Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited.
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.
Harwood
A J
AJ
MRC Laboratory for Molecular Biology, Department of Biology, University College London, London, UK. a.harwood@ucl.ac.uk
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007294:Inositol / Q000172:deficiency / Q000378:metabolism*; D018020:Lithium Compounds / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology*
D018692:Antimanic Agents; D018020:Lithium Compounds; D007294:Inositol; D014635:Valproic Acid