Neurite Density and Kurtosis in the Gray Matter of People With Early Schizophrenia.

Abstract

Background: Classic models of diffusion-weighted imaging, especially diffusion tensor imaging, are unsuitable for application to the cortical gray matter given its high microstructural complexity. As such, most neuroimaging studies have focused on gross structural effects of schizophrenia, such as cortical thickness differences. More recently developed models, such as neurite orientation dispersion and density imaging (NODDI) and diffusion kurtosis imaging (DKI), incorporate higher-resolution data and may provide more sensitive descriptions of schizophrenia pathology with more specific interpretations.

Methods: We applied the NODDI and DKI models to the cortical gray matter of people with early schizophrenia (n = 54) and healthy control participants (n = 51) from the Human Connectome Project for Early Psychosis dataset. Comparisons between groups were made using region-of-interest and clustering approaches. The effect sizes of these approaches were compared with those of cortical thickness differences. We also investigated the relationship between these parameters and lifetime antipsychotic usage.

Results: Cortical thickness differences were most prominent between groups in terms of global effect size and spatial extent. We also observed a diffuse, right hemisphere-dominant increase in mean kurtosis and isotropic diffusion fraction throughout the gray matter, which was not fully explained by partial volume effects. Additionally, a lower neurite density index (NDI) correlated with greater lifetime antipsychotic usage.

Conclusions: Increases in mean kurtosis and isotropic diffusion fraction are both markers of schizophrenia, consistent with inflammation models of the gray matter in schizophrenia. NDI reduction, reflecting intraneurite pathology, becomes prominent only in individuals with greater disease burden.