The mechanisms underlying the antidepressant effects of physical activity

Depression is very common, and has a devastating impact on people's lives. Physical activity is an effective treatment, but the mechanisms driving symptom improvement, particularly psychological and brain processes, remain unclear. Such information could help inform new treatment strategies.

We hypothesise that physical activity boosts reward processing, specifically effort-based decision-making, through reducing inflammation, increasing dopamine transmission and modulating reward-processing brain circuitry. We will test this hypothesis with a mechanistic randomised controlled trial in 250 depressed participants, undergoing eight weeks of either aerobic exercise (active intervention) or relaxation/stretching (control). To measure reward processing we will use computerised cognitive tests combined with computational modelling. We will assess changes in reward/effort-processing brain circuity using functional neuroimaging, dopamine using positron emission tomography, and acquire blood samples to assess immune-metabolic markers. We predict that exercise will initially preferentially improve depressive symptoms related to motivation and cognition, which we will test using dynamic structural equation modelling of daily smartphone measurements.

This design allows us to answer three central questions addressing causality: whether exercise changes these proposed mechanisms (modulation); the degree to which such changes are related to improvements in symptoms (mediation); and whether symptomatic improvement following the exercise intervention can be predicted from baseline measures (moderation).