Temporal Dynamics in Degree Centrality of Brain Functional Connectome in First-Episode Schizophrenia with Different Short-Term Treatment Responses: A Longitudinal Study

Abstract

Purpose: This study investigated temporal dynamics in degree centrality (DC) of the brain functional connectome in first-episode schizophrenia with different short-term treatment responses.

Methods: A total of 127 first-episode patients (FEPs) with schizophrenia and 133 healthy controls (HCs) were recruited in this study. All subjects underwent resting-state functional magnetic resonance imaging. FEPs were scanned at baseline (pretreatment) and at follow-up (posttreatment), while HCs were scanned only at baseline. The patients were exposed to naturalistic antipsychotic treatment for 12 weeks, and classified as schizophrenia responders (SRs) or nonresponders (NRs). Voxel-wise dynamic DC analyses were conducted among the SRs (n=75), NRs (n=52), and HCs (n=133) to assess temporal variability in functional connectivity across the entire neuronal network.

Results: The SRs and NRs showed dissimilar dynamic DC at baseline, with differences mainly involving the temporal lobe. Different DC alteration was observed in the left fusiform gyrus, right fusiform gyrus, left middle cingulate cortex, and left superior parietal gyrus in the SRs and NRs pre- and posttreatment. SRs group and NRs presented opposite changing patterns of dynamic DC in particular regions of the brain.

Conclusion: These findings indicate that dynamic DC abnormalities exist in unmedicated patients with schizophrenia. The NRs differed from the SRs in dynamic DC not only at baseline but in the characteristics of changes before and after treatment as well. Our study may contribute to understanding pathophysiology in schizophrenia with different treatment responses.

Keywords: degree centrality; dynamics; resting-state functional magnetic resonance imaging; schizophrenia; treatment response.

Figure 1

Differences in dynamic DC between FEPs (all patients) and HCs on two-sample t-test analysis at baseline.

Figure 2

Differences in dynamic DC among the three groups on one-way ANOVA analysis at baseline (upper) and post hoc comparisons of dynamic DC in ITG.L and MTG.L among the three groups (lower). *P<0.05.

Figure 3

Interaction effects of group and time of dynamic DC in SRs and NRs pre- and posttreatment on RMANOVA analysis (upper) and post hoc comparisons of changes in dynamic DC values before and after treatment in SR and NR (lower). *P<0.05.

Figure 4

Correlation of dynamic DC variability with clinical characteristics in all FEPs at baseline. (A) Dynamic DC of right cerebellum posterior lobe significantly correlated with totalPANSS score (r=0.38, P<0.0001). (B) Dynamic DC of right medial frontal cortex negatively correlated with total PANSS score (r=–0.34, P<0.001). (C) Dynamic DC of right postcentral gyrus negatively correlated with positive symptoms (r=–0.32, P<0.001) (D) Dynamic DC of right medial frontal cortex negatively correlated with PANSS general psychopathology (r=–0.35, P<0.0001).

Figure 5

Correlation of changes in dynamic DC variability with clinical treatment response in all FEPs. (A) Altered dynamic DC of right middle cingulate cortex (r=0.35, P<0.0001) significantly correlated with reduction in total PANSS scores. (B) Altered dynamic DC of left superior parietal cortex (r=0.37, P<0.0001) significantly correlated with reduction in total PANSS scores.