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deficiency-disease

John Cade

This article is about the Australian psychiatrist. For the leader of the Kent Rebellion, see Jack Cade. For the former Maryland State Senator, see John A. Cade

Dr John Frederick Joseph Cade AO (January 18, 1912-November 16, 1980) was an Australian psychiatrist credited with discovering (in 1948) the effects of lithium carbonate as a mood stabilizer in the treatment of bipolar disorder (then known as manic depression). In an age where the standard treatments for psychosis were electroconvulsive therapy and lobotomy, lithium had the distinction of being the first effective medication available to treat a mental illness.

Early career

Born in Murtoa, Victoria to a doctor, Dr. Cade was educated at the Scotch College and the University of Melbourne and worked at various mental asylums. Although trained as a psychiatrist, Dr. Cade served in the Australian Imperial Force as a surgeon during World War II. After Singapore fell into Japanese hands, he became a prisoner of war at Changi Prison where he spent three and a half years until the end of the war. During his imprisonment, he reportedly would observe some fellow inmates having strange, vascillating behaviour. He thought perhaps a toxin was affecting their brains and when it was eliminated through their urine, they lost their symptoms.

After the war, Dr. Cade served as the head of the Bundoora Repatriation Hospital in Melbourne. It was at an unused kitchen in Bundoora where he conducted crude experiments which led to the discovery of lithium as a treatment of bipolar disorder. These experiments mostly consisted in injecting urine from mentally ill patients into guinea pigs. These would appear to die faster than when healthy persons' urine was used, leading him to think that perhaps more uric acid was present in these samples. Then, in an effort to increase the water solubility of uric acid, he started to test lithium carbonate.

Cade's discovery of lithium carbonate's effect on mania

Cade was originally investigating the hypothesis that mania was related to urea and using lithium urate as part of an animal experiment (the lithium salt happened to be the most soluble of the simple urate salts). However, his use of careful controls in his experiments revealed that the lithium ion had a calming effect by itself. A small-scale trial on humans revealed that lithium had a powerful effect on mania in people. The calming effect was so robust that Cade speculated that bipolar disorder was a "lithium deficiency disease.

Early results were highly promising, but the toxicity of lithium led to several deaths of patients undergoing lithium treatment. Moreover, as a naturally-occurring chemical, lithium salt cannot be patented, meaning that its manufacturing and sales were not considered commercially viable. These factors prevented its widespread adoption in psychiatry for some years, particularly in the United States, where its use was banned until 1970.

One problem was that the difference between the sizes of ineffectual and toxic doses was very small and difficult to control. The control was later improved when suitable tests were developed to measure the lithium level in the blood.

John Cade, Royal Park and RANZCP

In 1952 Cade was appointed psychiatrist superintendent and dean of the clinical school at Royal Park Hospital. Two years later, at the request of the Mental Hygiene Authority which was planning to remodel Royal Park, he visited Britain for six months to inspect psychiatric institutions. On his return, he introduced modern facilities and replaced the rather authoritarian approach to patient care with a more personal and informal style that included group therapy. Concerned at the number of alcohol-related cases, he supported voluntary admission to aid early detection and later proposed the use of large doses of thiamin in the treatment of alcoholism.

He served as the federal president of the Royal Australian and New Zealand College of Psychiatrists in 1969-70, and also as the president for its Victoria branch from 1963 until his death in 1980. In the end, Dr. Cade's discovery did receive the widespread acknowledgements and praise it deserved. For his contribution to psychiatry, he was awarded a Kittay International Award in 1974 (with Mogens Schou from Denmark), and was made an Officer of the Order of Australia in 1976. Dr. Cade remained humble about his chance discovery, describing himself as merely a gold prospector who happened to find a nugget. Finally, in July of 2004, the Medical Journal of Australia reported that Cade's 1949 article, "Lithium salts in the treatment of psychotic excitement", was the number one most cited MJA article.

Troubled Minds

In 2004, Film Australia and SBS screened the documentary 'Troubled Minds - The Lithium Revolution', a 60 minute documentary portraying John Cade's discovery of the use of Lithium in mental illness. The documentary received international recognition winning the main prize at the International Vega Awards for Excellence in Scientific Broadcasting. Troubled Minds was also recognised locally with writer/director Dennis K. Smith winning the AWGIE Award for Best Documentary.

Quote

"I believe the brain, like any other organ, can get sick and it can also heal."

Neurochemistry of lithium carbonate

The biologically active element in lithium carbonate is the lithium cation, Li+. It is conjectured to act on over-active receptors in the cell membranes of neurons.

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