High resolution

Module 12: Figure Li+ action

The inositol depletion hypothesis for the control of manic-depressive illness by mood-stabilizing drugs such as Li+ and valproate.

The basis of this hypothesis is that Li+ and valproate modify the signalling pathways associated with the phosphoinositide lipids, which have many functions within the nervous system. The idea is that manic-depressive illness may arise when this signalling pathway is overactive. Li+ and valproate may function to reduce the activity of this pathway by reducing the supply of inositol used to replenish the membrane supply of inositol lipids. Neurons are uniquely sensitive to Li+ and valproate because they are denied access to plasma inositol, which fails to cross the blood–brain barrier.