Hypothesis that decreased glutamatergic signalling is involved in schizophrenia
The glutamate hypothesis of schizophrenia models the subset of pathologic mechanisms of schizophrenia linked to glutamatergic signaling. The hypothesis was initially based on a set of clinical, neuropathological, and, later, genetic findings pointing at a hypofunction of glutamatergic signaling via NMDA receptors. While thought to be more proximal to the root causes of schizophrenia, it does not negate the dopamine hypothesis, and the two may be ultimately brought together by circuit-based models.[1] The development of the hypothesis allowed for the integration of the GABAergic and oscillatory abnormalities into the converging disease model and made it possible to discover the causes of some disruptions.[2]
Like the dopamine hypothesis, the development of the glutamate hypothesis developed from the observed effects of mind-altering drugs. However, where dopamine agonists can mimic positive symptoms with significant risks to brain structures during and after use, NMDA antagonists mimic some positive and negative symptoms with less brain harm, when combined with a GABAA activating drug.[3][dubious – discuss] Likely, both dopaminergic and glutaminergic abnormalities are implicated in schizophrenia, from a profound alteration in the function of the chemical synapses, as well as electrical synaptic irregularities. These form a portion of the complex constellation of factors, neurochemically, psychologically, psychosocially, and structurally, which result in schizophrenia.
^Lisman JE, Coyle JT, Green RW, et al. (May 2008). "Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia". Trends in Neurosciences. 31 (5): 234–42. doi:10.1016/j.tins.2008.02.005. PMC 2680493. PMID 18395805.
^Behrens MM, Ali SS, Dao DN, et al. (December 2007). "Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase". Science. 318 (5856): 1645–7. Bibcode:2007Sci...318.1645B. doi:10.1126/science.1148045. PMID 18063801. S2CID 41932041.
^Nakao S, Nagata A, Masuzawa M, et al. (June 2003). "NMDA receptor antagonist neurotoxicity and psychotomimetic activity". The Japanese Journal of Anesthesiology. 52 (6): 594–602. PMID 12854473.
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dopamine hypothesisofschizophrenia or the dopamine hypothesisof psychosis is a model that attributes the positive symptoms ofschizophrenia to a disturbed...
also be responsible for deficits in working memory. The glutamatehypothesisofschizophrenia links alterations between glutamatergic neurotransmission...
understood. A number of hypotheses including the dopamine hypothesis, and the glutamatehypothesis have been put forward in an attempt to explain the link...
schizophrenia. They claim these results are consistent with the glutamatehypothesisofschizophrenia, which proposes that dysfunction in this neurotransmitter...
further brain development, glutamate receptors broke down. This theory supports the glutamatehypothesisofschizophrenia. Another study in 2009 by Simon...
aging. Schizophrenia may also have to do with irregular NMDA receptor function (the glutamatehypothesisofschizophrenia). Increased levels of another...
onset of catatonia can be acute or subtle and symptoms can wax, wane, or change during episodes. It has historically been related to schizophrenia (catatonic...
The most commonly supported theories are the dopamine hypothesis and the glutamatehypothesis. Multiple genetic and environment factors have been associated...
varying levels of gliotransmission and calcium excitability. One theory, called the glutamatehypothesisofschizophrenia, suggests that glutamate deficiency...
dopamine activity and NMDArs, thus linking dopamine hypothesisofschizophrenia with the glutamatehypothesisof the disease. Kynurenic acid is reduced in individuals...
Evidence for the involvement ofglutamate in schizophrenia includes analogous symptoms which are produced by glutamate NMDA receptor antagonists such...
Javitt D (January 2012). "From revolution to evolution: the glutamatehypothesisofschizophrenia and its implication for treatment". Neuropsychopharmacology...
2018). "Beyond the dopamine hypothesisofschizophrenia to three neural networks of psychosis: dopamine, serotonin, and glutamate". CNS Spectrums. 23 (3):...
received regulatory approval (e.g. by the FDA of the US, the TGA of Australia, the MHRA of the UK) for schizophrenia, bipolar disorder, irritability in autism...
antipsychotic) to be discovered. It is primarily used to treat people with schizophrenia and schizoaffective disorder who have had an inadequate response to...
a glutamate–glutamine cycle, which results in reuptake ofglutamate from the synapse into the pre-synaptic cell to be recycled, keeping glutamate from...
expression of GAD-67 enzyme, which catalyses the transition ofglutamate to GABA. Blood levels of reelin and its isoforms are also altered in schizophrenia, along...
basis of hallucinations has been explored on the cellular receptor level. The glutamatehypothesis, proposed as a possible cause for schizophrenia, may...
mimic schizophrenia. In contrast to schizophrenia, LSD can induce transcendent experiences, or mental states that transcend the experience of everyday...
protein GAD67, an enzyme that catalyzes the formation of GABA from glutamate. Individuals with schizophrenia have shown a decrease in GAD67 levels and this deficit...
"Progress towards validating the NMDA receptor hypofunction hypothesisofschizophrenia". Current Topics in Medicinal Chemistry. 6 (8): 771–85. doi:10...
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