Dysfunction of Resting-State Functional Connectivity of Amygdala Subregions in Drug-Naïve Patients With Generalized Anxiety Disorder

Abstract

Objective: Although previous studies have reported on disrupted amygdala subregional functional connectivity in generalized anxiety disorder (GAD), most of these studies were conducted in GAD patients with comorbidities or with drug treatment. Besides, whether/how the amygdala subregional functional networks were associated with state and trait anxiety is still largely unknown. Methods: Resting-state functional connectivity of amygdala subregions, including basolateral amygdala (BLA) and centromedial amygdala (CMA) as seed, were mapped and compared between 37 drug-naïve, non-comorbidity GAD patients and 31 age- and sex-matched healthy controls (HCs). Relationships between amygdala subregional network dysfunctions and state/trait anxiety were examined using partial correlation analyses. Results: Relative to HCs, GAD patients showed weaker functional connectivity of the left BLA with anterior cingulate/medial prefrontal cortices. Significantly increased functional connectivity of right BLA and CMA with superior temporal gyrus and insula were also identified in GAD patients. Furthermore, these functional connectivities showed correlations with state and trait anxiety scores. Conclusions: These findings revealed abnormal functional coupling of amygdala subregions in GAD patients with regions involved in fear processing and emotion regulation, including anterior cingulate/medial prefrontal cortex and superior temporal gyrus, which provide the unique biological markers for GAD and facilitating the future accurate clinical diagnosis and target treatment.

Keywords: amygdala; generalized anxiety disorder; resting-state functional connectivity; state anxiety; trait anxiety.

Figure 1

Left basolateral amygdala (BLA) functional connectivity (upper left panel) in generalized anxiety disorder (GAD) patients (first row) and in healthy controls (HCs; second row), and group differences shown in the third row. Compared with HCs, GAD patients showed weaker functional connectivity between the left BLA and anterior cingulate/medial prefrontal cortices (see bar graph in lower left panel). As shown in the scatterplot (right panel), a weaker FC between the left BLA and anterior cingulate/medial prefrontal cortices is associated with a higher-state anxiety and trait anxiety score in the sample as a whole.

Figure 2

Group comparisons in FC of the right basolateral amygdala (BLA) (upper panel) and right centromedial amygdala (CMA) (lower panel) revealed relatively similar results. GAD patients exhibited significantly increased right BLA/CMA functional connectivity with a cluster including the superior temporal gyrus and insula. Additionally, the scatterplot showed positive associations between FC and State Anxiety Inventory (SAI)/Trait Anxiety Inventory (TAI) in the sample as a whole.