{"doi":"10.1111/jcpp.70053","title":"Psychostimulant treatment uniquely reduces left uncinate fasciculus microstructural integrity in <scp>ADHD</scp> youth with a familial risk for bipolar I disorder: a 12‐week <scp>DTI</scp> study","abstract":"BACKGROUND: Bipolar I disorder (BD) is associated with reduced white matter microstructural integrity in the uncinate fasciculus (UF), a primary fiber tract connecting frontolimbic systems. Although familial history for BD, attention-deficit/hyperactivity disorder (ADHD), and psychostimulants are important risk factors implicated in BD pathoetiology, their impact on UF microstructure remains poorly understood. METHODS: This diffusion tensor imaging study investigated UF microstructural integrity prior to and following 12 weeks of psychostimulant treatment in ADHD youth with ('high-risk', HR) and without ('low-risk', LR) a first-degree relative with BD. Healthy controls were included for comparative purposes. LR youth received 12-week open-label mixed amphetamine salts-extended release (MAS-XR), and HR youth were randomized to either MAS-XR or placebo (PLA). Bilateral UF fractional anisotropy (FA) and axial diffusivity (AD) were assessed using automated fiber quantification. RESULTS: 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-week MAS-XR treatment, significant group-by-time interactions were found for left UF FA and AD between HR-MAS and LR-MAS, as well as for left UF FA between HR-MAS and HR-PLA. Specifically, left UF FA and UF AD decreased significantly in HR-MAS but remained unchanged in LR-MAS and HR-PLA groups. At week 12, left UF FA was lower in HR-MAS relative to HC but not in LR-MAS or HR-PLA. Segment-wise analyses further revealed that UF microstructural changes in the HR-MAS group were localized to the anterior segments. CONCLUSIONS: These results suggest that HR-ADHD youth are uniquely vulnerable to reductions in left UF microstructural integrity following psychostimulant treatment, suggesting potential relevance to BD pathoprogression.","journal":"Journal of Child Psychology and Psychiatry","year":2025,"id":575122,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1483110,"name":"Wen Chen","orcid":"0000-0001-8493-0157","position":1,"is_corresponding":false},{"id":680687,"name":"Du Lei","orcid":"0000-0002-3503-3692","position":2,"is_corresponding":false},{"id":1483111,"name":"Ziyu Zhu","orcid":"0009-0005-0268-9563","position":3,"is_corresponding":false},{"id":505035,"name":"Maxwell J. Tallman","orcid":"0000-0003-3036-561X","position":4,"is_corresponding":false},{"id":668109,"name":"Nanfang Pan","orcid":"0000-0002-5651-556X","position":5,"is_corresponding":false},{"id":1218552,"name":"Lisha Zhang","orcid":"0000-0003-2082-5125","position":6,"is_corresponding":false},{"id":427358,"name":"L. Rodrigo Patino","orcid":null,"position":7,"is_corresponding":false},{"id":344413,"name":"John A. Sweeney","orcid":"0000-0003-1752-2828","position":8,"is_corresponding":false},{"id":300727,"name":"Melissa P. DelBello","orcid":"0000-0003-1837-4126","position":9,"is_corresponding":false},{"id":426301,"name":"Robert K. McNamara","orcid":"0000-0002-9703-8114","position":10,"is_corresponding":false},{"id":680690,"name":"Kun Qin","orcid":"0000-0003-1254-6388","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:57:48.486077Z","pmid":"40960004","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}