A longitudinal study on intrinsic connectivity of hippocampus associated with positive symptom in first-episode schizophrenia

• SCZ exaggerated the disconnection between hippocampus and many cerebral cortexes.
• There was an interaction effect of group and time for FC with several regions.
• Longitudinal changes of hippocampal FC with MFG correlated with positive symptom.

Hippocampal pathology has been considered to underlie clinical, functional and cognitive impairments in schizophrenia. While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the hippocampus during the early phases of schizophrenia (SCZ), very little is known about whether functional connectivity (FC) between the hippocampus and other brain regions also exhibit progressive changes. In this study, resting state functional MRI (fMRI) was used to examine changes in hippocampal connectivity at baseline and follow-up scans comparing 68 patients with first episode SCZ and 62 matched controls. At baseline and follow-up, in the bilateral hippocampal network, SCZ mainly showed decreased FC with bilateral cerebellum posterior lobe, frontal gyrus temporal gyrus, precuneus, and cingulate cortex compared to controls. Furthermore, in the bilateral hippocampus, there was a significant interaction effect of group and time for FC with cerebellum posterior lobe, temporal gyrus, frontal gyrus, and posterior cingulate cortex. Interestingly, longitudinal changes of bilateral hippocampal connectivity with right middle frontal gyrus negatively correlated with positive symptom scores in SCZ. These results provide novel evidence for the progressive changes of FC between hippocampus and other brain regions in SCZ. It further suggests that longitudinal changes of bilateral hippocampal connectivity with right middle frontal gyrus can contribute to the formation and emergence of positive symptom of SCZ.