A 2-year longitudinal investigation of insula subregional volumes in early psychosis.

Background: The insula is a heterogeneous cortical region with three cytoarchitectural subregions-agranular, dysgranular, and granular-that have distinct functional roles. Previous cross-sectional studies have shown smaller volume of all insula subregions in individuals with psychotic disorders. However, longitudinal trajectories of insula subregions in early psychosis, and the relationship between subregional volumes and relevant clinical phenomena, such as perceptual aberrations, have not been previously examined. Methods: 66 early psychosis (EP) and 65 healthy comparison (HC) participants completed 2-4 study visits over 2 years. T1-weighted structural brain images were processed using longitudinal voxel-based morphometry in CAT12 and segmented into anatomic subregions. At baseline, participants completed the Perceptual Aberrations Scale (PAS) to capture bodily distortions. The EP group was further examined based on diagnostic trajectory over two years (stable schizophrenia, stable schizophreniform, and conversion from schizophreniform to schizophrenia). Results: EP participants had smaller insula volumes in all subregions compared to HC participants, and these volumes were stable over two years. Compared to HC, insula volumes were significantly smaller in EP participants with a stable diagnosis of schizophrenia, but other diagnostic trajectory groups did not significantly differ from HC or the stable schizophrenia group. While perceptual aberrations were significantly elevated in EP participants, PAS scores were not significantly related to insula volume. Conclusions: We find that all insula subregions are smaller in early psychosis and do not significantly decline over two years. These data suggest that all insula subregions are structurally impacted in schizophrenia-spectrum disorders and may be the result of abnormal neurodevelopment.