Inositol, Lithium, and the Brain

This review of the background and present state of knowledge of the interactions of inositol metabolism and lithium commemorates the 150th anniversaries of the discovery of inositol and, independently, of first attempts to use lithium as a therapeutic agent. We review the inositol depletion hypothesis, which proposes that lithium's beneficial action in the treatment of bipolar disorder is attributable to its inhibition of the enzymatic breakdown of inositol phosphates to free inositol. A resulting reduction in free intracellular inositol is proposed to slow the recycling of inositol-containing metabolites required for signal transduction. We offer an alternative hypothesis, which is also based on lithium's blockade of inositol phosphatase, but proposes that neural signal transduction is suppressed as a consequence of lithium-induced inositol phosphate accumulation rather than of inositol depletion.