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Lithium: The First Mood Stabilizer

Part 1: History and a Mystery Solved


Updated June 02, 2014

Lithium, discovered in 1817, was noticed to have mood stabilizing properties in the late 1800s when doctors were using it to treat gout. (At least one doctor, in fact, concluded from this that gout was the cause of mood disorders.) It was Australian psychiatrist John Cade who, in 1949, published the first paper on the use of lithium in the treatment of acute mania. The U.S. Food and Drug Administration did not approve lithium for use until 1970.

Research has never indicated that that bipolar disorder might be caused by a lithium deficiency. Rather, it happens that this naturally occurring substance has the fortunate effect of acting as a mood stabilizer.

Lithium's First Answers in 1998

For almost 50 years, manic-depressive people were treated with lithium even though medical science did not know why or how it worked. Then in 1998, University of Wisconsin researchers unlocked the mystery. The secret of lithium has to do with nerve cells in the brain, and the receptors for the neurotransmitter glutamate.

As I described in the article Messengers of the Brain, neurotransmitters are released from one neuron (nerve cell) and may bond to the receptors of a neighboring cell or be picked up by autoreceptors from the releasing cell (among other things). The result varies depending on what the type of receiving cell and the type of neurotransmitter.

Lithium and Glutamate Stabilization

The University of Wisconsin researchers found that lithium exerts a dual effect on receptors for the neurotransmitter glutamate - acting to keep the amount of glutamate active between cells at a stable, healthy level, neither too much nor too little.

UW Medical School professor of pharmacology Dr. Lowell Hokin, who directed the research, said that from their research it could be postulated that too much glutamate in the space between neurons causes mania, and too little, depression. There has to be more to it than that, since antidepressant medications, for example, work on the receptors of other neurotransmitters such as serotonin and dopamine. However, this was certainly a giant step forward in understanding the biological basis of bipolar disorder.

Note: a large amount of extra glutamate can lead to epileptic seizures or even kill the second cell from overstimulation. Because of lithium's stabilizing effect on glutamate receptors, scientists are also studying whether this medication can protect from the cell death that occurs in conditions such as Parkinson's, Huntington's and Alzheimer's.

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