Mean diffusivity and fractional anisotropy as indicators of disease and genetic liability to schizophrenia

Abstract

The goals of this study were to first determine whether the fractional anisotropy (FA) and mean diffusivity (MD) of major white matter pathways associate with schizophrenia, and secondly to characterize the extent to which differences in these metrics might reflect a genetic predisposition to schizophrenia. Differences in FA and MD were identified using a comprehensive atlas-based tract mapping approach using diffusion tensor imaging and high-resolution structural data from 35 patients, 28 unaffected first-degree relatives of patients, 29 community controls, and 14 first-degree relatives of controls. Schizophrenia patients had significantly higher MD in the following tracts compared to controls: the right anterior thalamic radiations, the forceps minor, the bilateral inferior fronto-occipital fasciculus (IFO), the temporal component of the left superior longitudinal fasciculus (tSLF), and the bilateral uncinate. FA showed schizophrenia effects and a linear relationship to genetic liability (represented by schizophrenia patients, first-degree relatives, and controls) for the bilateral IFO, the left inferior longitudinal fasciculus (ILF), and the left tSLF. Diffusion tensor imaging studies have previously identified white matter abnormalities in all three of these tracts in schizophrenia; however, this study is the first to identify a significant genetic liability. Thus, FA of these three tracts may serve as biomarkers for studies seeking to identify how genes influence brain structure predisposing to schizophrenia. However, differences in FA and MD in frontal and temporal white matter pathways may be additionally driven by state variables that involve processes associated with the disease.

Figure 1. Regions of reduced fractional anisotropy (FA) suggest a genetic predisposition to schizophrenia

In all four of the tracts shown in the left-hand panel (left and right inferior fronto-occipital fasciculus; left inferior longitudinal fasciculus; and left temporal component of the superior longitudinal fasciculus (tSLF)), there were significant effects of both schizophrenia and genetic liability. Disease-related effects were only significant in the left tSLF. The graphs on the right-hand panel show the mean FA; error bars indicate standard error. See text and table 2 for full details.