White matter diffusivity and microarchitecture among schizophrenia subjects and first-degree relatives

Background: Impairments in structural and functional connections are demonstrated in schizophrenia. Certain disconnectional patterns may be biomarkers of elevated risk for schizophrenia. Convergent examination of multiple diffusion parameters and cognitive performance better illustrates pathophysiological significance of such disconnectional patterns. Methods: Diffusion Tensor Imaging data on 39 early-course schizophrenia subjects, 21 adolescent/young adult first-degree relatives (FDR) of schizophrenia subjects and 29 healthy controls (HC) were examined for threshold-free clusters of fractional anisotropy (FA) and radial diffusivity (RD) differences correcting for multiple comparisons. Regression models examined the variance contributed by anisotropy differences, age and sex. Group-wise differences on sustained attention, verbal memory and executive functions were examined and correlated with diffusivity measures controlling for age and sex. Results: Schizophrenia subjects showed significantly decreased FA and increased RD in the forceps minor and superior longitudinal fasciculus (SLF) compared to HC. FDR showed decreased forceps minor FA compared to HC, and decreased SLF RD compared to HC and schizophrenia subjects. Quantitative RD differences were 2-3 fold higher compared to FA. Besides, forceps minor RD was inversely correlated with sustained attention in schizophrenia. Conclusions: Schizophrenia and FDR subjects show different patterns of white matter diffusivity compared to HC. While forceps minor changes may be a disease marker, SLF changes may be risk markers. In addition, RD may be a more robust risk marker than FA. (C) 2014 Elsevier B.V. All rights reserved.