Bridging brain structures and adolescent depression and anxiety symptoms: A symptom-oriented approach

Anxiety and depression show substantial heterogeneity and often emerge in adolescence. However, their brain structural associations from a symptom-oriented perspective remain unclear. This study investigated the symptom structures of adolescent anxiety and depression and identified key brain regions linking brain structure to symptoms.

A total of 1568 adolescents with elevated depressive symptoms and 413 adolescents with elevated anxiety symptoms were identified from the Adolescent Brain Cognitive Development study. Participants completed symptom assessments and underwent Magnetic Resonance Imaging scanning. A total of ten symptom-only networks and symptom-brain networks were constructed to identify the central symptoms and the key brain structure associated with depression and anxiety symptoms.

In the symptom-only networks, concentration difficulties emerged as the shared central symptom, while self-hatred and irritability were the unique central symptoms for depression and anxiety, respectively. In the symptom-brain networks, left- and right-pallidum volumes exhibited the highest bridge centrality in connection with depressive symptoms, whereas left-nucleus accumbens volume showed the highest bridge centrality in connection with anxiety symptoms. Cortical structures showed sparse connections with both depressive and anxiety symptoms.

Our findings highlight the pallidum and nucleus accumbens as key brain regions linking brain structure to adolescent depressive and anxiety symptoms. These results provide insights into the neural mechanisms of depression and anxiety from a symptom-oriented perspective and may inform targeted interventions for at-risk youth.