Increased structural covariance of cortical measures in individuals with an at-risk mental state

An anomalous pattern of structural covariance has been reported in schizophrenia, which has been suggested to represent connectome changes during brain maturation and neuroprogressive processes. It remains unclear whether similar differences exist in a clinical high-risk state for psychosis, and if they are associated with a prodromal phenotype and/or later psychosis onset. This multicenter magnetic resonance imaging study cross-sectionally examined structural covariance in a large at-risk mental state (ARMS) sample with different outcomes. The whole-brain structural covariance of four cortical measures (thickness, area, volume, and gyrification) was assessed in 155 individuals with ARMS, who were subclassified into 26 (16.8 %) with a later psychosis onset (ARMS-P), 44 with persistent subthreshold psychotic symptoms, and 53 with the remission of psychotic symptoms (ARMS-R) during the clinical follow-up, and 191 healthy controls. The relationships of changes in structural covariance with clinical symptoms and cognitive impairments were also investigated in the ARMS subsample. Structural covariance was significantly higher in widespread cortical regions in the ARMS group than in the controls, with each cortical measure having a different pattern in affected cortical regions. The higher structural covariance of the cortical area was partly related to severe suspiciousness–persecutory ideation. Structural covariance was significantly higher, mainly in fronto-parietal gyrification, in the ARMS-P group than in the ARMS-R group. The present results suggest that changes in structural covariance result in psychosis vulnerability and the excessive structural covariance of brain gyrification in ARMS subjects may contribute to their later clinical course.