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We set out to investigate the association of the <jats:italic>BDNF<\/jats:italic> rs6265\u00a0Met allele with neurostructural phenotypes in youth BD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Caucasian youth (N\u00a0=\u00a099; 13\u201320\u00a0years; n\u00a0=\u00a056 BD, n\u00a0=\u00a043 age and sex\u2010matched healthy controls) underwent 3\u2010Tesla Magnetic Resonance Imaging and genotyping for <jats:italic>BDNF<\/jats:italic> rs6265. Region of interest (ROI) analyses of the ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), and hippocampus were complemented by vertex\u2010wise analyses examining cortical thickness, surface area (SA) and volume. Multivariable models included the main effects of diagnosis and gene, and a diagnosis\u2010by\u2010genotype interaction term, controlling for age, sex, and intracranial volume.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were no significant gene main effects or diagnosis\u2010by\u2010gene interaction effects in ROI analyses. The vertex\u2010wise analysis yielded a significant gene main effect whereby Met allele carriers had greater middle temporal gyrus SA (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.001) and supramarginal gyrus volume (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.03) than Val\/Val individuals. Significant interaction effects were found on lateral occipital lobe SA (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.03), whereby the Met allele was associated with increased SA in BD only. Interaction effects were also found on postcentral gyrus SA (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.049) and supramarginal gyrus SA (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.04), with smaller SA in BD Met carriers versus healthy control Met carriers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest that <jats:italic>BDNF<\/jats:italic> rs6265 is differentially associated with regional SA in youth BD. Further investigation is warranted to evaluate whether BDNF protein levels mediate the observed effects, and to evaluate rs6265\u2010related developmental changes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.13116","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T10:54:46Z","timestamp":1626346486000},"page":"185-194","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Neurostructural correlates of <i>BDNF<\/i> rs6265 genotype in youth bipolar disorder"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4510-188X","authenticated-orcid":false,"given":"Kody G.","family":"Kennedy","sequence":"first","affiliation":[{"name":"Centre for Youth Bipolar Disorder Centre for Addiction and Mental Health  Toronto ON Canada"},{"name":"Department of Pharmacology University of Toronto  Toronto ON 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Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Freeman","sequence":"additional","affiliation":[{"name":"Psychiatric Neurogenetics Section Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clement C.","family":"Zai","sequence":"additional","affiliation":[{"name":"Psychiatric Neurogenetics Section Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health  Toronto ON Canada"},{"name":"Department of Psychiatry University of Toronto  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James L.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Psychiatric Neurogenetics Section Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health  Toronto ON Canada"},{"name":"Department of Psychiatry University of Toronto  Toronto ON 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