Glutamate hypothesis of schizophrenia

Glutamate hypothesis of schizophrenia

The glutamate hypothesis of schizophrenia models the subset of pathologic mechanisms 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. cite journal |author=Lisman JE, Coyle JT, Green RW, "et al" |title=Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia |journal=Trends Neurosci. |volume=31 |issue=5 |pages=234–42 |year=2008 |month=May |pmid=18395805 |doi=10.1016/j.tins.2008.02.005 |url=http://linkinghub.elsevier.com/retrieve/pii/S0166-2236(08)00089-1] 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. cite journal |author=Behrens MM, Ali SS, Dao DN, "et al" |title=Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase |journal=Science (journal) |volume=318 |issue=5856 |pages=1645–7 |year=2007 |month=December |pmid=18063801 |doi=10.1126/science.1148045 |url=http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=18063801]

Unlike dopamine hypothesis, the development of which began with serendipitously discovered molecule able to stop psychosis, the glutamate hypothesis started off when a pathological action of a street drug was described that mimicked the less vivid but more pervasive symptoms of schizophrenia. And, unlike the prior, this hypothesis has led to a development of an antipsychotic prototype on scientific grounds. It may possibly bring the medications targeting glutamate receptors and offering a safer, more tolerable, and more effective treatment.

Current State of Schizophrenia Treatment

Schizophrenia is now treated by medications known as antipsychotics (or neuroleptics) that block dopamine receptors or reduce excess quantities of dopamine in the brain; unfortunately, these drugs are well known to have unpleasant side effects that often interfere with recovery, rehabilitation, and relapse prevention. These side effects can interfere so greatly with the life of patients, or are so disliked, that patients cease to take their medications of their own accord--and these medications can be the only things standing between them and the active psychosis of schizophrenia.

The more common side effects from currently used antipsychotics include general sedation, emotional numbness, apathy towards life and activities (the "Thorazine shuffle"), rapid weight gain, leading to obesity, and possible induction of diabetes. There are also several relatively uncommon, but extremely severe reactions that a person taking these medications may suffer, including tardive dyskinesia for the older typical antipsychotics, neuroleptic malignant syndrome for the newer atypical antipsychotics, and potentially lethal agranulocytosis for clozapine, the most effective antipsychotic. In addition, antipsychotic treatment does not generally restore full pre-onset functioning.

However, antipsychotics are the only 'proven' treatment for schizophrenia and even with all the side effects of antipsychotics, this treatment is arguably not worse than the disease. (See dopamine hypothesis of schizophrenia for more on current treatments for schizophrenia.)

Possible glutamate based treatment

It has been reported in the New York Times that a new drug [ [http://www.nytimes.com/2008/02/24/business/24drug.html Daring to Think Differently About Schizophrenia - New York Times ] ] in clinical trials (known as LY2140023, being developed by Eli Lilly & Company) shows a potential for the treatment of schizophrenia; this new drug affects certain glutamate receptors in the brain, known as NMDA receptors. [ [http://news.bbc.co.uk/2/hi/health/6971037.stm BBC NEWS | Health | Schizophrenia trials 'promising' ] ]

Notes and references

ee also

*Schizophrenia
*Antipsychotic
*Dopamine hypothesis of schizophrenia
*Glutamate
*Typical antipsychotic
*Atypical antipsychotic

External links

* [http://www.schizophreniaforum.org/for/curr/Moghaddam/default.asp Glutamate Hypothesis of Schizophrenia] By Bita Moghaddam


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