Bridging Anxiety and Depression: A Network Approach in Anxious Adolescents: Anxiety-Depression Network

Background: The phenomenology and neurobiology of depressive symptoms in anxious youth is poorly understood. Methods: Association networks of anxiety and depressive symptoms were developed in adolescents with generalized anxiety disorder (GAD; N=52, mean age: 15.4±1.6 years) who had not yet developed major depressive disorder. Community analyses were used to create consensus clusters of depressive and anxiety symptoms and to identify “bridge” symptoms between the clusters. In a subset of this sample (n=39), correlations between cortical thickness and depressive symptom severity was examined. Results: Ten symptoms clustered into an anxious community, 5 clustered into a depressive community and 5 bridged the two communities: impaired schoolwork, excessive weeping, low self-esteem, disturbed appetite, and physical symptoms of depression. Patients with more depressive cluster burden had altered cortical thickness in prefrontal, inferior and medial parietal (e.g., precuneus, supramarginal) regions and had decreases in cortical thickness-age relationships in prefrontal, temporal and parietal cortices. Limitations: Data are cross-sectional and observational. Limited sample size precluded secondary analysis of comorbidities and demographics. Conclusions: In youth with GAD, a sub-set of symptoms not directly related to anxiety bridge anxiety and depression. Youth with greater depressive cluster burden had altered cortical thickness in cortical structures within the default mode and central executive networks. These alternations in cortical thickness may represent a distinct neurostructural fingerprint in anxious youth with early depressive symptoms. Finally, youth with GAD and high depressive symptoms had reduced age-cortical thickness correlations. The emergence of depressive symptoms in early GAD and cortical development may have bidirectional, neurobiological relationships.