Abstract
Introduction:Diffusion tensor imaging has revealed differences in all examined white matter tracts in schizophrenia, with a range of explanations for why this may be. The distribution and timing of differences may help explain their origin; however, results are usually dependent on the analytical method. We therefore sought to examine the extent of differences and their relationship with age using two different methods.Methods:A combined voxel-based whole-brain study and a tract-based spatial-statistics study of 104 patients with schizophrenia and 200 matched healthy controls, aged between 17 and 63 years.Results:Fractional anisotropy was reduced throughout the brain in both analyses. The relationship of fractional anisotropy with age differed between patients and controls, with controls showing the gentle fractional anisotropy decline widely noted but patients showing an essentially flat relationship: younger patients had lower fractional anisotropy than controls, but the difference disappeared with age. Mean diffusivity was widely increased in patients.Conclusion:Reduction in fractional anisotropy and increase in mean diffusivity would be consistent with global disruption in myelination; the relationship with age would suggest this is present already at the onset of their illness, but does not progress.
Highlights
Diffusion tensor imaging has revealed differences in all examined white matter tracts in schizophrenia, with a range of explanations for why this may be
Schizophrenia is increasingly recognised as a disorder of connectivity (Fornito et al, 2012; Friston, 2002; Stephan et al, 2006), with the structural basis of that disconnection in white matter commonly examined with Diffusion Tensor Magnetic Resonance Imaging (DTI) (Basser et al, 1994)
These measures have been extensively applied to schizophrenia datasets and have almost invariably shown patients to be different to healthy controls (Kanaan et al, 2005), with their fractional anisotropy (FA) usually lower and their mean diffusivity (MD) usually higher, suggesting some disruption to the normal white matter architecture
Summary
Diffusion tensor imaging has revealed differences in all examined white matter tracts in schizophrenia, with a range of explanations for why this may be. MD measures the extent to which water is able to diffuse in any direction (so is high in areas such as the cerebro-spinal fluid, where its motion is relatively unconstrained), whereas FA measures what proportion of that diffusion is constrained (so is high in areas such as white matter, where myelinated axonal walls mean water can diffuse along, but not across, cells) These measures have been extensively applied to schizophrenia datasets and have almost invariably shown patients to be different to healthy controls (Kanaan et al, 2005), with their FA usually lower and their MD usually higher, suggesting some disruption to the normal white matter architecture. Functional interpretations are common, with symptoms seen as manifested by differences in specific tracts and
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