Background: Social Anxiety Disorder (SAD) is a disabling psychiatric disorder, associated with high co-morbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning changes in gray matter (GM) in various brain regions, as well as on the relationship between GM and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multi-site imaging offers new possibilities to investigate SAD-related GM changes in larger samples.

Methods: An international multi-center mega-analysis on the largest database of SAD brain scans to date was performed to compare GM volumes of SAD-patients (n=174) and healthy participants (n=213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, amygdala-hippocampal complex, prefrontal cortex and parietal cortex.

Results: SAD-patients had larger GM volume in the dorsal striatum when compared to healthy participants. This increase correlated positively with the level of social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs.

Conclusions: The results suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Thereby, our findings indicate that sample size matters and stress the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium and its working groups. Actually, the collaborative effort for this work has resulted in the start of the ENIGMA-Anxiety workgroup.