Differential susceptibility of white matter tracts to inflammatory mediators in schizophrenia: An integrated DTI study

Abstract

BackgroundThe pathophysiological underpinnings of impaired anatomical and functional connectivity are not precisely known. Emerging data suggest that immune mediators may underlie such dysconnectivity. We examined anatomical brain connections using diffusion tensor imaging (DTI) data in relation to interleukin-6 (IL-6) and C-reactive protein (CRP) levels among early-course clinically stable schizophrenia subjects compared to healthy controls (HC). MethodsDTI data were acquired in 30 directions with 2 averages. Fractional anisotropy (FA) and radial diffusivity (RD) maps were separately processed using FSL4.1.9 and Tract-Based Spatial Statistics (TBSS). Threshold free cluster enhancements (TFCE) were examined employing familywise error (FWE) corrections for multiple testing within linear regression models including age, sex and socioeconomic status as covariates. IL-6 and CRP were assayed using highly sensitive and specific sandwich immunosorbent assays. ResultsThe groups did not differ in age and sex as well as in the IL-6 and CRP levels. IL-6 levels were negatively correlated with the FA and positively correlated with RD among schizophrenia subjects but not HC. The voxel clusters that showed significant correlations were localized to the forceps major, the inferior longitudinal fasciculus and the inferior fronto-occipital fasciculus. CRP levels showed similar pattern except for lack of correlation with RD on any cluster that corresponded to the forceps major. DiscussionOur results suggest that the IL-6 and CRP contribute to impaired anisotropy of water diffusion in selected pathways that have been previously associated with schizophrenia suggesting differential susceptibility of selected neural pathways to immune mediators.