Abnormal inter- and intra-hemispheric integration in male paranoid schizophrenia: a graph-theoretical analysis

BACKGROUND: The human brain is a complex network of regions that are structurally interconnected by white matter (WM) tracts. Schizophrenia (SZ) can be conceptualized as a disconnection syndrome characterized by widespread disconnections in WM pathways. AIMS: To assess whether or not anatomical disconnections are associated with disruption of the topological properties of inter- and intra-hemispheric networks in SZ. METHODS: We acquired the diffusion tensor imaging data from 24 male patients with paranoid SZ during an acute phase of their illness and from 24 healthy age-matched male controls. The brain FA-weighted (fractional anisotropy-weighted) structural networks were constructed and the inter- and intra-hemispheric integration was assessed by estimating the average characteristic path lengths (CPLs) between and within the left and right hemisphere networks. RESULTS: The mean CPLs for all 18 inter-and intra-hemispheric CPLs assessed were longer in the SZ patient group than in the control group, but only some of these differences were significantly different: the CPLs for the overall inter-hemispheric and the left and right intra-hemispheric networks; the CPLs for the interhemisphere subnetworks of the frontal lobes, temporal lobes, and subcortical structures; and the CPL for the intra- frontal subnetwork in the right hemisphere. Among the 24 patients, the CPL of the inter-frontal subnetwork was positively associated with negative symptom severity, but this was the only significant result among 72 assessed correlations, so it may be a statistical artifact. CONCLUSIONS: Our findings suggest that the integrity of intra- and inter-hemispheric WM tracts is disrupted in males with paranoid SZ, supporting the brain network disconnection model (i.e., the (‘)connectivity hypothesis(’)) of schizophrenia. Larger studies with less narrowly defined samples of individuals with schizophrenia are needed to confirm these results.