Functional connectivity strength and topology differences in social phobia adolescents with and without ADHD comorbidity

Social phobia (SP) is associated with changes in functional connectivity strength and topology. However, reported changes have been heterogeneous due to small sample sizes, inconsistent methodologies, and comorbidities, such as attention-deficit/hyperactivity disorder (ADHD), which has a high comorbidity rate with SP. Furthermore, there are few studies looking at SP in an adolescent population, a critical period for the development of the social brain. This project focuses on functional connectivity strength and topological differences in social phobia patients with and without ADHD comorbidity. We examined resting-state functional MRI images from 158 subjects, including 36 SP participants without ADHD comorbidity, 60 SP participants with ADHD comorbidity, and 62 healthy controls, with an overall average age of 14.16. We used a data-driven approach to examine impaired functional connectivity in a whole-brain analysis and higher-order topological differences in functional brain networks. We identified changes in the cerebellum and default mode network in social phobia patients as a whole, with the presence of ADHD comorbidity affecting various subsystems of the default mode network. Social phobia functional connectivity networks resembled random graphs, and local connectivity patterns in the superior occipital gyrus were different due to ADHD comorbidity. These alterations may indicate impairments in self-related processing, imagery, mentalizing, and predictive processes. We then used these changes in a linear support vector machine to distinguish between each pair of groups and achieved prediction accuracy significantly above chance rates. Our study extends prior research by showing that functional connectivity changes exist at adolescence, which are affected by ADHD comorbidity. As such, these results offer a new perspective in examining neurobiological changes in SP patients.