Abstract
This study compared the topological organization of brain function in never-treated and treated long-term schizophrenia patients. In a cross-sectional study, 21 never-treated schizophrenia patients with illness duration over 5 years, 26 illness duration-matched antipsychotic-treated patients and 24 demographically-matched healthy controls underwent a resting-state functional magnetic resonance imaging (MRI) scan. The topological properties of brain functional networks were compared across groups, and then we tested for differential age-related effects in regions with significant group differences. Both never-treated and antipsychotic-treated schizophrenia patient groups showed altered nodal centralities in left pre-/postcentral gyri relative to controls. Never-treated patients demonstrated reduced global efficacy, decreased nodal centralities in right amygdala/hippocampus and bilateral putamen/caudate relative to antipsychotic-treated patients and controls. No significant relationships of age and altered functional metrics were seen in either patient group, and no alterations were greater in the treated group. These findings provide insight into brain function deficits over the longer-term course of schizophrenia independent from potential effects of antipsychotic medication. The presence of greater alterations in never-treated than treated patients suggests that long-term antipsychotic treatment may partially protect or enhance brain global and nodal topological function over the course of schizophrenia, notably involving the amygdala, hippocampus, and striatum that have long been associated with the disorder.