Does physical activity prevent depression or does depression prevent physical activity?

Exercise has been shown to improve mood^[1] and sleep^[2] and even boost memory and thinking^[3], perhaps through its ability to reduce insulin resistance^[4], reduce inflammation^[5], and stimulate the release of neurotrophic growth factors^[6] in the brain. In support of these neurotrophic effects^[7] of exercise, numerous studies have observed that the prefrontal cortex^[8] and medial temporal cortex (areas of the brain that control thinking and memory) are often larger in volume in people who exercise compared to those who do not exercise. Luckily for people who do not currently exercise, just six months of regular aerobic exercise performed at moderate intensity can increase the volume^[9] of select parts of the brain.

Increasing evidence^[10] points to size and structural changes in brain areas involved in mood, memory, and decision-making during depressive episodes. Initial evidence^[11] suggests that this remodeling of the brain can be prevented and potentially reversed with antidepressant and mood-stabilizing medications. Physical activity may offer similar therapeutic benefits without the side effects, as exercise has also been shown to improve the brain’s capacity to produce and absorb the neurotransmitters serotonin and dopamine^[12], both of which are believed to play a role in depressed brains. Additionally, exercise reduces activity of stress hormones and stimulates the growth of new brain cells^[13]. Exercise has also been shown to partially reverse the age-related volume loss of the hippocampus^[14], the area of the brain responsible for processing long-term memory and emotional response.

Meta-analyses^[15] of randomized controlled trials have linked physical activity to reduced depressive symptoms in people with depression, but these don’t necessarily speak to whether physical activity can prevent depression. On the other hand, prospective studies^[16] have found associations between higher levels of physical activity and reduced risk for developing depression later on, but these studies can’t establish a causal link between exercising and reducing depression risk, since depression itself^[17] can lead to less physical activity, and so may its risk factors.

To help determine whether people who exercise are at lower risk of depression or whether people at risk for depression exercise less, the study under review used genetic data in a Mendelian randomization analysis to examine the relationship between physical activity and depression.

Depression is associated with lower levels of physical activity, but it is unclear whether individuals who do not exercise are at greater risk for depression or whether individuals who are at risk for depression are at greater risk for inactivity. The study under review used a Mendelian randomization analysis to help determine the path of causality.