiently supportive can be protective against depression as well as preventing the worsening of depressive symptoms in patients. [Ozbay et al. 2007]
• Team sports, for instance, can provide ample interaction and socialisation opportunities that improve social support networks and reduce the risk of depression.

Self-efficacy: 

• Self-inefficacy can worsen depressive symptoms if goals are not achieved, creating an aversive cycle that prevents a person from pursuing future goals or tasks.
• Exercise can increase the belief that a person has a situation-specific self-confidence by improving physical abilities as well as through learning new skills. [White et al. 2009]

Physical exercise is included as part of the guidelines in the management of depression.

Clinicians should incorporate the evaluation of physical activity in their clinical history. The Ask, Assess and Advise (3As) approach can be a simple yet effective strategy in prescribing physical activity. [Visit the Public Health Scotland Website for more details]

Evidence shows the following health benefits could be achieved from 10 minutes of brisk walking (at least 4.83 km/h) per day for 7 days: [Public Health England]

• Increased physical fitness
• Greater ease of performance of everyday physical activities
• Improved mood
• Improved quality of life
• Increased body leanness and healthier weight
• 15% reduction in risk of early death

The WHO physical activity guidelines recommend at least 150 mins/week of moderate-intensity physical activity or equivalent. This equates to 5 kJ/kg/day; 10kj/kg/day corresponds to the WHO recommendations of 300 minutes per week of moderate-intensity physical activity for additional health benefits.

A MET is a ratio of a person’s working metabolic rate relative to their resting metabolic rate. Metabolic rate is the rate of energy expended per unit of time.

1 MET = no energy used or sitting still

4.5 METs = 4 times the energy expenditure compared to sitting still.

The diagram below shows the physical activity energy expenditure (PAEE) of common activities performed during leisure time and at work.

Increasing PAEE by 1 kJ/kg/day per year (equivalent to a trajectory of being inactive at baseline and then subsequently increasing physical activity to 5 and 10 kJ/kg/day), five and 10 years later, respectively—was associated with a 24% lower risk of all-cause mortality. [Mok et al., 2019]

This gain in longevity from increasing physical activity over time is in addition to the benefits already accrued from baseline physical activity, such as a 30% lower risk of mortality for a between-individual difference of 10 kJ/kg/day.

A collaborative approach is preferred with mental health experts working closely with personal trainers, clinical exercise physiologists, wellness specialists, and physical therapists if possible.

While exercise and physical activity is a useful strategy in the treatment of depression, the optimal exercise prescription (“dose” of exercise – intensity, frequency, session duration), and the response remains unknown.

Despite the lack of clear guidance at this point in time, clinicians should recommend physical activity to patients as part of a holistic treatment strategy in depression.

Learn More:

Exercise in psychosis