Progressive structural alterations associated with negative symptoms in schizophrenia: A causal structural covariance network analysis

Backgrounds: Aberrant brain structures in schizophrenia have been widely explored. However, the causal effects of negative symptoms on brain structural alterations are still unclear. This study aims to explore the synchronous and progressive alterations in gray matter volume (GMV) associated with negative symptoms. Methods: 81 Deficit schizophrenia (DS) patients, 101 non-deficit schizophrenia (NDS) patients, and 177 healthy controls (HCs) were enrolled in this study. T1-weighted images were collected, and the severity of clinical symptoms in patients was evaluated. Then voxel-based morphometry and source-based morphometry were used for gray matter segmentation and structural covariance network construction. Finally, DS patients were ranked based on the severity of negative symptoms, and a causal structural covariance network (CaSCN) was constructed using Granger causality analysis. Results: Twenty-four independent components were identified. Among them, 20 components showed smaller GMV in patients with schizophrenia compared to HCs. Furthermore, DS exhibited decreased GMV in right inferior frontal gyrus triangular part, bilateral para-hippocampal gyrus, and bilateral anterior cerebellum compared to NDS. Both patient groups showed increased structural covariance across various brain regions compared to HCs. Additionally, DS exhibited decreased structural covariance in left middle frontal gyrus, bilateral inferior frontal gyrus and right superior frontal gyrus compared to NDS. In CaSCN, as negative symptoms worsened, the volume of bilateral caudate decreased along with the atrophy of bilateral para-hippocampal gyrus, the volume of bilateral thalamus increased along with the decline in multiple brain regions, and the decreased volume of bilateral posterior cingulate cortex resulted in increased volume of bilateral lingual gyrus and other brain regions. Conclusions: The present study demonstrated the specific brain structural covariance patterns in DS, providing new evidence for the causal effects of negative symptoms on progressive structural abnormalities in schizophrenia.