Dose-Response Relationships between Physical Exercises and Mental Health during Early Adolescence: an Investigation of the Underlying Neural and Genetic Mechanisms from the ABCD Study

Adolescence is a critical developmental with increased vulnerability to mental disorders. While the positive impact of physical exercise on adult mental health is well-established, dose-response relationships and the underlying neural and genetic mechanisms in adolescents remain elusive. Leveraging data from >11,000 pre-adolescents (9-10 years, ABCD Study) we examined associations between seven different measures of exercise dosage across 15 exercises and psychopathology, and the roles of brain function and structure and psychiatric genetic risks. Five specific exercises (basketball, baseball/softball, soccer, football, and skiing) were associated with better mental health while the beneficial effects varied with exercise types, dosage measures and dimensions of psychopathology. Interestingly, more exercise does not always translate to better mental health whilst earlier initiation was consistently advantageous. Communication between attention and default-mode brain networks mediated the beneficial effect of playing football. Crucially, exercise mitigates the detrimental effects of psychiatric genetic risks on mental health. We offer a nuanced understanding of exercise effects on adolescent mental health to promote personalized exercise-based interventions in youth. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement JZ was supported by Science and Technology Innovation 2030 - Major Projects (Grant No.2021ZD0200204), Science and Technology Innovation 2030 - Brain Science and Brain-Inspired Intelligence Project (Grant No. 2021ZD0200204), Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01), ZJLab, and NSFC 61973086. JF was supported by the 111 Project (No. B18015), the key project of Shanghai Science and Technology (No. 16JC1420402), National Key R&D Program of China (No. 2018YFC1312900), and National Natural Science Foundation of China (NSFC 91630314). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data from ABCD study is available by request (See ).