Characteristics of the Gray Matter Network in Untreated Schizophrenia Patients Across a Large Age Span

Background: Progressive volumetric changes in gray matter in schizophrenia patients have been reported, but how network-based gray matter changes develop with age remains to be addressed. Methods: A total of 362 subjects were recruited, including 210 healthy controls and 152 never-treated schizophrenia patients. All patients were divided into 4 subgroups by age — A1~A4 (16-24 years, 25-34 years, 35-44 years, ≥45 years). High-resolution T1 images of the brain were obtained with a 3.0 T MR scanner and preprocessed with FreeSurfer. The graphic gray matter network was constructed based on the correlation coefficient of the cortical thickness between each pair of regions within the Desikan-Killiany template. Network matrices were calculated for each patient subgroup and compared with matched healthy control subgroups to identify the network disorganization across different ages. Findings: Compared to the paired healthy controls, the schizophrenia patients in all subgroups showed common network property changes (i.e., decreased nodal centrality) in regions mainly within the default mode network (DMN) and salience network (SN). Some network matrices exhibited changes only in the later aging subgroups, including nodal centrality decreases in the left isthmus cingulate and right caudal anterior cingulate in patients over 25 and nodal centrality loss in the left precuneus in patients over 35 years of age. Conclusion: Decreased nodal centrality within the DMN and SN in schizophrenia patients across different age subgroups may represent a disease trait in schizophrenia, while network changes observed only in the older patients may represent brain impairments that are associated with illness progression. Funding Statement: Supported by the National Natural Science Foundation of China (Project Nos. 81671664 and 81621003), National Program for Support of Top-notch Young Professionals (Project No. W02070140), and 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (Project Nos. ZYYC08001 and ZYJC18020). Declaration of Interests: The authors report no financial relationships with commercial interests. Ethics Approval Statement: This study was approved by an ethics committee of West China Hospital of Sichuan University, and written informed consent was obtained from all subjects before participation.