Glutamate theories of schizophrenia were first proposed over 30 years ago and since that time have become increasingly accepted. Theories are supported by the ability of N-methyl-D-aspartate receptor (NMDAR) antagonists such as phencyclidine (PCP) or ketamine to induce symptoms that closely resemble those of schizophrenia. Moreover, NMDAR antagonists uniquely reproduce the level of negative symptoms and cognitive deficits observed in schizophrenia, suggesting that such models may be particularly appropriate to poor outcome forms of the disorder. As opposed to dopamine, which is most prominent within frontostriatal brain regions, glutamate neurons are present throughout cortex and subcortical structures. Thus, NMDAR theories predict widespread disturbances across cortical and thalamic pathways, including sensory brain regions. In auditory cortex, NMDAR play a critical role in the generation of mismatch negativity (MMN), which may therefore serve as a translational marker of NMDAR dysfunction across species. In the visual system, NMDAR play a critical role in function of the magnocellular visual system. Deficits in both auditory and visual processing contribute to social and communication deficits, which, in turn, lead to poor functional outcome. By contrast, NMDAR dysfunction within the frontohippocampal system may contribute to well described deficits in working memory, executive processing and long-term memory formation. Deficits in NMDAR function may be driven by disturbances in presynaptic glutamate release, impaired metabolism of NMDAR modulators such as glycine or D-serine, or intrinsic abnormalities in NMDAR themselves.
A study of the degree of inflammatory response of atherosclerotic plaque in the coronary artery in patients with impaired metabolism of homocysteine and vitamin D
