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Six decades since Cade's six

Published online by Cambridge University Press:  24 June 2014

Gin S. Malhi*
Affiliation:
CADE Clinic, Discipline of Psychological Medicine, University of Sydney, Sydney, Australia. E-mail: gmalhi@med.usyd.edu.au
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Abstract

Type
Editorial
Copyright
Copyright © 2009 John Wiley & Sons A/S

The title of this editorial describes John Cade's contribution to neuropsychiatry as a ‘cricketing six’, and the question arises whether we have in any way bettered this score. Sixty years ago John Cade published his seminal paper in the Medical Journal of Australia Reference Cade(1). In this, he described the effects of lithium on a total of 10 patients. The patients are sometimes recounted as having bipolar disorder but in fact one was schizoaffective and, of the remaining nine, three had chronic mania whilst six had mania with an episodic pattern.

He had observed that lithium administration produced a profound effect on the mental state of these patients, usually within a matter of days, and that when lithium treatment was stopped these benefits were lost, but that the effect could be regained by reinstituting the medication. Indeed, affective symptoms improved in all the patients and the majority had a marked improvement in functioning. Cade deduced from this that lithium had a specific antimanic action and suggested that perhaps mania resulted from a ‘deficiency in the body of lithium ions‘.

Reading this today, in an era of randomised controlled trials and meta-analyses of clinical studies, it is difficult to comprehend how such a humble report achieved such significant impact. In reality lithium had a slow start and took some years to be tested further. Worldwide, its use as a potential treatment varied considerably and its uptake was resisted in the United States, for many years. However, with time lithium has ‘matured’ and gradually its richness is being fully realized. Indeed, lithium has been shown to be effective in treating many facets of mood disorders, both unipolar and bipolar, and is the only agent that is protective against suicide. Further, its neuroprotective properties hold much promise both for future treatments and for better understanding mood disorders. Therefore, to celebrate the achievements of lithium and the many that contributed to its discovery this issue is dedicated to research pertaining to bipolar disorder. Two wonderful reviews examine very different aspects of mood disorders specifically, nutrition, mood and behaviour and a model of bipolar disorder based on neuroimaging findings. Then a further two original articles report on studies conducted in bipolar patients using novel interventions.

Together these articles show the diversity and complexity of today's research into all facets of bipolar disorder and how our understanding of the illness is rapidly advancing. However, in practice we have yet to improve upon lithium and the many promising findings from basic science research await translation into clinical treatments.

References

Cade, JFJ.Lithium salts in the treatment of psychotic excitement. Med J Aust 1949;2:349352. Google ScholarPubMed