Lithium and valproate and their possible effects on themyo-inositol second messenger system in healthy volunteers and bipolar patients

@article{Silverstone2009LithiumAV,
  title={Lithium and valproate and their possible effects on themyo-inositol second messenger system in healthy volunteers and bipolar patients},
  author={Peter H. Silverstone and Brent M McGrath},
  journal={International Review of Psychiatry},
  year={2009},
  volume={21},
  pages={414 - 423}
}
Over 25 years ago it was suggested that the mechanism by which lithium was clinically effective may be due to a stabilizing effect on the phosphoinositol second messenger system (PI-cycle), which has multiple effects within cells. It was proposed that lithium, which is an inhibitor of one of the key enzymes in the PI-cycle, acted to lower myo-inositol concentrations; termed the ‘inositol-depletion hypothesis’. Initial animal evidence supported this hypothesis, and also suggested that it was… 

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The objective of the present study was to test the hypothesis that chronic treatment with either lithium or sodium valproate in patients with bipolar mood disorder leads to a normalization in the activity of the PI‐cycle.

A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI‐cycle) to psychiatric disorders—focus on magnetic resonance spectroscopy (MRS) studies

While the evidence suggests probable relevance to the pathophysiology and/or treatment of bipolar disorder, there is much less support for a significant role for the PI‐cycle or myo‐inositol in any other psychiatric disorder.

Lithium and valproate protect against dextro-amphetamine induced brain choline concentration changes in bipolar disorder patients

Findings show that while in controls dextro-amphetamine decreases choline concentrations, lithium and valproate both appear to protect against this effect in bipolar patients, however, as brain ratios were measured rather than the absolute concentration of choline, these results must be regarded as preliminary and require replication in future studies.

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Lithium does not attenuate the effects of d-amphetamine in healthy volunteers

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The ability of Li+ to greatly amplify the agonist-dependent accumulation of myo-inositol 1-phosphate offers a novel technique for identifying those receptors that function by hydrolysing phosphatidyl inositol, which may help reset the sensitivity of those multifunctional receptors that generate second messengers such as Ca2+, cyclic GMP and the prostaglandins.
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