Psychosis Multiscale Functional Network Connectivity Subspace Encodes Sex Specificity and Identifies Sex Biotypes

Psychosis is a functionally disruptive condition, however little is known about the varying connectivity between different sexes and the extent of its variability. Resting-state fMRI (rsfMRI) data from the BSNIP consortium involving 626 controls (CON) and 1127 psychosis (PSY) participants (873 Females and 719 Males) were analyzed. Multiscale functional network connectivity (msFNC) for each subject was extracted by applying multivariate objective optimization ICA with Neuromark 2.2 data-driven reference template. The principal component space of PSY msFNC was then identified, within which sex specificity was uncovered. Our analysis revealed 4 statistically significant sex biotypes, 2 female dominant and 2 male dominant ones with unique connectivity characteristics. Psychosis dysconnectivity along cerebellar-subcortical regions was more prominent in males than females. These biotype findings highlight the manifestations of psychosis across different sexes with varying connectivity deficits relative to CON.