Abnormal Cytoarchitecture

Investigations into the cellular organization or structure (cytoarchitecture) of the brain of schizophrenia patients have reported various abnormal arrangements of neurons in several structures, although some of these studies suffer from a lack of replicability. The pyramidal cells of the hippocampus, which normally lie in an orderly layer, have been found to be disoriented in some postmortem brains of patients with schizophrenia. Several studies have also reported cytoarchitectural disturbances in the entorhinal cortex of schizophrenia patients, including bizarre invaginations of the normally smooth surface, irregularities in the normal pattern of pre-alpha-cell clustering in layer 2, and misplacement of these layer 2 neurons into deeper cortical layers (Bunney et al., 1997; Arnold and Rioux, 2001).

There is also evidence for a mis-migration of neurons in the prefrontal, parietal, and temporal cortex (Bunney et al., 1997). During embryogenesis, cortical neurons are born in the ventricular zone and migrate to the cortical subplate, where they wait before migrating into the cortical plate to form the six layers of the cortex. This neuronal migration into the cortex is thought to be complete by the end of the second trimester in primates. With the use of several markers (MAP2, MAP5, SMI32), a number of studies found an abnormal density of cells in the subcortical white matter of postmortem schizophrenia patients. These cells are thought to be remnants of subplate neurons and therefore may indicate an incomplete migration of neurons into the cortex. Investigators also used NADPH-diaphorase as a marker of these subplate remnants. Normally, these neurons are found in high levels in the superficial white matter, with a smaller population found dispersed throughout the cortical layers. In postmortem studies of the prefrontal and temporal cortices, the majority of these neurons are found in the deeper white matter with very few located in the cortical mantle. This apparent "shift" in the distribution of this subpopulation of neurons is interpreted as representing an altered migration of neurons into the cortex. These findings are consistent with a neurodevelopmental disturbance occurring around the second trimester of gestation.

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