Differential effects of generalized anxiety and separation anxiety on brain structural development during adolescence

Excessive anxiety is highly prevalent during childhood and adolescence, with detrimental effects on somatic and mental health, and quality of life. Although structural abnormalities in the brain have been found in people with anxiety disorders, whether anxiety affects the brain development of children and adolescents remains unknown. Here, we applied a multivariate approach to two single-site MRI datasets consisting of 733 and 775 participants aged 5-18 years. Using linear support vector regression and cross-validation, brain age is estimated by predicting the chronological age from the features that combine cortical thickness and surface area of 68 brain regions. We found that gray matter can predict the chronological age of children and adolescents with a low mean absolute error. Compared to specific brain network, the whole structural brain measures predicted brain age better. Importantly, adolescents with higher generalized anxiety and those with lower separation anxiety showed lower brain age, indicating a slow development of brain structures. The relationship between anxiety and brain age of youths could also be found in parent-reported separation anxiety. The findings highlight differential effects of different anxiety types on brain structural development and suggest that different types of anxiety during childhood and adolescence should be treated differently.