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bioRxiv · 10.64898/2025.11.30.689896

Sex-specific brain structural predictors and outcomes of adolescent depression trajectories

Ding, Q.·Rakesh, D.·Khetana, M.·Whittle, S.
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Abstract

ObjectivesDepressive symptoms often emerge and increase during adolescence, yet the neural predictors and long-term brain outcomes associated with depressive trajectories remain poorly understood. This study adopts a trajectory-based approach to explore the temporal relationship between brain structure and dynamic changes in depressive symptoms across adolescence. MethodsWe used a large longitudinal adolescent neuroimaging sample across five annual waves (n = 11,862; mean age = 9.91 at baseline) from the ABCD study. First, growth mixture models were applied separately for males and females to identify distinct developmental trajectories of depressive symptoms. We then used linear mixed-effects models to identify which baseline brain structural features differentiated trajectory classes, and how these trajectories influenced subsequent brain structure. ResultsWe identified high-decreasing, stable-low, and low-increasing trajectories in females, and relatively stable high, moderate, and low trajectories in males. No baseline brain regions were found to be associated with female trajectories, whereas smaller global brain measures (total subcortical volume, cortical volume, and surface area) predicted the high trajectory in males. Regarding brain outcomes, a low-increasing trajectory in females was associated with smaller global subcortical and cortical volumes, while high and moderate trajectories in males predicted thinner global cortices. Additional trajectory-related regional brain alterations were observed in both sexes. ConclusionsThese findings highlight distinct neurodevelopmental patterns linked to depressive symptom trajectories in males and females, underscoring the importance of a sex-specific and longitudinal approach to identifying neural risk and outcomes in adolescent depression.

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Ding, Q., Rakesh, D., Khetana, M., Whittle, S.. 2025-12-02. Sex-specific brain structural predictors and outcomes of adolescent depression trajectories. https://doi.org/10.64898/2025.11.30.689896

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