{"doi":"10.1101/2025.11.20.689391","title":"Developmental deviations of structural connectivity in youths with ADHD predict symptom and treatment outcomes","abstract":"Attention-deficit/hyperactivity disorder (ADHD) lacks validated biomarkers to track symptom development or guide treatment selection in youth. We quantified individual deviations from normative age-related trajectories of white-matter structural connectivity (SC) across two independent cohorts: 6,687 typically developing and 1,114 ADHD scans from the ABCD study, and 292 typically developing and 482 ADHD participants from a Chinese cohort. Youth with ADHD showed pronounced SC deviations, especially in higher-order association pathways. A subset of connections showed ADHD-specific developmental reductions in deviations beyond typical developmental patterns, and these changes mediated the age-related decline in ADHD symptoms. Longitudinal within-individual analyses demonstrated that decreases in deviation over two years tracked symptom improvement. Baseline deviations also predicted 12-week treatment response to atomoxetine, but not methylphenidate, and follow-up imaging revealed treatment-related reductions in deviation. Together, these findings identify SC deviation as a robust developmental biomarker with prognostic and theragnostic relevance for ADHD, supporting precision care through risk stratification, individualized pharmacotherapy selection, and objective monitoring of treatment effects.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":559556,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7521,"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":1460822,"name":"Zhao Fu","orcid":"0000-0003-4780-6602","position":1,"is_corresponding":false},{"id":1164917,"name":"Haoshu Xu","orcid":null,"position":2,"is_corresponding":false},{"id":1461382,"name":"Kangfuxi Zhang","orcid":null,"position":3,"is_corresponding":false},{"id":1460823,"name":"Hang Yang","orcid":"0000-0002-5524-4227","position":4,"is_corresponding":false},{"id":954360,"name":"Li Yang","orcid":"0000-0003-3771-5969","position":5,"is_corresponding":false},{"id":1158240,"name":"Yilu Zhao","orcid":"0000-0003-3219-3188","position":6,"is_corresponding":false},{"id":1460824,"name":"Xiangyu Zheng","orcid":"0009-0002-8984-7437","position":7,"is_corresponding":false},{"id":627745,"name":"Arielle S. Keller","orcid":"0000-0003-4708-1672","position":8,"is_corresponding":false},{"id":1460825,"name":"Ting Xu","orcid":"0000-0003-3086-6916","position":9,"is_corresponding":false},{"id":373438,"name":"Runsen Chen","orcid":"0000-0002-2145-8630","position":10,"is_corresponding":false},{"id":294938,"name":"Weidong Cai","orcid":"0000-0001-9581-7774","position":11,"is_corresponding":false},{"id":322955,"name":"Qingjiu Cao","orcid":"0009-0005-8825-7760","position":12,"is_corresponding":false},{"id":235284,"name":"Zaixu Cui","orcid":"0000-0003-4385-8106","position":14,"is_corresponding":false},{"id":1370903,"name":"Xiaoyu Xu","orcid":"0000-0002-8124-6445","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:55:34.849815Z","pmid":"41332541","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":[]}