Multi-Level Characterization of Exercise Effects on Depression: Effects on Depressive Symptoms, Cognitive Function, and Brain Health

Exercise has been established an effective treatment for depression, both as an independent treatment and as an augmentation to standard first-line treatments (e.g., medication, psychotherapy). Further, the benefits of exercise for depression have been demonstrated across age groups (i.e., older and younger adults) and in those with clinical and subclinical levels of depressive symptoms. However, the neural mechanisms underlying the antidepressant effects of exercise have only been examined in two studies with significant limitations. To address this critical gap in the literature, this dissertation leveraged data from two randomized pilot intervention studies to characterize the effects of exercise on depression across clinical, cognitive, and brain-based outcomes. To optimally translate exercise treatments to real-world settings, its efficacy in various depressed subgroups was explored, including younger (20-39 years) and older adults (60-79 years) with Major Depression, and older adults with subclinical depressive symptoms and mild cognitive impairment (MCI). Briefly, in study 1, exercise as an augmentation to medication treatment for Major Depression resulted in more rapid and stable decline in depressive symptoms, improvement in cognitive performance in younger but not older adults, and increased hippocampal-default mode network connectivity relative to medication treatment alone. Further, in regions showing reductions in cortical thickness with greater depression severity, intervention-related improvement in aerobic fitness was marginally associated with an increase in regional cortical thickness. In study 2, exercise as an augmentation to psychotherapy for older adults with subclinical depression and MCI was not effective due to suboptimal implementation of the intervention. However, results revealed greater engagement in moderate-to-vigorous physical activity and greater stability of rest-activity patterns prior to the intervention was predictive of greater improvement in cognitive performance and resulted in greater reduction in depressive symptoms over the course of the intervention, respectively. Overarching conclusions from these pilot studies highlight the utility of exercise-based interventions for alleviating clinical and subclinical levels of depression and cognitive decline, possibly via protective effects on neural pathways sensitive to the deleterious effects of depression and cognitive impairment