Physical activity (PA) and improvements in cardiorespiratory fitness (CRF) may protect against or alleviate depression through neuroplastic mechanisms within disrupted brain networks underlying cognitive and affective symptoms. There is a scarcity of research examining the effects of PA and CRF on structural and functional brain networks in representative samples spanning adulthood. Further, little is known about the interactions of PA and CRF with depression on these networks. To address this problem, this dissertation made use of a publicly available dataset to examine the associations among PA, CRF, and depression symptoms in a community sample of adults between the ages of 18-85. Magnetic resonance imaging measures were leveraged to determine whether structural and functional brain network features associated with PA and CRF were moderated by depression symptom severity.

The first aim examined effects of PA and CRF on depression symptoms within a measured variable path analysis. PA had a direct and beneficial effect on depression symptoms only in females, and this effect was not mediated by CRF. The second aim examined brain structural correlates of PA and CRF and tested moderation of these effects by depression symptoms. CRF was negatively associated with cortical thickness in the left superior frontal lobe, and this association was stronger as depression symptoms increased. CRF was negatively associated with amygdala and nucleus accumbens volume, while a positive association of PA with nucleus accumbens volume was observed at moderate-to-severe levels of depression symptoms. The third aim examined functional brain network correlates of PA and CRF and moderation by depression symptoms. CRF was positively associated with whole-brain modularity, between-network connectivity of the central executive and salience networks, and within-network connectivity of the default mode, central executive, and salience networks. The association of CRF and default mode network connectivity was stronger in the presence of moderate-to-severe depression symptoms. Taken together, these results suggest psychosocial effects of PA on depression symptoms and interacting effects of CRF and depression on brain structure and function. Progressing our understanding of these effects will have important implications for translating physical activity and exercise research as a therapeutic strategy for depression symptoms.