Alterations in Cortical Thickness in Anxiety Disorders and Their Association with Atlas-Based Neurotransmitter Maps

Neuroimaging studies have revealed that anxiety disorders (ADs) have been associated with altered cortical thickness (CTh) in some key brain regions, but findings are inconsistent and the molecular basis of structural damage remains unknown. Here, the aim of this study was to identify the most consistent CTh alterations in ADs and to characterize their underlying molecular features.

A comprehensive meta-analysis was conducted to identify consistent CTh alterations in patients with ADs by using anisotropic effect-size seed-based d mapping (AES-SDM) software. On this basis, spatial correlations between neurotransmitter distribution data and the CTh alterations were investigated using the JuSpace toolbox, thereby revealing the neural mechanisms underlying ADs from a cross-modal perspective.

A total of 9 studies comprising 264 patients with ADs and 286 healthy controls (HCs) were included. Compared with HCs, ADs showed increased CTh in the left precentral gyrus (PreCG) and left insula and decreased CTh in the dorsolateral region of the right superior frontal gyrus. In meta-regression analyses, the CTh alterations in the left PreCG were negatively correlated with the mean age and percentage of males in the patients, respectively. The pattern of structural alterations associated with ADs was also correlated with the distribution of serotonergic, GABAergic, cholinergic, and glutamatergic neurotransmitters.

By linking abnormal CTh to specific neurotransmitter systems, this work advances an integrative understanding of the morphological alterations in ADs and their molecular basis, which provides clues to potential therapeutic targets.

This meta-analysis revealed consistent CTh abnormalities in sensorimotor cortex, limbic system, and dlPFC regions in ADs, correlating with multiple neurotransmitter distributions. While offering initial insights into complex neuropathogenesis and potential therapeutic targets, these findings remain preliminary and need to be validated through larger-scale, multimodal studies in well-defined phenotypic cohorts.