Evidence for abnormalities of cortical development in adolescent-onset schizophrenia

Abstract

Voxel-Based Morphometry (VBM) identifies differences in grey matter brain structure in patients with schizophrenia relative to healthy controls, with particularly prominent differences found in patients with the more severe, adolescent-onset form of the disease. However, as VBM is sensitive to a combination of changes in grey matter thickness, intensity and folding, specific neuropathological interpretations are not possible. Here, we attempt to more precisely define cortical changes in 25 adolescent-onset schizophrenic patients and 25 age- and sex-matched healthy volunteers using Surface-Based Morphometry (SBM) to disambiguate the relative contributions of cortical thickness and surface area differences to changes in regional grey matter (GM) density measured with VBM. Cortical changes in schizophrenia were widespread, including particularly the prefrontal cortex and superior temporal gyrus. Nine regions of apparent reduction in GM density in patients relative to healthy matched controls were found using VBM that were not found with SBM-derived cortical thickness measures. In Regions of Interest (ROIs) derived from the VBM group results, we confirmed that local surface area differences accounted for these VBM changes. Our results emphasize widespread, but focally distinct cortical pathology in adolescent-onset schizophrenia. Evidence for changes in local surface area (as opposed to simply cortical thinning) is consistent with a neurodevelopmental contribution to the underlying neuropathology of the disease.