Gray Matter Abnormalities in Social Anxiety Disorder: Primary, Replication, and Specificity Studies

Background: Despite increasing evidence that neuroanatomical abnormalities underlie pathological anxiety, social anxiety disorder (SAD)-although among the most common of anxiety disorders-has received little attention. With magnetic resonance imaging, we: 1) examined gray matter (GM) differences between generalized SAD and healthy control groups; 2) retested the findings in an independent clinical sample; and 3) tested for specificity by contrasting the SAD group to a separate group of panic disorder (PD) subjects. Methods: The primary SAD group (n = 16) was required to meet DSM-IV criteria for SAD, with onset by age 30 years; control subjects (n = 20) had no lifetime history of anxiety. The replication sample included 17 generalized SAD and 17 control subjects. The PD comparison group (n = 16) was required to have no lifetime SAD. Images were acquired on a 1.5-Tesla GE Signa magnetic resonance imaging scanner with a three-dimensional T1-weighted spoiled gradient recalled pulse sequence. Morphological differences were determined with voxel-based morphometry, in SPM8. Results: After adjusting for age, gender, and total intracranial volume, SAD (as compared with control) subjects had greater GM in the left parahippocampal and middle occipital, and bilateral supramarginal and angular cortices, and left cerebellum; and lower GM in bilateral temporal poles and left lateral orbitofrontal cortex. Cerebellar, parahippocampal, and temporal pole differences were observed in both samples, survived whole brain corrections, and were not observed in the PD group, pointing to relative specificity to SAD. Conclusions: These findings parallel the functional literature on SAD and suggest structural abnormalities underlying the functional disturbances.