Neuroanatomical signatures of depression and anxiety in at-risk adolescents: A symptom-oriented perspective

Ding, Q.; Rakesh, D.; Peng, S.; Li, X.; Whittle, S.

doi:10.1101/2025.11.23.689891

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bioRxiv · 10.1101/2025.11.23.689891

Neuroanatomical signatures of depression and anxiety in at-risk adolescents: A symptom-oriented perspective

Ding, Q.·Rakesh, D.·Peng, S.·Li, X.·Whittle, S.

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Abstract

BackgroundMajor depressive disorder (MDD) and generalized anxiety disorder (GAD) often emerge in adolescence. Identifying their symptom structures and neural biomarkers in youth with elevated risk is critical for early detection and developing interventions. This study investigated the central symptoms of MDD and GAD and identified the key brain regions ("brain bridges") linking structural neuroanatomy to symptoms in at-risk adolescents. MethodsA total of 1,568 adolescents at high risk for MDD and 413 adolescents at high risk for GAD were identified from the Adolescent Brain Cognitive Development (ABCD) study. Participants completed MDD and GAD symptom assessments and underwent Magnetic Resonance Imaging scanning. We constructed 10 psychological network models incorporating symptoms and brain structural indices to identify central symptoms and brain bridges. ResultsConcentration difficulties emerged as the shared core symptom, while self-hatred and irritability were the unique central symptoms for MDD and GAD, respectively. Left- and right-pallidum volumes exhibited the highest bridge centrality for MDD symptoms, whereas left-nucleus accumbens volume showed the highest bridge centrality for GAD symptoms. ConclusionOur findings highlight the pallidum and nucleus accumbens as key brain regions linking structural anatomy to symptom networks in high-risk youth. These results provide novel insights into early neurobiological markers of MDD and GAD from a symptom-oriented perspective and may inform targeted interventions.

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Ding, Q., Rakesh, D., Peng, S., Li, X., Whittle, S.. 2025-11-25. Neuroanatomical signatures of depression and anxiety in at-risk adolescents: A symptom-oriented perspective. https://doi.org/10.1101/2025.11.23.689891

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