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.
Highlights
Generalized anxiety disorder (GAD) is a common anxiety disorder characterized by excessive, pervasive, and uncontrollable anxiety, with a lifetime prevalence of about 5.7% [1]
We aimed to explore the specific amygdala subregional functional connectivity alterations in drug-naïve, non-comorbidity patients with GAD compared with age- and sex-matched healthy controls (HCs)
Positive correlations between FC of centromedial amygdala (CMA) with the left superior temporal gyrus/insula and trait anxiety were found in the GAD group (r = 0.355, p = 0.046) (Supplementary Figure 1)
Summary
Generalized anxiety disorder (GAD) is a common anxiety disorder characterized by excessive, pervasive, and uncontrollable anxiety, with a lifetime prevalence of about 5.7% [1]. The CMA, in contrast, mainly receives modulatory inputs from the BLA and orbitofrontal cortex and projects to the brainstem, cerebellum, and hypothalamus for behavioral and physiological aspects of emotion processing and associative learning [11,12,13,14]. These connectivity patterns of amygdala subregions have been proven by tractography, task-based and resting-state functional magnetic resonance imaging [9, 10, 13]
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