Under the Microscope:Bipolar disorder, also known as manic depression, is a severe psychiatric disorder. It is characterised by alternate periods of euphoria and deep depression, writes Dr William Reville
For half a century now the symptoms of this disorder have been successfully treated by lithium salts. New findings now indicate that lithium salts may also be used to treat various neurological ailments including Alzheimer's disease, Huntington's disease, the psychotic disorder of schizophrenia and to reduce the effects of stroke. Expanded details are described by Jochen Paulus in Scientific American Mind (April/May 2007).
Bipolar disorder is largely an inherited condition. A child who has one parent afflicted with the disorder has a 27 per cent chance of being affected. If both parents have bipolar disorder the child has a 50-75 per cent chance of inheriting the condition. About 70 per cent of cases of bipolar disorder begin after the age of 20. According to Paulus, 2 to 3 per cent of Americans suffer from bipolar disorder. This to me is a surprisingly high figure and leads me to wonder if the condition is being over-diagnosed. Tragically up to 15 per cent of sufferers eventually die by suicide, although Paulus reports that recent studies indicate that lithium treatment may prevent up to 60 per cent of these deaths.
There are side-effects of lithium treatment and levels of lithium in blood must be monitored regularly to ensure that the proper concentration is maintained. Common side-effects include: blurred vision, dry mouth, fine hand tremor, frequent urination and mild nausea. Long-term effects include weight gain, possible hypothyroidism and kidney dysfunction. People with kidney disease should not take lithium.
Lithium is the lightest of a group of elements in the atomic table of elements known as the alkali metals. For medicinal purposes it is administered to the patient in the form of a water-soluble salt of the metal, eg lithium carbonate, lithium sulphate or lithium citrate. In the body these salts break down into positively charged lithium atoms (ions) and negatively charged salt elements. The lithium ion is thought to be the active ingredient.
An Australian psychiatrist John Cade discovered lithium's power as a psychoactive drug in the 1940s, noting that the salt lithium urate had a calming effect on manic patients. This work was confirmed and extended in the 1950s. Fears of toxic side-effects slowed the acceptance of lithium, so it was not approved as a medication in the US until 1970.
Much research as been carried out since the 1970s to elucidate the mechanism of lithium's effect on the brain. In summary it appears that, in addition to altering chemical messenger molecules (neurotransmitter) levels, lithium may act to boost the number of nerve cells (neurons) in the brain. Patients with bipolar disorder have relatively less grey matter in their brains compared with those without the disorder. The grey matter in brain consists mainly of nerve cell bodies and the paucity of grey matter in bipolar brains is either because nerve cells have died off or never developed in the first place. Recent research reported by Paulus found that grey matter volume increased by 8 per cent after four weeks lithium treatment of patients with bipolar disorder.
These results prompted researchers to investigate lithium's effect on various diseases characterised by degeneration of neurons, eg Alzheimer's and Huntington's disease and stroke which leads to the death of neurons. Recent research on mice genetically susceptible to developing Alzheimer's disease has shown that lithium treatment diminishes or prevents the development of certain hallmarks of the disease. Also, some preliminary data indicates that human sufferers of bipolar disorder who have been under lithium treatment are less likely to develop Alzheimer's disease than sufferers not taking lithium.
Stroke commonly results in neuronal death when arteries feeding the brain fail and the brain becomes starved of oxygen. Research with rats indicates that lithium may reduce brain damage if administered within three hours after stroke. Lithium might therefore work as an acute treatment for stroke as well as limiting damage in people at high risk of stroke.
Schizophrenia may result from loss of certain brain cells and failure of others to grow and develop, both features that lithium seems to be able to counteract. Recent studies on young adults genetically predisposed to develop schizophrenia suggest that lithium may have a strong protective effect against the development of this condition.
Trials are needed to gauge the value of lithium. They are usually funded by pharmaceutical companies, but these companies are not funding lithium trials because lithium is a natural element and they cannot patent the metal. Pharmaceutical companies make money by discovering new treatments and patenting and marketing them. In this case, surely, governments should step in and fund the necessary research and subsequent trials that could eventually see lithium alleviate suffering.
William Reville is associate professor of biochemistry and Public Awareness of Science Officer at UCC - http://understandingscience.ucc.ie