Preserved white matter structure at the grey matter–white matter interface despite widespread cortical thinning in early psychosis

BACKGROUND: Early psychosis is characterized by widespread cortical grey matter (GM) reductions. White matter (WM) alterations have also been reported. The GM-WM interface may represent a link between cortical GM and WM alterations that remains understudied. As the interface matures later in development than deep WM, it may be particularly vulnerable to neurodevelopmental disruptions in schizophrenia-spectrum disorders. However, its complex fiber architecture and proximity to the cortex pose challenges for conventional diffusion tensor imaging. METHODS: We applied an advanced diffusion MRI approach to assess fiber density (FD) in the GM-WM interface of 78 individuals with early psychosis (age 22.0 ± 3.0, 29.5% female) and 78 controls (age 21.8 ± 3.2, 29.5% female). We examined group differences in FD at the GM-WM interface and cortical measures, and assessed spatial correlations between regional effect sizes of FD and cortical measures. RESULTS: Widespread cortical thinning was observed, whereas no significant group differences were identified in FD at the GM-WM interface. This finding remained robust after accounting for partial-volume effects and was consistent with the template-space analysis. The spatial distribution of FD effect sizes showed significant positive correlations with those of cortical thickness and surface area. CONCLUSIONS: Despite widespread cortical GM alterations, WM microstructure at the GM-WM interface was relatively preserved in early psychosis, while spatial correspondence between GM and WM measures at the interface was observed. These findings suggest that cortical alterations are pronounced in early psychosis, whereas WM changes may manifest later in the course of illness.