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.
Neuroimaging and microarray studies provide evidence for myelin and oligodendrocyte abnormalities in schizophrenia (SZ). Electron microscopy demonstrated dystrophy, necrosis and apoptosis of oligodendrocytes, the most severely affected cells in SZ. The proportion of myelinated fibres with atrophy of axon and swelling of periaxonal oligodendrocyte processes increased significantly in the prefrontal cortex (PFC), caudate nucleus and hippocampus in SZ compared to controls. Morphometry showed a deficit of oligodendrocytes in the PFC and in adjacent white matter, lower number of oligodendroglial satellites of pyramidal neurons and a loss of pericapillar oligodendrocytes in the PFC in SZ compared to normal controls. A lowered number of oligodendrocytes in the PFC was also found in mood disorders. These data provide evidence for altered oligodendrocyte-axon, oligodendrocyte-neuron and oligodendrocyte-capillar interactions in SZ brains suggesting a key role of damage and loss of oligodendrocytes in altered neuronal connectivity and in atrophy of neurons in SZ.
Ultrastructural abnormalities of capillaries and of pericapillary cellular environment found suggest that blood-brain barrier dysfunction might contribute to the pathogenesis of cortical lesions in schizophrenia.
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