Dynamic changes of functional segregation and integration in vulnerability and resilience to schizophrenia
Schizophrenia (SZ) is a highly heritable disease with neurodevelopmental origins and significant
functional brain network dysfunction. Functional network is heavily influenced by neurodeve-
lopment processes and can be characterized by the degree of segregation and integration. This
study examines functional segregation and integration in SZ and their first-degree relatives (high
risk [HR]) to better understand the dynamic changes in vulnerability and resiliency, and disease
markers. Resting-state functional magnetic resonance imaging data acquired from 137 SZ,
89 HR, and 210 healthy controls (HCs). Small-worldness σ was computed at voxel level to quan-
tify balance between segregation and integration. Interregional functional associations were
examined based on Euclidean distance between regions and reflect degree of segregation and
integration. Distance strength maps were used to localize regions of altered distance-based
functional connectivity. σ was significantly decreased in SZ compared to HC, with no differences
in high risk (HR). In three-group comparison, significant differences were noted in short-range
connectivity (primarily in the primary sensory, motor and their association cortices, and the
thalamus) and medium/long-range connectivity (in the prefrontal cortices [PFCs]). Decreased
short- and increased medium/long-range connectivity was found in SZ. Decreased short-range
connectivity was seen in SZ and HR, while HR had decreased medium/long-range connectivity.
We observed disrupted balance between segregation and integration in SZ, whereas relatively
preserved in HR. Similarities and differences between SZ and HR, specific changes of SZ were
found. These might reflect dynamic changes of segregation in primary cortices and integration in
PFCs in vulnerability and resilience, and disease markers in SZ.

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