Objective: Cortical-limbic system neural circuit abnormalities are closely related to the onset of schizophrenia (SZ). The amygdala, hippocampus, cingulate, and prefrontal lobe are important components of the loop. In this study, we compared resting-state functional connectivity (rs-FC) between the amygdala/hippocampus and cingulate/prefrontal regions among patients with first-episode schizophrenia (FE-SZ), high risk populations with SZ (HR-SZ), and healthy controls (HCs). By discovering the abnormal pattern of the cortical-limbic system of SZ and HR-SZ, we attempted to elucidate the pathophysiological mechanism of SZ. Method: This study collected seventy-five FE-SZ patients, 59 HR-SZ, and 64 HCs. Analysis of variance and chi-square tests were used to analyze their demographic data. Analysis of covariance and post-hoc analysis were performed on the functional connectivity of the three groups. Finally, correlation analysis between the significant brain functional connectivity value and the scale score was performed. Results: The results of the analysis of covariance showed that there were significant differences in rs-FC between the amygdala and the right middle cingulate and between the hippocampus and the bilateral medial superior frontal gyrus among the three groups (Gaussian random field (GRF)-corrected voxel p < 0.001, cluster p < 0.05). Post hoc comparisons showed that the rs-FC of the amygdala-right middle cingulate and the hippocampus-bilateral medial superior frontal gyrus in patients with SZ was significantly lower than that of HR-SZ and HC (Bonferroni corrected p < 0.001). There was no significant difference between the HR-SZ and HC groups. The results of the correlation analysis showed that rs-FC of the hippocampus-medial frontal gyrus in patients with SZ was positively correlated with core depression factor scores on the Hamilton Depression Scale (P = 0.006, R = 0.357). Conclusion: There were different patterns of functional connectivity impairment in the amygdala and hippocampal neural circuits in the schizophrenic cortical-limbic system, and these patterns may be more useful than genetics as state-related imaging changes of the disease.

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