Ultrastructural Pathology of Oligodendrocytes and Myelinated Fibers in Prefrontal white Matter in Schizophrenia

In this chapter, we aimed to perform a qualitative and morphometric study of the ultrastructure of oligodendrocytes in BA 10 white matter (WM) in schizophrenia and in normal controls and to present ultrastructural alterations of myelinated fibers previously detected in BA 10 WM in schizophrenia compared to normal controls.

Electron microscopy and morphometry were used in the investigation. The size, volume density (Vv), and number (N) of oligodendrocyte organelles were measured in 21 patients with schizophrenia and 20 normal controls. The data were examined using the Kolmogorov–Smirnov test for normality. Pearson correlation analysis was used to look for probable relationships between the parameters measured and age, post-mortem interval, neuroleptic treatment, and disease duration.

In schizophrenia, we detected oligodendrocyte enlargement, vacuolation, a lack of ribosomes and mitochondria, and an accumulation of lipofuscin granules when compared to controls. Morphometry revealed a substantial decrease in Vv and N of mitochondria and an increase in Vv and N of lipofuscin granules and vacuoles in schizophrenia oligodendrocytes compared to controls. Abnormalities of myelinated fibers in WM in schizophrenia compared to normal controls included altered oligodendrocyte/axon interaction and myelin/axon integrity, axonal atrophy and degeneration of myelin sheaths and myelinated fibers.

Alterations of oligodendrocytes and myelinated fibers in schizophrenia provide evidence for the disturbance of their energy, lipid and protein metabolism in prefrontal WM. Abnormalities in oligodendrocytes and myelinated fibers might disturb axonal integrity and circuitry and contribute to the pathophysiology of schizophrenia.