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This article is about the Australian psychiatrist. For the leader of the Kent Rebellion, see Jack 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.

Contents 1 Early career 2 Cade's discovery of lithium carbonate's effect on mania 3 Quote 4 Neurochemistry of lithium carbonate 5 References 6 See also 7 External links

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.

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.

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.

In the end, Dr. Cade's discovery did receive the widespread acknowledgements and praise it deserved. 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. 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.

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

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.

• Cade, JFJ; Lithium salts in the treatment of psychotic excitement. Med J Aust 1949, 36, p349-352

• Lithium pharmacology

• Another telling of the Cade story
• Toxicity profile of lithium carbonate
• Lithium Revisited, Can J Psychiatry 2001;46:322-327