Future studies should also examine personalized exercise augmentation strategies to both pharmacological and psychological treatments for MDD and bipolar disorder, or strategies based on specific moderators and mediators of outcomes. It is likely that different individuals will benefit greater from (or will be more likely to adhere to) specific types and duration of exercise and thus, developing treatment algorithms based one’s demographic and clinical features would maximize treatment efficacy. Further research is also warranted to elucidate the specific mechanisms of action by which exercise improves mood. We highlight a few key pathways (BDNF, oxidative stress, and epigenetics) that have been peripherally demonstrated in clinical trials, but it is likely that multiple interacting pathways are responsible for the antidepressant effects of exercise. With a deeper understanding of these pathways, we can create more effective, and targeted, interventions as well as begin to identify individuals for whom exercise may be the most appropriate or helpful by investigating moderators of exercise.
