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David Baxter

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Drug-Induced Psychosis Indistinguishable from Schizophrenia
July 24, 2007

A new study by scientists at University of California, MIND Institute covers interesting results related to epilepsy and psychosis based on the glutamate hypothesis.

Although the dopamine hypothesis is possibly the most commonly known neurotransmitter theory for schizophrenia, there is also overwhelming evidence that Glutamate plays a part in the disorder. Glutamate's receptor, N-methyl-d-aspartate (NMDA), is believed to have reduced function, or be ?inhibited? in schizophrenia. Much of the support for this theory comes from the reaction many individuals have to drugs that block glutamate at the NMDA receptor. Some of these "street" drugs are pencyclidine (PCP), and Ketamine (Special K).

The researchers found that "The psychosis produced by these drugs is indistinguishable from schizophrenia and includes both positive and negative symptoms."​
This is important information in future prevention because these drug-induced psychoses may account for many of the cases of schizophrenia. There is a lot of research showing drug use can increase risk for development of schizophrenia (see latest news in drugs and schizophrenia), but this provides a clear connection that these drugs produce psychosis indistinguishable from schizophrenia.

The researchers focused on the drug-induced psychosis that occurs after puberty using rats as a way to test their theories. Rats and mice are frequently used in this type of research because they share approximately 99% of the genes that humans have (so the research is usually representative of the types of results that they would expect to see in humans), and because such testing could never be done on humans due to ethical reasons. The rats were administered the drugs (PCP) that block the NMDA Glutamate receptor to induce psychosis.

The researchers argue, "this psychosis is an atypical form of limbic epilepsy. Moreover, there is a specific limbic thalamcortical (connecting of the cortex and the thalamus) psychosis circuit that mediates cell injury in limbic cortex of rodents and may mediate this PCP-induced psychosis in humans. It is proposed that this thalamocortical psychosis circuit develops at puberty and can mediate PCP and ketamine-mediated psychosis and possibly the psychosis of schizophrenia, bipolar disease and other disorders that have their onset at puberty," wrote F.R. Sharp and colleagues, University of California, MIND Institute.
The researchers concluded: "Finally, based on this developmentally regulated psychosis/epilepsy-related thalamocortical circuitry, it is proposed that antiepileptic drugs that promote GABAergic mechanisms may decrease the probability of episodic psychosis from any cause."​
The connection of psychosis to epilepsy is interesting because it may provide new pathways for treatment. Prescribing antiepileptic/anticonvulsant medications is already common practice when treating treatment resistant schizophrenia. These medications have been shown in some people to decrease irritability, positive symptoms, and anxiety or aggressive behaviors. Lamotrigine (Lamictal), is an anticonvulsant medication that acts on glutamate and has recently been shown to be beneficial in some patients with schizophrenia. Commonly it is augmented with an antipsychotic, usually Clozaril.

Full Press Release: Scientists at University of California, MIND Institute detail research in psychosis.

Research Article: Sharp FR, Hendren RL.(2007). Psychosis: atypical limbic epilepsy versus limbic hyperexcitability with onset at puberty? Epilepsy Behav.;10(4):515-20.
 

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