Heterogeneous Brain Atrophy Sites in Anxiety Disorders Map to a Common Brain Network

Abstract

Background. Heterogeneous findings among anxiety disorder studies have hindered elucidation of the underlying pathophysiology and the development of mechanism-based therapies. Purpose. To determine whether structural MRI findings in anxiety disorder studies converge on a common network with therapeutic significance. Materials and Methods. In this retrospective study, a systematic literature search of PubMed and Web of Science databases was performed to identify coordinates of gray matter atrophy in patients with anxiety disorder. Atrophy coordinates were then mapped to an anxiety network constructed from the resting-state functional MRI (rs-fMRI) data of 652 healthy participants using “coordinate network mapping” and validated by specificity tests. The causal association of this network to anxiety symptoms was tested in a cohort of patients with brain lesions and emergent anxiety symptoms. The potential therapeutic utility of this anxiety network was then assessed by examining the clinical efficacy of network-targeted repetitive transcranial magnetic stimulation (rTMS) among a separate anxiety disorder cohort. Statistical analyses of images were performed using nonparametric tests and corrected for family-wise error. Results. Sixteen studies comprising 453 patients with anxiety (245 females; $\text{mean}\text{age}\pm \left[\text{SD}\right]$, $31.4\pm 8.71$ years) and 460 healthy controls (238 females; $31.7\pm 10.08$ years) were included in the analysis. Atrophy coordinates were mapped to an anxiety network with a hub region situated primarily within the superficial amygdala. Lesions associated with emergent anxiety symptoms exhibited stronger connectivity within this anxiety network than lesions not associated with anxiety ($t=2.99$; $P=.004$). Moreover, the connectivity strength of rTMS targets in the anxiety network was correlated with the improvements of anxiety symptom after treatment ($r=.42$, $P=.02$). Conclusions. Heterogeneous gray matter atrophy among patients with anxiety disorder localize to a common network that may serve as an effective therapeutic target.