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.

Gray Matter Structural Alterations in Social Anxiety Disorder: A Voxel-Based Meta-Analysis

“…It also may be that VBM analyses have insufficient sensitivity to detect variation in small limbic structures (e.g., the amygdala and hippocampus) ( 100 ). For instance, a recent mega-analysis study included in our research found no anxiety-related amygdaloid and hippocampal volume variation in SAD patients using the VBM method ( 40 ). Therefore, future research is needed to attentively survey the processes of atrophy/hypertrophy of limbic structures and further determine whether there is a specific correlation of these structures with SAD.…”

“…As shown in Figure 1 and Table 1 , we identified and included 11 studies (38–48) in the current meta-analysis, comparing the regional GMV differences between 470 SAD patients and 522 healthy subjects at the whole-brain level. In these studies, one mega-analysis ( 40 ) collected structural MRI scan data at research centers located in Europe, Africa and North-America. Table 1 presents the characteristics of all included studies.…”

Whole Brain and Cranial Size Adjustments in Volumetric Brain Analyses of Sex- and Age-Related Trends

“…Several in vivo imaging studies have attempted to quantify the age-related changes in the whole brain volume, gray matter, white matter, and the CSF compartments, using various imaging techniques (Good et al, 2001;Curiati et al, 2009;Salat et al, 2009;Farokhian et al, 2017). The contradictory results provided by MRI were linked to the discrepancies in the age ranges, analyzed regions, and assignments of the methodological background (Bas-Hoogendam et al, 2017). It may be, thus, concluded, that choosing the optimal methodology of data collection and analysis is essential to avoid an unacceptable bias.…”

Sex differences in the developing brain: insights from multimodal neuroimaging

“…However, a review of structural imaging studies across multiple anxiety disorders revealed overall mixed results, with studies showing both increased and decreased regional volumes that varied across anxiety disorders and within single anxiety diagnoses [115]. Likewise, a mega-analysis of social anxiety studies was unable to replicate previously reported brain structure abnormalities in a number of regions [116]. In contrast, cerebral blood flow shows a more consistent relationship with anxiety.…”