Compromised White Matter Tract Integrity in Schizophrenia Inferred From Diffusion Tensor Imaging

Abstract

THERE IS now little controversy regarding the claim that the brains of patients with schizophrenia are structurally and functionally compromised. Abnormalities occur in both gray matter and white matter. In vivo magnetic resonance imaging studies report volume deficits more often in cortical gray than white matter^1-4 and are consistent with neuropathologic observations of increased neuronal density and decreased neuropil⁵ presence of smaller neurons in layer III of the prefrontal cortex and absence of glial cell enlargement.⁶ There have also been reports of reduced prefrontal lobe white matter volume in patients with schizophrenia^7,8 and of patchy signal intensity differences between patients with schizophrenia and controls that affect white matter tracts.⁹ Proton magnetic resonance spectroscopic imaging, which provides in vivo indices of some brain metabolites, has shown abnormally low white but not gray matter signals of N-acetyl (NAc) compounds, primarily N-acetyl aspartate, a putative marker for living mature neurons, in patients with schizophrenia who had abnormally small gray but not white matter volumes.¹⁰ The low white matter NAc signal was interpreted as potentially reflecting compromised neuronal connectivity.^11-14 Evidence from postmortem studies supports the in vivo findings of anomalous white matter in schizophrenia, including selective displacement of interstitial white matter neurons in the prefrontal and temporal¹⁵ cortex and delayed myelination in frontal white matter.^16,17 These neuropathologic signs may be reflected in measurements sensitive to directional coherence or connectivity of fiber tracts.