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Although familial history for BD, attention\u2010deficit\/hyperactivity disorder (ADHD), and psychostimulants are important risk factors implicated in BD pathoetiology, their impact on UF microstructure remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This diffusion tensor imaging study investigated UF microstructural integrity prior to and following 12\u2009weeks of psychostimulant treatment in ADHD youth with (\u2018high\u2010risk\u2019, HR) and without (\u2018low\u2010risk\u2019, LR) a first\u2010degree relative with BD. Healthy controls were included for comparative purposes. LR youth received 12\u2010week open\u2010label mixed amphetamine salts\u2010extended release (MAS\u2010XR), and HR youth were randomized to either MAS\u2010XR or placebo (PLA). Bilateral UF fractional anisotropy (FA) and axial diffusivity (AD) were assessed using automated fiber quantification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 137 participants were included in the analyses. At baseline, there were no significant group differences in bilateral UF microstructural metrics. Following 12\u2010week MAS\u2010XR treatment, significant group\u2010by\u2010time interactions were found for left UF FA and AD between HR\u2010MAS and LR\u2010MAS, as well as for left UF FA between HR\u2010MAS and HR\u2010PLA. Specifically, left UF FA and UF AD decreased significantly in HR\u2010MAS but remained unchanged in LR\u2010MAS and HR\u2010PLA groups. At week 12, left UF FA was lower in HR\u2010MAS relative to HC but not in LR\u2010MAS or HR\u2010PLA. Segment\u2010wise analyses further revealed that UF microstructural changes in the HR\u2010MAS group were localized to the anterior segments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results suggest that HR\u2010ADHD youth are uniquely vulnerable to reductions in left UF microstructural integrity following psychostimulant treatment, suggesting potential relevance to BD\u00a0pathoprogression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jcpp.70053","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T09:46:56Z","timestamp":1758102416000},"page":"696-706","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Psychostimulant treatment uniquely reduces left uncinate fasciculus microstructural integrity in\n                    <scp>ADHD<\/scp>\n                    youth with a familial risk for bipolar I disorder: a 12\u2010week\n                    <scp>DTI<\/scp>\n                    study"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1254-6388","authenticated-orcid":false,"given":"Kun","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Radiology Taihe Hospital, Hubei University of Medicine  Shiyan China"},{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati OH USA"},{"name":"Mental Health Center Taihe Hospital, Hubei University of Medicine  Shiyan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology Taihe Hospital, Hubei University of Medicine  Shiyan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Du","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati OH USA"},{"name":"School of Medical Informatics Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati OH USA"},{"name":"Huaxi MR Research Center (HMRRC), Department of Radiology, The Center for Medical Imaging West China Hospital of Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxwell J.","family":"Tallman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati OH 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