Abstract: Objective · To explore the role of functional connectivity (FC) within the fronto-limbic network in predicting the onset of psychosis in the subjects with clinical high-risk for psychosis (CHR). Methods · A total of 164 CHR subjects and 89 healthy controls (HC) who underwent resting-state functional MRI were recruited. FCs between frontal [medial prefrontal cortex and bilateral orbitofrontal cortex (OFC)] and limbic (bilateral hippocampus and bilateral amygdala) brain regions at baseline were calculated. CHR subjects were further divided into 3 subgroups, i.e., CHR converters (CHR-C) group, symptomatic CHR (CHR-S) group and remitted CHR (CHR-R) group according to clinical outcome after one-year follow-up. The FCs of fronto-limbic network were compared between the groups and among the subgroups, and their interaction with brain regions, as well as their correlations with positive and negative symptoms were analyzed. Results · There was no significant main effect of group (P=0.110), but a significant interaction of subgroups and brain regions (P=0.049). CHR-C group had lower FC between bilateral OFC and bilateral amygdala than HC group and CHR-R group (all P<0.05). The FCs between left OFC and left hippocampus in the three CHR subgroups were all lower than that in HC group (all P<0.05). In addition, the FC between left OFC and right amygdala was positively correlated with the severity of negative symptoms in CHR-C group, while the FCs between left OFC and bilateral hippocampus and between right OFC and left hippocampus were negatively correlated with the severity of positive symptoms in CHR-C group. Conclusion · The decrease of OFC-hippocampus connectivity may be common in the subjects with CHR, while the decrease of OFC-amygdala connectivity may predict CHR subjects will convert to schizophrenia in the later stage.

Key words: clinical high-risk for psychosis (CHR), fronto-limbic network, functional connectivity, schizophrenia