Globally, depression is a leading cause of disability and has been for decades. Antidepressant medications have suboptimal outcomes and are too often associated with side effects, highlighting the need for alternative treatment options.
Although primarily known for its strong physical health benefits, exercise is increasingly recognized for its antidepressant and mental health benefits . Empirical evidence indicates that exercise is effective in treating people with depression; However, the mechanisms by which exercise exerts antidepressant effects are not fully understood.
Acute bouts of exercise have been shown to transiently modulate circulating levels of serotonin and norepinephrine, brain-derived neurotrophic factor, and a variety of immunoinflammatory mechanisms in clinical cohorts with depression. However, exercise training has not been shown to consistently modulate such mechanisms, and evidence linking these putative mechanisms and reductions in depression is lacking.
The complexity of the biological underpinnings of depression along with the intricate molecular cascade induced by exercise are significant obstacles in the attempt to unravel the effects of exercise on depression.
Despite our limited understanding of these effects, clinical evidence uniformly advocates the use of exercise to treat depression. Unfortunately, exercise remains underutilized despite being an accessible and low-cost alternative/ complementary intervention that can simultaneously reduce depression and improve overall health.
To address gaps in our understanding of the clinical and molecular effects of exercise on depression, we propose a model that leverages systems biology and multidisciplinary team science with a large-scale public health investment. Until science matches the scale of complexity and burden posed by depression, our ability to advance knowledge and treatment will continue to be plagued by fragmented, irreproducible mechanistic findings and no guidelines for standards of care.
