Schizophrenia glutamate hypothesis

Glutamatergic abnormalities are also a major feature of schizophrenia. They may actually cause the dopaminergic abnormalities in that disorder and then be exacerbated by them (Laruelle et al., 2005). The glutamate hypothesis simply states that NMDAR hypofunction contributes to the pathophysiology of schizophrenia (Coyle, 2006 Lindsley et al., 2006). A variant of this is the NMDA synaptic deficit hypothesis of MacDonald and Chafee (2006), which posits that each risk factor for schizophrenia impacts the NMDA glutamate synapse such that the cumulative effect drives NMDA synaptic function below a threshold for normal function. Supporting either form of the glutamate hypothesis is evidence that... 

One of the most popular hypotheses to explain schizophrenia, the glutamate hypothesis of schizophrenia, is based on the observation of psychotomimetic effects of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine (PCP), dizocilpine (MK-801), and ketamine. Like amphetamine, NMDA antagonists produce a psychosis-like state when administered to healthy individuals. Further... 

Coyle JT Glutamate and schizophrenia Beyond the dopamine hypothesis. Cell Mol Neurobiol 2006 26 365. [PMID 16773445]... 

It may be concluded that despite the importance of the dopamine hypothesis of schizophrenia in serving to unify the mechanism of action of both typical and atypical neuroleptics, it is apparent that some serotonin receptor subtypes, and glutamate receptors of the NMDA subtype, may also play a crucial role. 

The glutamate hypofunction hypothesis relies on the fact that phencyclidine and ketamine, both potent noncompetitive N-methyl-D-aspartate (NMDA)-glutamate receptor antagonists, induce schizophrenia-like symptoms in healthy individuals and worsen some symptoms in schizophrenia patients... 

Kim JS, Komhuber HH, Schmid-Burgk W, Holzmuller B. 1980. Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis of schizophrenia. Neurosci Lett 20 379-382. 

Biological Role of Glutamate and the NMDA Receptor Hypofunction Hypothesis of Schizophrenia... 

As described in the previous sections, neuropathological studies demonstrated alterations in the levels of several synaptic proteins in the PFC, hippocampus, and cerebellum of patients with schizophrenia (13, 15, 53). These observations have lead to the hypothesis that the clinical symptoms of schizophrenia are manifestations of abnormal neural circuitry and dysfunctional communication between different brain regions (22, 51). These abnormalities affect multiple neurotransmitter systems. Although dopamine dysfunction in schizophrenia is widely accepted, a growing body of evidence suggests the involvement of glutamate, GABA, and other neurotransmitters in schizophrenia. 

Coyle JT. Glutamate and schizophrenia beyond the dopamine hypothesis. Cell. Mol. Neurobiol. 2006. 

Keywords Schizophrenia Major depression Thl/Th2 balance Pro-inflammatory cytokines NMDA hypothesis Glutamate Serotonin Tryptophan Kynurenine Kynurenic acid HPA axis... 

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