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.
Neuroimaging studies have shown that the core symptoms of schizophrenia are associated with local changes of cerebral blood flow, particularly in the frontal cortex. Previously we reported ultrastructural damage of capillaries in the upper layers of the prefrontal cortex, Brodmann's area (BA) 10 and in the visual cortex, BA 17 in schizophrenia. An electron microscopic morphometric study was performed to estimate capillary area density (N cap/mm 2 ) in two upper layers of the prefrontal and visual cortices in 26 cases of schizophrenia and 26 normal controls. Capillary area density was lower in the prefrontal cortex in the schizophrenia group (-24%, p < 0.001) and in the subgroup of schizophrenia with predominantly negative symptoms (n=12, -35%, p < 0.001) as compared to controls. Group and subgroup differences were absent in the visual cortex. Dysfunction of neocortical microvasculature in schizophrenia is related to region-specific capillary deficiency in the prefrontal cortex. These changes might contribute to the lowered blood flow, reduced glucose metabolic rates, resting hypofrontality and hypoactivation reported in the prefrontal cortex of patients with schizophrenia.
MF pathology is similar in attack-like and continuous paranoid schizophrenia but differ by the degree of severity of pathological MF. Abnormalities in MF contribute to the disconnectivity between the prefrontal cortex, caudate nucleus and hippocampus.
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