Why lithium is doubly effective – perhaps

Why lithium is doubly effective – perhaps – for manic-depressives

Gina Maranto

For manic-depressives lithium is the great equalizer. Since the 1970s they’ve used the drug to temper their mood swings, but they’ve taken it — and their doctors have prescribed it — on faith. Nobody knew how it worked. But a recent theory suggests an answer.

Mood disorders are thought to be caused by imbalances in the brain’s neurotransmitters, the chemicals by which brain cells communicate with one another. Neurotransmitters from one cell bind to the outside of another cell and initiate a series of biochemical events inside it that deter- mine how it will fire. If a particular neurotransmitter, or ”first messenger,” goes haywire, the cell manufactures too little or too much ”second messenger” inside, causing the cell to fire abnormally and producing an exaggerated mood.

Most mood-altering drugs work by increasing or decreasing the amount of transmitter that reaches a cell. However, for manic-depressives such drugs aren’t very effective. For one thing, each drug can be used for only one kind of mood swing, because each affects only a specific type of transmitter: anti-psychotics treat mania by blocking the transmitters that trigger it, but they do nothing for a patient in a depressive phase; antidepressants not only won’t combat mania but have even been known to precipitate it. Furthermore, such mood-altering drugs are indiscriminate: they act on neurotransmitters whether or not they’ve gone haywre.

Lithium has none of these drawbacks. It relieves both mania and depression, and even protects against further mood swings. What makes it work this way? Neuroscientists Solomon Snyder, Jay Bar- aban, and Paul Worley of Johns Hopkins suggest that the key to lithium’s paradoxical effects is its site of intervention: unlike most other drugs, it bypasses the neurotransmitters on the outside and goes right to the second-messenger system at the heart of the cell. When the cell is hyperac tive — when a faulty signal from one neurotransmitter or another is making it produce too much second messenger — lithium will act as an inhibitor. In mood disorders, the researchers propose, lithi- um drives hyperactive cells back to normal, whether those cells are causing mania or depression. And when the cells are doing their job just right, lithium leaves them alone. As Baraban puts its, ”It’s like a traffic cop who makes sure you’re not going too fast or too slow.”

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