Distinct disruptions of resting-state functional brain networks in familial and sporadic schizophrenia.

Jiajia Zhu,Feng Liu,Lixue Xu,Chuanjun Zhuo,Chunshui Yu,Wen Qin

doi:10.1038/srep23577

Abstract

Clinical and brain structural differences have been reported between patients with familial and sporadic schizophrenia; however, little is known about the brain functional differences between the two subtypes of schizophrenia. Twenty-six patients with familial schizophrenia (PFS), 26 patients with sporadic schizophrenia (PSS) and 26 healthy controls (HC) underwent a resting-state functional magnetic resonance imaging. The whole-brain functional network was constructed and analyzed using graph theoretical approaches. Topological properties (including global, nodal and edge measures) were compared among the three groups. We found that PFS, PSS and HC exhibited common small-world architecture of the functional brain networks. However, at a global level, only PFS showed significantly lower normalized clustering coefficient, small-worldness, and local efficiency, indicating a randomization shift of their brain networks. At a regional level, PFS and PSS disrupted different neural circuits, consisting of abnormal nodes (increased or decreased nodal centrality) and edges (decreased functional connectivity strength), which were widely distributed throughout the entire brain. Furthermore, some of these altered network measures were significantly correlated with severity of psychotic symptoms. These results suggest that familial and sporadic schizophrenia had segregated disruptions in the topological organization of the intrinsic functional brain network, which may be due to different etiological contributions.

Highlights

Graph theory provides a powerful theoretical framework for characterizing topological properties of brain networks[23,24,25]
In the defined threshold range, functional brain networks of the patients with familial schizophrenia (PFS), patients with sporadic schizophrenia (PSS) and healthy controls (HC) exhibited higher clustering coefficients (i.e., γ > 1) but almost identical characteristic path lengths (i.e., λ ≈ 1) relative to comparable random networks, which indicates that the three groups showed a typical small-world topology (i.e., σ > 1) (Fig. S1)
Three main findings are revealed: (1) at a global level, only the PFS showed significantly lower values in normalized clustering coefficient, small-worldness, and local efficiency, implying a randomization shift of their brain networks; (2) at a regional level, PFS and PSS disrupted different neural circuits, suggesting distinct neural mechanisms between the two subgroups; and (3) these altered network measures were significantly correlated with severity of psychotic symptoms, indicating potential biomarkers of the subtypes of the disorder

Summary

Introduction

Graph theory provides a powerful theoretical framework for characterizing topological properties of brain networks[23,24,25]. A systematical investigation on differences in the topological organization of the brain functional networks between familial and sporadic schizophrenia will facilitate a more sophisticated understanding of the neuropathological mechanisms of the two subtypes of schizophrenia. On the basis of great differences in clinical symptoms[5,6,7,8] and brain properties[17,18,19,20,21,22] between the two subtypes of schizophrenia, we hypothesize that familial and sporadic schizophrenia would show segregated disruptions in the topological organization of intrinsic functional brain networks. Inter-group differences in the topological properties of the networks and their relationships with psychotic symptoms were investigated

Methods

Results

Conclusion