Neurobiological, Psychosocial, and Behavioral Mechanisms Mediating Associations Between Physical Activity and Psychiatric Symptoms in Youth in the Netherlands

María Rodriguez-Ayllon, Alexander Neumann, Amy Hofman, Trudy Voortman, David R. Lubans, Junwen Yang-Huang, Pauline W. Jansen, Hein Raat, Meike W. Vernooij*, Ryan L. Muetzel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Understanding the mechanisms by which physical activity is associated with a lower risk of psychiatric symptoms may stimulate the identification of cost-efficient strategies for preventing and treating mental illness at early life stages. 


To examine neurobiological, psychosocial, and behavioral mechanisms that mediate associations of physical activity with psychiatric symptoms in youth by testing an integrated model. 

Design, setting, and participants: 

Generation R is an ongoing prospective population-based cohort study collecting data from fetal life until young adulthood in a multiethnic urban population in the Netherlands. Pregnant women living in Rotterdam with an expected delivery date between April 2002 and January 2006 were eligible for participation along with their children born during this time. Data were collected at a single research center in the Erasmus Medical Center Sophia Children's Hospital. For the current study, data were analyzed from 4216 children with complete data on both exposure and outcome at ages 6, 10, and 13 years. Data were analyzed from January 2021 to November 2022. 


Physical activity was ascertained at age 6 years (visit 1) via parent report and included weekly frequency and duration of walking or cycling to or from school, physical education at school, outdoor play, swimming, and sports participation. 

Main Outcomes and Measures: 

Psychiatric symptoms (internalizing and externalizing symptoms) were assessed at age 6 years (visit 1) and at age 13 years (visit 3) using the Child Behavior Checklist. Several mechanisms were explored as mediators, measured at age 10 years (visit 2). Neurobiological mechanisms included total brain volume, white matter microstructure, and resting-state connectivity assessed using a 3-T magnetic resonance imaging scanner. Psychosocial mechanisms included self-esteem, body image, and friendship. Behavioral mechanisms included sleep quality, diet quality, and recreational screen time. Pearson correlations between physical activity measures and psychiatric symptoms were calculated, with false discovery rate correction applied to account for the number of tests performed. Mediation analyses were performed when a correlation (defined as false discovery rate P <.05) between exposure and outcome was observed and were adjusted for confounders. 


Among the 4216 children included in this study, the mean (SD) age was 6.0 (0.4) years at visit 1, and 2115 participants (50.2%) were girls. More sports participation was associated with fewer internalizing symptoms (β for direct effect, -0.025; SE, 0.078; P =.03) but not externalizing symptoms. Self-esteem mediated the association between sports participation and internalizing symptoms (β for indirect effect, -0.009; SE, 0.018; P =.002). No evidence was found for associations between any other neurobiological, psychosocial, or behavioral variables. No association was found between other types of physical activity and psychiatric symptoms at these ages. 

Conclusions and Relevance: 

The integrated model presented in this cohort study evaluated potential mechanisms mediating associations between physical activity and psychiatric symptoms in youth. Self-esteem mediated an association between sports participation in childhood and internalizing symptoms in adolescence; other significant mediations were not observed. Further studies might explore whether larger effects are present in certain subgroups (eg, children at high risk of developing psychiatric symptoms), different ages, or structured sport-based physical activity interventions..

Original languageEnglish
Pages (from-to)451-458
Number of pages8
JournalJAMA Psychiatry
Issue number5
Early online date29 Mar 2023
Publication statusPublished - May 2023

Bibliographical note

Funding/Support: Dr Rodriguez-Ayllon was supported by the Ramon Areces Foundation and the Alicia Koplowitz Foundation . This study was supported by the Sophia Foundation (S18-20) and Netherlands Organization for Health Research and Development ( ZonMw ). Supercomputing resources were supported by the Netherlands Organization for Scientific Research ( Exacte Wetenschappen ), and SURFsara ( Snellius Compute Cluster , ). The Generation R Study is conducted by the Erasmus University Medical Center in close collaboration with the School of Law and the Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, and the Stichting Trombosedienst en Artsenlaboratorium Rijnmond. The general design of the Generation R Study was made possible by financial support from the Erasmus University Medical Center Rotterdam , ZonMw , the Netherlands Organization for Scientific Research , and the Ministry of Health, Welfare, and Sport . Dr Lubans is supported by a National Health and Medical Research Council research fellowship (APP1154507).

Publisher Copyright:
© 2023 American Medical Association. All rights reserved.


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