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Neurotransmitter Systems Associated with Schizophrenia

Dopamine in Schizophrenia

The Typical Antipsychotics, which were the first class of medications discovered that were able to treat at least the positive symptoms of Schizophrenia, work by blocking the D2 dopamine receptors in the brain. In fact, blocking 60-80% of the D2 receptors will allow psychotic symptoms to subside; blocking these receptors by more than this amount will cause extrapyramidal symtpoms to occur.

Based on these facts, as well as the finding that stimulating the D2 receptors can trigger psychotic symptoms in an individual, it became clear that dopamine functioning is responsible at least in part for the positive symptoms of Schizophrenia.

There is some recent evidence that in Schizophrenia, the main problem with dopamine functioning has to do with abnormalities of presynaptic dopamine synthesis and/or release [ref].

Other neurotransmitters in Schizophrenia

Clozapine, which is the most effective medication available for treating the symptoms of Schizophrenia, is a very weak blocker of the D2 dopamine receptors. This suggests that there must be other neurotransmitter systems that are also involved in causing Schizophrenia, though so far not much is known about what are these other factors.

One neurotransmitter that has gotten increased attention in recent years for its role in Schizophrenia in glutamate, which targets NMDA receptors in the brain. Phencyclidine (PCP) and Ketamine are two drugs that block the actions of glutamate at the NMDA receptor, and these drugs can cause both the positive and negative symptoms of Schizophrenia in people who do not have the condition.   Increasing the actions of glutamate by using high doses of precursor molecules that are metabolized into glutamate, such as D-serine, glycine and D-cycloserine, show promise in helping to improve the negative symptoms of Schizophrenia

[ref, ref]

Brain Regions

Congenital Factors