Diffuse abnormality of low to moderately organized white matter in schizophrenia

Increasing evidence suggests that abnormal white matter is central to the pathophysiology and, potentially, the pathogenesis of schizophrenia (SCZ). The spatial distribution of observed abnormalities and the type of white matter involved remain to be elucidated. Seventeen chronically ill individuals with SCZ and 17 age- and gender-matched controls were studied using a 3T magnetic resonance imaging diffusion tensor imaging protocol designed to examine the abnormalities of white matter by region and by level of architectural infrastructure as assessed by fractional anisotropy (FA) in native space. After assessing whole-brain FA, FA was divided into quartiles, capturing all brain regions with FA values from 0 to 0.25, 0.25 to 0.5, 0.5 to 0.75, and 0.75 to 1.0. Mean whole-brain FA was 4.6% smaller in the SCZ group than in healthy controls. This difference was largely accounted for by FA values from the second quartile (between 0.25 and 0.5). Second quartile FA was decreased in all 130 brain regions of the template in the SCZ group, with the difference reaching statistical significance in 41 regions. Correspondingly, the amount of brain tissue with an FA of ∼0.4 was significantly reduced in the SCZ group, while the amount of brain tissue falling in the lowest quartile of FA was increased. These findings strongly imply a diffuse loss of white matter integrity in SCZ. Our finding that the loss of integrity disproportionately involves white matter of low to moderate organization suggests an approach to the specificity of white matter abnormalities in SCZ based on microstructure rather than spatial distribution.