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

Janna Marie Bas-Hoogendam, Henk van Steenbergen, J. Nienke Pannekoek, Jean Paul Fouche, Christine Lochner, Coenraad J. Hattingh, Henk R. Cremers, Tomas Furmark, Kristoffer N.T. Månsson, Andreas Frick, Jonas Engman, Carl Johan Boraxbekk, Per Carlbring, Gerhard Andersson, Mats Fredrikson, Thomas Straube, Jutta Peterburs, Heide Klumpp, K. Luan Phan, Karin RoelofsDick J. Veltman, Marie José van Tol, Dan J. Stein, Nic J.A. van der Wee

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)678-688
Number of pages11
JournalNeuroImage: Clinical
StatePublished - 2017


  • Gray matter
  • Mega-analysis
  • Social anxiety disorder
  • Striatum
  • Structural MRI
  • Voxel-based morphometry

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience


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