Multidomain Childhood Bipolar Risk Clusters and Adolescent Bipolar Spectrum Emergence in the ABCD Study
Year: 2026
Type: preprint
Abstract: Bipolar disorder (BD) often emerges during adolescence with an average seven-year diagnostic delay associated with substantial burden and mortality. Determining whether BD risk factors form interpretable subgroups in childhood may inform earlier BD risk stratification and diagnosis. This study sought to identify how multidomain childhood BD risk factors cluster in a population-based cohort, and test whether clusters were prospectively associated with adolescent BD emergence. Leveraging baseline, 2-, 4-, and 6-year follow-up data from 11,868 youth in the Adolescent Brain Cognitive Development study, baseline risk features spanning clinical/prodromal, familial, neurocognitive, and environmental domains were clustered using k-prototypes. Primary outcomes were BD-I, BD-II, BD not otherwise specified, and any bipolar spectrum disorder (BSD), as derived from the KSADS-COMP. Pooled logistic discrete-time hazard models estimated BD onsets, and generalized estimating equations estimated BD prevalence over time. Complete baseline risk data from 9,193 participants yielded a stable 2-cluster solution, comprised of higher (n = 1,391) and lower (n = 7,802) risk clusters. Higher-risk membership was associated with greater BSD onset odds, (OR = 2.74, 95% CI [2.21,3.41], p< .001). By year-6, cumulative BSD risk was 19.7% in the higher-risk cluster versus 7.9% in the lower-risk cluster (RR = 2.50, 95% CI [2.06,3.03], p< .001). Higher-risk membership was also associated with greater BSD occurrence across follow-ups. In summary, multidomain childhood BD risk variables showed a stable 2-cluster profile that prospectively stratified adolescent BSD. Nearly 1 in 5 youths in the higher-risk cluster developed a BSD by mid-adolescence. This empirically derived framework provides a foundation for future BD risk stratification and external validation.
Source: Research Square
Institution: Oregon Health & Science University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Urban air pollution and neurobehavioral trajectories in the ABCD study, The role of air pollution in emotional neurodevelopment and risk for psychiatric disorders, 9/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U MICHIGAN, 20/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT VCU, 3/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U MINNESOTA, 4/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT FIU, 7/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT YALE, 17/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UCLA, 15/21 ABCD-USA Consortium: Research Project Site at LIBR, 16/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UNIVERSITY OF ROCHESTER, 8/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT CHLA, ABCD-USA Consortium: Coordinating Center, 6/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT OHSU, 10/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT SRI, 12/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U PITTSBURGH, 19/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UVM, 1/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U UTAH, 11/21 ABCD-USA Consortium: Research Project Site at UWM, ABCD-USA Consortium: Data Analysis, Informatics and Resource Center, 21/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT WUSTL, 13/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT MUSC, 5/21 ABCD-USA Consortium: Research Project Site at UC San Diego, 18/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT THE UNIVERSITY OF FLORIDA, 2/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UMB, 14/21 ABCD-USA Consortium: Research Project Site at CU Boulder
OpenAlex ID: W7164888441