Introduction: Prodromal symptoms of mania in children are predictive of the later development of bipolar disorder; yet, the neurostructural correlates of these early symptoms remain poorly understood. This study aimed to investigate the association between prodromal mania symptoms and brain structure in a large cohort of children.
Methods: We analyzed data from 10,662 nine- to 10-year-old children from the Adolescent Brain Cognitive Development (ABCD) Study, employing structural equation modeling to examine the concurrent and longitudinal associations between prodromal mania symptoms and cortical and subcortical gray matter volume.
Results: After adjusting for multiple comparisons and controlling for age, sex, scanner model, socioeconomic status, and medication use, we found that baseline mania symptoms were associated with reduced gray matter volume across both cortical and subcortical areas, suggesting a global effect. These findings were further supported by the loss of these effects when total intracranial volume was included as an additional covariate, suggesting that smaller overall brain size, rather than specific regional effects, is related to prodromal mania symptoms. Lastly, longitudinal analyses revealed that brain volume at baseline did not predict prodromal mania symptoms at the second-year follow-up.
Conclusion: Our results support the structural differences observed in adults with bipolar disorder in prior work and refine our understanding of the neurostructural correlates of prodromal mania symptoms in children. These findings could enhance early identification and intervention efforts for youth at risk of developing bipolar disorder.
Keywords: brain structure; children; gray matter volume; mania; pathophysiology.
© 2025 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.