Brain Struct Funct. 2025 Jun 5;230(6):85. doi: 10.1007/s00429-025-02952-2.

ABSTRACT

Cardiorespiratory fitness 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 cardiorespiratory fitness on functional brain networks in representative samples spanning adulthood. Further, little is known about the interaction of cardiorespiratory fitness with depression in these networks. To address this problem, this study made use of the NKI-Rockland sample dataset and magnetic resonance imaging to examine whether functional brain network features associated with cardiorespiratory fitness were moderated by depression symptom severity in a community sample of 217 participants (134 females, 83 males) between the ages of 18 and 71 (M = 43.8 years, SD = 16.2). Cardiorespiratory fitness 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 cardiorespiratory fitness and default mode network connectivity was stronger in the presence of moderate-to-severe depression symptoms. Taken together, these observations lend support to prior work that has demonstrated the associations of cardiorespiratory fitness with reduced concurrent and prospective depression risk and symptom severity. Depression symptoms moderated default mode network connectivity, suggesting that cardiorespiratory fitness may differentially impact neural substrates for those with moderate-to-severe depression symptoms.

PMID:40471349 | DOI:10.1007/s00429-025-02952-2