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

Abstract

The current insight into the neurobiological pathogenesis underlying social anxiety disorder (SAD) is still rather limited. We implemented a meta-analysis to explore the neuroanatomical basis of SAD. We undertook a systematic search of studies comparing gray matter volume (GMV) differences between SAD patients and healthy controls (HC) using a whole-brain voxel-based morphometry (VBM) approach. The anisotropic effect size version of seed-based d mapping (AES-SDM) meta-analysis was conducted to explore the GMV differences of SAD patients compared with HC. We included eleven studies with 470 SAD patients and 522 HC in the current meta-analysis. In the main meta-analysis, relative to HC, SAD patients showed larger GMVs in the left precuneus, right middle occipital gyrus (MOG) and supplementary motor area (SMA), as well as smaller GMV in the left putamen. In the subgroup analyses, compared with controls, adult patients (age ≥ 18 years) with SAD exhibited larger GMVs in the left precuneus, right superior frontal gyrus (SFG), angular gyrus, middle temporal gyrus (MTG), MOG and SMA, as well as a smaller GMV in the left thalamus; SAD patients without comorbid depressive disorder exhibited larger GMVs in the left superior parietal gyrus and precuneus, right inferior temporal gyrus, fusiform gyrus, MTG and superior temporal gyrus (STG), as well as a smaller GMV in the bilateral thalami; and currently drug-free patients with SAD exhibited a smaller GMV in the left thalamus compared with HC while no larger GMVs were found. For SAD patients with different clinical features, our study revealed directionally consistent larger cortical GMVs and smaller subcortical GMVs, including locationally consistent larger precuneus and thalamic deficits in the left brain. Age, comorbid depressive disorder and concomitant medication use of the patients might be potential confounders of SAD at the neuroanatomical level.

Individual differences in social reward and threat expectancies linked to grey matter volumes in key regions of the social brain

“…113,133 Social anxiety can be regarded as a position along a continuum ranging from a lack of anxiety, to mild shyness and then social anxiety disorder (SAD), 134,135 so our findings can meaningfully be compared with studies of SAD, which show reduced vmPFC volume. 62,136 The correlation of vmPFC rGMV with lower STE and greater SRE concurs with the well-established role of vmPFC in emotion regulation. A large-scale neuroimaging meta-analysis of affect regulation across 3 distinct domains (fear extinction, placebo effects, cognitive reappraisal) identified vmPFC activation as the only 'common neural regulator' dampening current and anticipated negative affect 66 (see also 137 ).…”

“…Recent structural magnetic resonance imaging (sMRI) studies indicate that a number of social traits are reflected in brain macrostructure (regional grey matter volume, rGMV) as assessed by voxel-based morphometry (VBM). 62 Here, we utilized VBM and an unbiased, whole brain analysis, to investigate the possibility of unique and overlapping rGMV correlates of inter-individual differences in social threat and reward expectancies (STE and SRE, respectively) as measured by the LODESTARS.…”

Brain structure correlates of expected social threat and reward

“…Reduced vividness of positive future thinking is characteristic of anxious as well as depressed individuals, in addition to anxious expectancies about future social interactions unique to anxiety 72 . Social anxiety can be regarded as a position along a continuum ranging from a lack of anxiety, to mild shyness and then social anxiety disorder (SAD) 15,16,85 , so our findings can meaningfully be compared with studies of SAD, which show reduced vmPFC volume 86,87 .…”

“…pSTS rGMV is increased in SAD and shyness (e.g. 87,94 ), and increased pSTS activity to social perceptual cues (eye gaze etc.) has been consistently demonstrated in individuals who are social inhibited, shy, and socially anxious [95][96][97][98] .…”

Aberrant Gray Matter Networks in Non-comorbid Medication-Naive Patients With Major Depressive Disorder and Those With Social Anxiety Disorder

“…The postcentral gyrus also plays an important role in emotional processing, including the identification of emotional significance in a stimulus, generation of emotional states, and regulation of emotion (Kropf et al, 2018). Studies have revealed increased resting-state and task-related activities in the occipital cortex in SAD, which might underlie the enhanced environmental scanning for potentially threatening or feared stimuli in SAD (Wang et al, 2018). Cortical thinning in the postcentral region was functionally related to the severity of social anxiety symptoms in SAD (Syal et al, 2012).…”