Diminished functional segregation and resilience are associated with symptomatic severity and cognitive impairments in schizophrenia: a large-scale study.

Background: The research findings on the topological properties of functional connectomes (TP-FCs) in patients with schizophrenia (SZPs) exhibit inconsistencies and contradictions, which can be attributed to limitations such as small sample sizes and heterogeneous data processing techniques. Aims: To address these limitations, we conducted a large-scale study. Uniform data processing flows were employed to investigate the aberrant TP-FCs and the associations between TP-FCs and symptoms or cognitions (A-TP-SCs) in SZPs. Methods: The large-scale study included six datasets from four sites, involving 497 SZPs and 374 healthy controls (HCs). A uniform process for imaging data preprocessing and functional connectivity matrix configuration was used. ComBat was employed for data harmonisation, and various TPs were calculated. We explored between-group differences in brain functional integration (FI) and functional segregation (FS) measured with TP-FCs, and conducted partial correlation analyses, with adjustments for age, gender and educational level, to identify A-TP-SCs. Results: Compared with random networks and HCs, SZPs maintained small-worldness and global FI capacity despite their compromised global FS capacity and resilience. A decline in nodal FI and FS capacity was observed in sensory areas, whereas an increase in nodal FI capacity was found in regions associated with cognition and information integration. In addition, associations between TP-FCs and positive symptoms, negative symptoms or cognitive functions including speed of processing, visual learning and the ability to inhibit cognitive interference were identified in SZPs. Conclusions: The identified A-TP-SCs verified that reductions in FS and resilience indicated pathological impairments in schizophrenia. The A-TP-SCs or TP-FCs, which measured the same attributes of the functional connectomes, exhibited high internal consistency, robustly reinforcing these findings.