Impaired Interactions Among White-Matter Functional Networks in Antipsychotic-Naive First-Episode Schizophrenia

Abstract

Background: Schizophrenia has been conceptualized as a disorder arising from structurally pathological alterations to white-matter fibers in the brain. However, few studies have focused on white-matter functional changes in schizophrenia. Considering that converging evidence suggests that white-matter resting state functional MRI (rsfMRI) signals can effectively depict neuronal activity and psychopathological status, this study examined white-matter network-level interactions in antipsychotic-naive first-episode schizophrenia (FES) to facilitate the interpretation of the psychiatric pathological mechanisms in schizophrenia. Methods: We recruited a total of 106 participants from two independent cohorts including 55 FES patients (FESs) and 51 healthy controls (HCs), all of whom underwent rsfMRI. We identified 11 white-matter functional networks, which could be further classified into deep, middle, and superficial layers of networks. We then examined network-level interactions among these 11 white-matter functional networks using Granger causality analysis. We employed group comparisons on the influences among 11 networks using network-based statistic. Outcomes: In the primary cohort, excitatory influences from the middle superior corona radiate network to the superficial orbitofrontal and deep networks were disrupted in FESs compared with HCs. Additionally, an extra failure of suppression within superficial networks (including the pre/post-central network, temporofrontal network, and the orbitofrontal network) was observed in FESs. Similar replication results of an independent sample further verified the middle network disengagement in the white-matter network interaction model of FES. Interpretations: The novel findings of impaired interactions among white-matter functional networks in schizophrenia indicate that the pathophysiology of schizophrenia may also lie in white-matter functional abnormalities. Funding Statement: This work was supported by the National Natural Science Foundation of China (61533006, 81471653, 81771919, 61673089 and U1808204), China Postdoctoral Science Foundation (2013M532229), Sichuan Science and Technology Program (2018TJPT0016), and the “111” project (B12027). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of the Second Affiliated Hospital of Xinxiang Medical University, China.