Genetic influence and neural pathways underlying the dose-response relationships between wearable-measured physical activity and mental health in adolescence.

Adolescence is a critical period marked by significant physical and neurocognitive development as well as increased vulnerability to mental health issues. While the benefits of physical activity (PA) on adult mental health (MH) are well-established, the dose-response relationships and underlying neurobiological mechanisms in adolescents remain elusive. This study investigated the dose-response relationships between wearable-measured PA and MH outcomes in over 7000 adolescents (11-12 years) from the ABCD study through linear and nonlinear modeling. We further examined the genetic influence and mediation effects of brain structure and function underlying the relationships. We found that all intensity levels of PA were associated with reduced internalizing and thought problems but not with externalizing problems. Durations of moderate activity around 90 min and vigorous activity around 120 min each day and frequency of physical exercise four days each week were associated with lowest MH burden. Polygenic risk scores (PRSs) for neuropsychiatric disorders were associated with reduced step count and light activity, while PRS for walking was associated with reduced thought problems. Reduced functional connectivity between cingulo-parietal and auditory networks, and between cingulo-opercular network and left putamen is the common neural pathways mediating the associations between different PA measurements and better mental health. These findings suggest that excessive moderate and vigorous activity may not be always better for adolescent mental health. Brain functional integration and segregation centered on cognitive control as well as genetic interplay may be the potential neurobiological factors underlying the link between PA and MH.