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The aims of the study were to examine whether levels of plasma\u2010derived neurotrophic factors were associated with brain health indicators in children with overweight or obesity; and to test whether these associations were moderated by cardiorespiratory fitness. 100 children (41% girls) were included in this analysis. Plasma levels of brain\u2010derived neurotrophic factor, insulin\u2010like growth factor\u20101, vascular endothelial growth factor A, and epidermal growth factor were determined by XMap technology. Academic performance and executive function were assessed using validated neuropsychological tests. Hippocampal volume was measured using magnetic resonance imaging. Cardiorespiratory fitness was assessed using the 20\u2010m Shuttle Run Test. Insulin\u2010like growth factor\u20101 was positively associated with cognitive flexibility. Stratified analyses by fitness categories (i.e. unfit vs. fit) showed that brain\u2010derived neurotrophic factor was positively associated with right posterior hippocampal volume in fit children, and epidermal growth factor was negatively associated with right hippocampal, and right anterior hippocampal volumes in their unfit peers, with a moderating role of cardiorespiratory fitness in these associations. However, all these significant associations disappeared after correction for multiple comparisons. The association between neurotrophic factors and brain health indicators in children with overweight\/obesity was neither strong nor consistent. These results could help enhance our understanding of determinants of brain health in children with overweight\/obesity.<\/jats:p><jats:p><jats:bold>Highlights<\/jats:bold><\/jats:p><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>This study provides novel findings on the associations between neurotrophic factors and a wide range of brain health indicators in children.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study additionally explored the role of cardiorespiratory fitness in these associations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The association between neurotrophic factors and brain health in children with overweight\/obesity was neither strong nor consistent.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Cardiorespiratory fitness moderated the associations of brain\u2010derived neurotrophic factor and epidermal growth factor with right hippocampal volume.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1080\/17461391.2022.2044912","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T15:49:15Z","timestamp":1645199355000},"page":"637-648","update-policy":"https:\/\/doi.org\/10.1080\/tandf_crossmark_01","source":"Crossref","is-referenced-by-count":9,"title":["Neurotrophic factors and brain health in children with overweight and obesity: The role of cardiorespiratory fitness"],"prefix":"10.1002","volume":"23","clinical-trial-number":[{"clinical-trial-number":"nct02295072","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6124-8876","authenticated-orcid":false,"given":"Mireia","family":"Adelantado\u2010Renau","sequence":"first","affiliation":[{"name":"LIFE Research Group University Jaume I Castell\u00f3 de la Plana Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0027-1770","authenticated-orcid":false,"given":"Irene","family":"Esteban\u2010Cornejo","sequence":"additional","affiliation":[{"name":"PROFITH \u201cPROmoting FITness and Health Through Physical Activity\u201d Research Group Sport and Health University Research Institute (iMUDS) Department of Physical and Sports Education Faculty of Sport Sciences University of Granada Granada Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2346-8776","authenticated-orcid":false,"given":"Jose","family":"Mora\u2010Gonzalez","sequence":"additional","affiliation":[{"name":"PROFITH \u201cPROmoting FITness and Health Through Physical Activity\u201d Research Group Sport and Health University Research Institute (iMUDS) Department of Physical and Sports Education Faculty of Sport Sciences University of Granada Granada Spain"},{"name":"College of Health and Human Services University of North Carolina at Charlotte Charlotte NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5374-3129","authenticated-orcid":false,"given":"Abel","family":"Plaza\u2010Florido","sequence":"additional","affiliation":[{"name":"PROFITH \u201cPROmoting FITness and Health Through Physical Activity\u201d Research Group Sport and Health University Research Institute (iMUDS) Department of Physical and Sports Education Faculty of Sport Sciences University of Granada Granada Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8267-0440","authenticated-orcid":false,"given":"Mar\u00eda","family":"Rodriguez\u2010Ayllon","sequence":"additional","affiliation":[{"name":"PROFITH \u201cPROmoting FITness and Health Through Physical Activity\u201d Research Group Sport and Health University Research Institute (iMUDS) Department of Physical and Sports Education Faculty of Sport Sciences University of Granada Granada Spain"},{"name":"Department of Epidemiology Erasmus MC University Medical Center Rotterdam Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Maldonado","sequence":"additional","affiliation":[{"name":"Department of Pediatrics School of Medicine University of Granada Granada Spain"},{"name":"Pediatric Clinical Management Unit \u201cVirgen de las Nieves\u201d University Hospital Granada Spain"},{"name":"The Institute of Biomedicine Research (Instituto de Investigaci\u00f3n Biosanitaria, ibs) Granada Spain"},{"name":"Maternal and Child Health Network (REDSAMID) Carlos III Health Institute Sevilla Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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