Disruption of brain anatomical networks in schizophrenia: A longitudinal, diffusion tensor imaging based study

Abstract Despite convergent neuroimaging evidence indicating a wide range of brain abnormalities in schizophrenia, our understanding of alterations in the topological architecture of brain anatomical networks and how they are modulated over time, is still rudimentary. Here, we employed graph theoretical analysis of longitudinal diffusion tensor imaging data (DTI) over a 5-year period to investigate brain network topology in schizophrenia and its relationship with clinical manifestations of the illness. Using deterministic tractography, weighted brain anatomical networks were constructed from 31 patients experiencing schizophrenia and 28 age- and gender-matched healthy control subjects. Although the overall small-world characteristics were observed at both baseline and follow-up, a scan-point independent significant deficit of global integration was found in patients compared to controls, suggesting dysfunctional integration of the brain and supporting the notion of schizophrenia as a disconnection syndrome. Specifically, several brain regions (e.g., the inferior frontal gyrus and the bilateral insula) that are crucial for cognitive and emotional integration were aberrant. Furthermore, a significant group-by-longitudinal scan interaction was revealed in the characteristic path length and global efficiency, attributing to a progressive aberration of global integration in patients compared to healthy controls. Moreover, the progressive disruptions of the brain anatomical network topology were associated with the clinical symptoms of the patients. Together, our findings provide insights into the substrates of anatomical dysconnectivity patterns for schizophrenia and highlight the potential for connectome-based metrics as neural markers of illness progression and clinical change with treatment.