Dissociations in cortical thickness and surface area in non-comorbid never-treated patients with social anxiety disorder

Abstract

Background: Abnormalities of functional activation and cortical volume in brain regions involved in the neurobiology of fear and anxiety have been implicated in the pathophysiology of social anxiety disorder (SAD). However, few studies have performed separate measurements of cortical thickness (CT) and cortical surface area (CSA) which reflect different neurobiological processes. Thus, we aimed to explore the cortical morphological anomaly separately in SAD using FreeSurfer.

Methods: High-resolution structural magnetic resonance images were obtained from 32 non-comorbid never-treated adult SAD patients and 32 demography-matched healthy controls. Cortical morphometry indices including CT and CSA were separately determined by FreeSurfer and compared between the two groups via whole-brain vertex-wise analysis, while partial correlation analysis using age and gender as covariates were conducted.

Findings: The patients with SAD showed decreased CT but increased CSA near-symmetrically in the bilateral prefrontal cortex (PFC) of the dorsolateral, dorsomedial, and ventromedial subdivisions, as well as the right lateral orbitofrontal cortex; increased CSA in the left superior temporal gyrus (STG) was also observed in SAD. The CSA in the left PFC was negatively correlated with the disease duration.

Interpretation: As the balloon model hypothesis suggests that the tangentially stretched cortex may cause dissociations in cortical morphometry and affect the cortical capacity for information processing, our findings of dissociated morphological alterations in the PFC and cortical expansion in the STG may reflect the morphological alterations of the functional reorganization in those regions, and highlight the important role of those structures in the pathophysiology and neurobiology of SAD.

Funding: This study was funded by the National Natural Science Foundation of China (Grant Nos. 31700964, 31800963, 81621003, and 81820108018).

Keywords: Balloon model; Cortical surface area; Cortical thickness; Magnetic resonance imaging; Prefrontal cortex; Social anxiety disorder.

Fig. 1

Brain regions with cortical thickness differences between social anxiety disorder patients and healthy controls (corrected with Monte Carlo Null-Z Simulation of P < 0.05). Warmer colors (positive values) represent increased cortical thickness, while cooler colors (negative values) represent decreased cortical thickness in social anxiety disorder patients compared to those in healthy controls. Abbreviations: SFG, superior frontal gyrus.

Fig. 2

Brain regions with cortical surface area differences between social anxiety disorder patients and healthy controls (corrected with Monte Carlo Null-Z Simulation of P < 0.05). Warmer colors (positive values) represent increased cortical surface area, while cooler colors (negative values) represent decreased surface area in social anxiety disorder patients compared to those in healthy controls. Abbreviations: lOFC, lateral orbitofrontal cortex; rMFG, rostral middle frontal gyrus; SFG, superior frontal gyrus; STG, superior temporal gyrus.

Fig. 3

Scatterplots showing negative correlations between average cortical surface area of the left superior frontal gyrus cluster and disease durations in social anxiety disorder.