Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited

Mol Psychiatry. 2005 Jan;10(1):117-26. doi: 10.1038/


Inositol, a simple six-carbon sugar, forms the basis of a number of important intracellular signaling molecules. Over the last 35 years, a series of biochemical and cell biological experiments have shown that lithium (Li(+)) reduces the cellular concentration of myo-inositol and as a consequence attenuates signaling within the cell. Based on these observations, inositol-depletion was proposed as a therapeutic mechanism in the treatment of bipolar mood disorder. Recent results have added significant new dimensions to the original hypothesis. However, despite a number of clinical studies, this hypothesis still remains to be either proven or refuted. In this review of our current knowledge, I will consider where the inositol-depletion hypothesis stands today and how it may be further investigated in the future.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antimanic Agents / pharmacology
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / metabolism
  • Bipolar Disorder / physiopathology*
  • Brain / drug effects
  • Brain / physiopathology
  • Humans
  • Inositol / deficiency
  • Inositol / metabolism*
  • Lithium Compounds / pharmacology*
  • Signal Transduction / drug effects
  • Valproic Acid / pharmacology*


  • Antimanic Agents
  • Lithium Compounds
  • Inositol
  • Valproic Acid