Meta-analysis of amygdala connectivity in anxiety disorders versus healthy controls

BACKGROUND: Anxiety disorders are associated with disrupted amygdala connectivity; however, resting-state functional MRI studies have reported heterogeneous findings. To clarify these inconsistencies, we conducted a meta-analysis of amygdala-based connectivity studies. METHODS: A systematic search of Embase, PubMed, and Web of Science was performed through December 26, 2025. Studies comparing amygdala-based whole-brain resting-state functional connectivity in patients with anxiety disorders versus healthy controls were included. Meta-analysis was conducted with the latest software - Seed-based d Mapping with Permutation of Subject Images (SDM-PSI), which employs voxel-wise tests and multiple corrections to minimize false positives. Subgroup analyses were performed to examine differences by age and hemisphere. RESULTS: Fifteen datasets (378 patients, 405 controls) were included. Compared to healthy controls, patients with anxiety disorders had decreased amygdala-anterior cingulate cortex (ACC,  = -0.54, 95% confidence interval [CI]: -0.73 to -0.35) connectivity and increased connectivity with the left superior temporal gyrus ( = 0.46, 95% CI: 0.27-0.65), middle temporal gyrus ( = 0.38, 95% CI: 0.19-0.57), and cuneus ( = 0.35, 95% CI: 0.17-0.53). After threshold-free cluster enhancement correction, only reduced amygdala-ACC connectivity remained significant ( = -0.54, 95% CI: -0.73 to -0.35). Subgroup analyses confirmed this effect was driven mainly by adult patients and the left amygdala. CONCLUSIONS: Reduced connectivity between the left amygdala and the ipsilateral ACC was the most robust neuroimaging marker of anxiety disorders, which suggests a lateralized vulnerability. By applying updated analytic methods, this study refines our understanding of the neuropathology of anxiety disorders and provides a potential primary target for biomarker development and novel interventions.