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Dysfunction of Resting-State Functional Connectivity of Amygdala Subregions in Drug-Naive 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.

SUBMITTER: Wang M

PROVIDER: S-EPMC8548605 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: The amygdala plays a key role in emotional hyperreactivity in response to social threat in patients with social anxiety disorder (SAD). We investigated resting-state functional connectivity (rs-FCN) of the left and right amygdala with various brain regions and functional lateralization in patients with SAD. Methods: A total of 36 patients with SAD and 42 matched healthy controls underwent functional magnetic resonance imaging (fMRI) at rest. Using the left and right amygdala as seed regions, we compared the strength of the rs-FCN in the patient and control groups. Furthermore, we investigated group differences in the hemispheric asymmetry of the functional connectivity maps of the left and right amygdala. Results: Compared with healthy controls, the rs-FCN between the left amygdala and the dorsolateral prefrontal cortex was reduced in patients with SAD, whereas left amygdala connectivity with the fusiform gyrus, anterior insula, supramarginal gyrus, and precuneus was increased or positively deflected in the patient group. Additionally, the strength rs-FCN between the left amygdala and anterior insula was positively associated with the severity of the fear of negative evaluation in patients with SAD (r = 0.338, p = 0.044). The rs-FCN between the right amygdala and medial frontal gyrus was decreased in patients with SAD compared with healthy controls, whereas connectivity with the parahippocampal gyrus was greater in the patient group than in the control group. The hemispheric asymmetry patterns in the anterior insula, intraparietal sulcus (IPS), and inferior frontal gyrus of the patient group were opposite those of the control group, and functional lateralization of the connectivity between the amygdala and the IPS was associated with the severity of social anxiety symptoms (r = 0.365, p = 0.037). Conclusion: Our findings suggest that in addition to impaired fronto-amygdala communication, the functional lateralization of amygdala function plays a central role in the pathophysiology of SAD.

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

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