Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder

Abstract

Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric co-morbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in gray matter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multi-site imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples. An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n = 174) and healthy control (HC)-participants (n = 213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis 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. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.

Keywords: Gray matter; Mega-analysis; Social anxiety disorder; Striatum; Structural MRI; Voxel-based morphometry.

Graphical abstract

Fig. 1

(A) Larger GM volume in social anxiety disorder (SAD)-patients (n = 174) relative to healthy control (HC)-participants (n = 213) in the right dorsal striatum (p < 0.05, small-volume corrected). (B) Dot density plot illustrating the group difference in GM volume in the dorsal striatum. (C) Scatterplot illustrating the relationship between social anxiety symptoms in a subset of SAD-patients (n = 148; measured with the Liebowitz Social Anxiety Scale, LSAS) and GM volume in the dorsal striatum (Spearman's rho = 0.21, p < 0.05).

Fig. 2

Illustration of relation between effect size and power to detect effect, given the current sample size (n = 174 SAD-patients and n = 213 HC-participants), calculated using https://www.ai-therapy.com/psychology-statistics/power-calculator.