Recent studies have increasingly utilized gradient metrics to investigate the spatial transitions of brain organization, enabling the conversion of macroscale brain features into low-dimensional manifold representations. However, it remains unclear whether alterations exist in the cortical morphometric similarity (MS) network gradient in patients with schizophrenia (SCZ). This study aims to examine potential differences in the principal MS gradient between individuals with SCZ and healthy controls and to explore how these differences relate to transcriptional profiles and clinical phenomenology.

MS network was constructed in this study, and its gradient of the network was computed in 203 patients with SCZ and 201 healthy controls, who shared the same demographics in terms of age and gender. To examine irregularities in the MS network gradient, between-group comparisons were carried out, and partial least squares regression analysis was used to study the relationships between the MS network gradient-based variations in SCZ, and gene expression patterns and clinical phenotype.

In contrast to healthy controls, the principal MS gradient of patients with SCZ was primarily significantly lower in sensorimotor areas, and higher in more areas. In addition, the aberrant gradient pattern was spatially linked with the genes enriched for neurobiologically significant pathways and preferential expression in various brain regions and cortical layers. Furthermore, there were strong positive connections between the principal MS gradient and the symptomatologic score in SCZ.

These findings showed changes in the principal MS network gradient in SCZ and offered potential molecular explanations for the structural changes underpinning SCZ.