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"Chemical Imbalance"
Professor C Heather Ashton DM, FRCP
August 28, 2001

School of Neurosciences
Division of Psychiatry
The Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne NE1 4LP

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Question posed by Barry Haslam: "Is mental illness caused by an imbalance of chemicals in the brain... ?"

Answer by Professor Heather Ashton: You ask what seems to be a simple question, but I am afraid the answer is far from simple. The idea that mental illness is caused by an imbalance of chemicals in the brain started in the 1950s when nearly all the currently used psychiatric drugs were discovered by chance to alleviate the symptoms of certain mental illnesses. For example, the monoamine oxidase inhibitors (MAOIs) were originally developed as a cure for tuberculosis, but it was found that patients with advanced TB became unusually happy when taking them, and this led to their use as antidepressants - e.g. phenelzine. The neuroleptics were originally introduced as antihistamines but it was found serendipitously that they alleviated some of the symptoms of schizophrenia which led to their use in that condition - e.g. chlorpromazine. The tricyclic antidepressants have a similar structure to chlorpromazine and were first tried in schizophrenic patients. It was noticed (by nurses) that those with depression became less depressed and this led to trials in patients with depression. Benzodiazepines were also discovered by chance when it was found that they calmed down aggressive and frightened experimental animals - and stopped Siamese fighting fish from fighting. They were then tried in humans and found to have dramatic effects in alleviating panic attacks (in very large doses), and their use then enlarged to include all forms of anxiety.

Many of the early trials of all these drugs were financed by the drug companies whose chemists had developed these drugs and were looking for a market. The drugs were mostly initially tried in hospitals in Europe which had chronic patients, usually with schizophrenia or TB. However, the psychiatrists quickly embraced the idea that if chemicals could help mental conditions, then the conditions must be caused by chemical imbalances.

This idea stimulated further research (largely by drug companies) to find out the actions of the drugs. Neuroleptics were found to block dopamine receptors and from that grew the dopamine theory of schizophrenia. Antidepressants were found to increase monoamines, including serotonin, and from that grew the serotonin theory of depression. Benzodiazepines were, later, found to bind to GABA receptors (like barbiturates) and that engendered a spate of similar drugs which were used in all anxiety conditions (which are very common).

While drug companies certainly encouraged the idea that mental illnesses are caused by imbalance of brain chemicals (and even "invented" illnesses to go with the drugs - see accompanying book review), psychiatrists quickly lapped up the idea because it gave them an easy (and better at the time) form of treatment. Also it started a sort of revolution in scientific thought because for the first time symptoms that were thought of as merely "psychological" appeared to have a real physical/chemical basis; this provoked much further research into the way the brain works.

There is probably a grain of truth in this idea, although it is now clear that it is a gross oversimplification. You just cannot just say schizophrenia = dopamine imbalance; depression = serotonin imbalance; anxiety = GABA imbalance, etc. However, it is now recognised that the brain works on a physicochemical basis and that every symptom has a real cause which probably involves complicated interactions between a large number of neurotransmitters. Whether psychiatric or psychological symptoms can be cured by drugs is of course another matter. Furthermore, when the drugs were introduced nobody thought of long-term effects, dependence or withdrawal reactions! We still don't know the answers, but we have to admit that some drugs have helped some people (sometimes dramatically) and that they have increased understanding of brain functions. It is clear that drugs have to be used judiciously with awareness of their adverse effects and hope that things will improve as understanding grows. Whether drugs will ever "cure" mental illnesses remains a matter for doubt.

I enclose a book review about psychopharmacology which I wrote by request for the British Journal of Psychiatry. This covers some other facets of your question, and you will see that I am as troubled about the influence of the drug companies as you are.

Congratulations on your recent award as campaigner of the year.

Best wishes,


C.H. Ashton
Professor Ashton's Main Page

• See also: Brainwashed: Mental illnesses are caused by chemical imbalances in the brain, right? Wrong, says Craig Newnes, The Guardian, January 10, 2002

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