New clue stirs up lithium mystery

Still a popular choice for the treatment of manic depression despite the emergence of more-modern drugs, lithium is an enigma. No one really knows how it evens out the moods of people with so-called bipolar disorders.

In the May 16 Nature, Adrian J. Harwood of University College London and his colleagues report that lithium and two other mood-stabilizing drugs–carbamazepine and valproic acid–may all work by depleting nerve cells of inositol, a chemical that the cells use to signal each other. The investigators report that in lab dishes, the drugs affect nerve cell extensions known as growth cones by, for example, increasing their size. Adding inositol to the cells, however, reverses those effects.

That three chemically distinct drugs for manic depression deplete the same neurotransmitter, inositol, is more than coincidence, the researchers argue in their report. “These results suggest a molecular basis for both bipolar affective disorder and its treatment,” they conclude.

Lithium investigator De-Maw Chuang of the National Institute of Mental Health in Bethesda, Md., is more cautious, suggesting that the drugs may have other molecular actions in common. “I wouldn’t say that this work has solved the long-standing mystery of lithium and other mood stabilizers,” he says.

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