Schizophrenia is believed to result from altered neuronal connectivity and impaired myelination. However, there are few direct evidence for myelin abnormalities in schizophrenia. We performed electron microscopic study of myelinated fibers and oligodendrocytes and morphometric study of myelinated fibers in the prefrontal cortex in gray and white matters in schizophrenia and normal controls. Six types of abnormal fibers and ultrastructural alterations of oligodendrocytes were found in schizophrenia. No significant group differences in area density of myelinated fibers were found. Frequency of pathological fibers was increased significantly in gray matter in young and elderly schizophrenia patients and in patients with predominantly positive symptoms. In contrast, in white matter, frequency of altered fibers was increased significantly in elderly patients, in patients with predominantly negative symptoms, and correlated with illness duration. Progressive alterations of myelinated fibers in white matter might be followed by alterations of myelinated fibers in gray matter in schizophrenia. 1. Introduction Growing evidence coming from neuroimaging and postmortem studies support the notion that altered neuronal connectivity in schizophrenia is associated with disturbed myelination in different fiber tracts [1–9]. Abnormalities of oligodendrocytes in gray and white matters in schizophrenia are among the most consistent findings. Myelin and oligodendrocyte abnormalities have been reported in schizophrenia in neuroimaging, neurocytochemical, microarray, and morphometric studies [1]. In vivo neuroimaging studies demonstrated reduced white matter volume in the prefrontal cortex [10]. Buchsbaum et al., [11] in PET study, found an increased relative metabolic rates in white matter in schizophrenia. Metabolic abnormalities in fronto-striatal-thalamic white matter tracts have been reported in schizophrenia [12]. MR diffusion tensor imaging (DTI) can measure and visualize organization of white matter fiber tracts in vivo. DTI studies of white matter in schizophrenia demonstrated a significant reduction in fractional anisotropy (FA) in frontal lobe and the relationships between white matter abnormalities and symptoms of the disorder [13–16]. It is not known whether the abnormalities observed to date reflect a decrease in number of axons, decreased axonal diameter, thinner myelin sheaths, or less coherent fibers. Morphometric studies revealed prominent deficit of oligodendrocytes in different brain regions, including gray and white matter of the prefrontal cortex in
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