Default mode network connectivity is associated with long-term clinical outcome in patients with schizophrenia

Abstract

This study investigated whether resting-state functional connectivity is associated with long-term clinical outcomes of patients with schizophrenia. Resting-state brain images were obtained from 79 outpatients with schizophrenia and 30 healthy controls (HC), using a 3 T-MRI scanner. All patients were 20-50 years old with >3 years' duration of illness and appeared clinically stable. We assessed their psychopathology using the 18-item Brief Psychiatric Rating Scale (BPRS-18) and divided them into "good," "moderate," and "poor" outcome (SZ-GO, SZ-MO, and SZ-PO) groups depending on BPRS-18 total score. We obtained individual functional connectivity maps between a seed region of the bilateral posterior cingulate cortex (PCC) and all other brain regions and compared the functional connectivity of the default mode network (DMN) among the HC and 3 schizophrenia outcome groups, with a voxel-wise threshold of P < .001 within a cluster-extent threshold of 114 voxels. Additionally, we assessed correlations between functional connectivity and BPRS-18 scores. The SZ-MO and SZ-PO groups showed decreased functional connectivity between PCC and right ventromedial prefrontal cortex (vmPFC), left middle cingulate cortex, and left frontopolar cortex (FPC) compared to the SZ-GO and HC groups. DMN connectivity in the right vmPFC and left FPC negatively correlated with subscale scores of the BPRS-18, except the negative symptoms subscale. In this study, poorer clinical outcomes in patients with schizophrenia were associated with decreased DMN connectivity. In particular, the decreased functional connectivity might be related to the severity of positive and mood symptoms rather than negative symptoms.

Keywords: Default mode network; Functional connectivity; Outcome; Resting-state; Schizophrenia.

Fig. 1

Brain areas showing functional connectivity with the seed region of the bilateral posterior cingulate cortex. Abbreviations: HC, healthy controls; SZ-GO, schizophrenia patients with good outcome; SZ-MO, schizophrenia patients with moderate outcome; SZ-PO, schizophrenia patients with poor outcome.

Fig. 2

Group comparisons of default mode network connectivity using analysis of covariance and Bonferroni post-hoc test. Red circles indicate (a) right ventromedial prefrontal cortex, (b) left middle cingulate cortex, and (c) left frontopolar cortex, the regions showing significant differences in functional connectivity with the seed region of the bilateral posterior cingulate cortex. The group difference brain maps are superimposed onto the MNI152 T1 template. Abbreviations: HC, healthy controls; SZ-GO, schizophrenia patients with good outcome; SZ-MO, schizophrenia patients with moderate outcome; SZ-PO, schizophrenia patients with poor outcome. *Post-hoc P < .05, **post-hoc P < .001.