Brain biochemistry

Disturbance of the 'chemical balance' in the brain is frequently suggested as part of the background to mental illness. In the case of schizophrenia, the introduction of effective antipsychotic drugs in the 1960s, starting with chlorpromazine, gave rise to neurochemical theories of causation. When the drugs were introduced, they were dramatically effective, and allowed many long-term hospital inpatients to be discharged. They were known to be effective antihistamine drugs, but the previous generation of antihistamines did not have their powerful antipsychotic properties.

Studies were therefore done to see how these new drugs worked. It was found that they were probably working by action on the substance dopamine, which is a naturally occurring neurotransmitter in the brain. (A neurotransmitter is a chemical messenger that is released in small packets at the surface of one nerve cell - the synapse - allowing it to communicate with its neighbouring nerve cells by interaction with receptors on it.) For example, the potency of a drug per milligram, in blocking dopamine, was directly in proportion to its potency as an antipsychotic in clinical practice.

In line with this theory of how they work was the observed side-effect of antipsychotic drugs to produce stiffness and shakiness of the muscles, as in Parkinson's disease, which is itself known to be caused by a lack of dopamine in certain parts of the brain (the substantia nigra of the basal ganglia).

Other evidence supporting a role for dopamine includes the fact that drugs, such as amphetamines, which stimulate dopamine, can precipitate a schizophrenia-like condition (amphetamine psychosis). This point is somewhat vitiated, however, by the fact that such conditions can also be produced by other illicit drugs, including cannabis and LSD, which affect different neurotransmitter systems.

Some studies have shown changes in the number of dopamine receptors in the brains of patients with schizophrenia after death, but these are difficult to interpret because most of the patients will have received antipsychotic drugs, and it is not possible to be absolutely sure that the changes in dopamine receptors are not due to the effects of the drugs.

The subtype of D2 dopamine receptors has been particularly closely studied. Unfortunately, as with genetics, the continuation of research has caused simplistic theories of 'excessive D2 function = schizophrenia' to have to be abandoned. For example, clozapine is an extremely potent antipsychotic drug, but it has only weak D2 effects; this agent is powerful at 5HT2a receptors.

Other neurotransmitters, such as GABA, ACh, serotonin, and glutamate, have also been implicated. It seems clear that dopamine is concerned in the process, but also that this is not the whole story.

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