A multiscale characterization of cortical shape asymmetries in early psychosis

ABSTRACT Background Psychosis has often been linked to abnormal cortical asymmetry, but prior results have been inconsistent. Here, we applied a novel spectral shape analysis to characterize cortical shape asymmetries in patients with early psychosis across different spatial scales. Methods We used the Human Connectome Project for Early Psychosis dataset (aged 16–35), including 56 healthy controls (male = 37, female = 19) and 112 patients with early psychosis (male = 68, female = 44). We quantified shape variations of each hemisphere over different spatial frequencies and applied a generalized linear model to compare differences between healthy control participants and patients with early psychosis. We further used a canonical correlation analysis (CCA) to examine associations between shape asymmetries and clinical symptoms. Results Cortical shape asymmetries, spanning wavelengths between about 22 mm and 75 mm, were significantly different between healthy control participants and patients with early psychosis (Cohen’s d = 0.28−0.51), with patients showing greater asymmetry in cortical shape than controls. A single canonical mode linked the asymmetry measures to symptoms (CCA r = 0.45), such that higher cortical asymmetry was correlated with more severe excitement symptoms and less severe emotional distress. In contrast, significant group differences in morphological asymmetries of cortical thickness, surface area, and gyrification at either global or regional levels were not identified. Conclusions Cortical shape asymmetries are more sensitive than other morphological asymmetries in capturing abnormalities in patients with early psychosis. These abnormalities are expressed at coarse spatial scales and are correlated with specific symptom domains. Highlights Cortical shape asymmetries are more sensitive than other cortical asymmetry measures, such as cortical thickness, surface area and gyrification, in capturing abnormalities in patients with early psychosis. The abnormalities in cortical shape asymmetry are expressed at coarse spatial scales and are correlated with excitement and emotional distress symptoms.