The neuropathological basis of schizophrenia has remained elusive for over a hundred years, but several issues are now becoming clear. The brain is slightly smaller, and there are quantitative alterations in the size, density, and synaptic connections of neurons in several brain areas, especially the hippocampus, frontal cortex, and thalamus. The oligodendrocyte class of glia is also implicated. There is no evidence of Alzheimer's disease pathology nor any other neurodegenerative disease processes. The observations are consistent with a subtle change in the synaptic organization of the brain in schizophrenia. It is likely that this contributes to the aberrant functional connectivity between brain regions which is thought to underlie the cardinal features of the syndrome. Synapses using glutamate acting via the NMDA receptor may be involved. The neuropathology likely begins in early development and to affect brain plasticity throughout life. It is proposed to be a manifestation of the susceptibility genes for schizophrenia identified recently. © 2005 Elsevier Ltd. All rights reserved.
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