A two-year longitudinal investigation of insula subregional cortical thickness and surface area in early psychosis

Smaller insula volume is consistently observed in psychotic disorders; however, alterations in associated cortical features-thickness and surface area-are less clear. We examined insula thickness and surface area changes in early psychosis to determine whether alterations were a) present in the early stages of psychosis, b) specific to any of the insula's three cytoarchitectural subregions (agranular, dysgranular, and granular) and c) related to behaviors impacted in psychosis. 63 non-affective early psychosis (EP) and 59 healthy comparison (HC) participants completed 2-4 study visits over two years. Cortical thickness and surface area was quantified via T1 MRI and segmented into three anatomic subregions: anterior (agranular), middle (dysgranular), and posterior (granular). Perceptual aberrations, cognition, and psychotic symptoms were measured; group differences and longitudinal changes were tested using linear mixed models. EP participants had lower cortical thickness in all insula subregions and thickness declined at a normative rate, compared to HC participants. Insula surface area, on the other hand, was intact in EP and also showed a normative pattern of decline over two years. No significant associations were observed between structural metrics and clinical phenotypes. In early psychosis, insula cortical thickness, but not surface area, is disrupted, and demonstrates normative changes over two years. This pattern is observed for all insula subregions. These data suggest that cortical thickness of the insula is structurally impacted in schizophrenia-spectrum disorders and may be the result of abnormal neurodevelopment occurring prior to illness onset.