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The high affinity inositol transport system – implications for the pathophysiology and treatment of bipolar disorder

Authors


Corresponding author: Dietrich van Calker, PhD, MD, Department of Psychiatry, University of Freiburg, Hauptstraße 5, D-79104 Freiburg, Germany. Fax: +49 761 270 6619; e-mail: dietrich_van_calker@psyallg.ukl.uni-freiburg.de

Abstract

The ‘inositol-depletion hypothesis’ postulates that the therapeutic effects of lithium are due to inhibition of inositol monophosphatase, which leads to depletion of brain cells of myo-inositol and consequently to dampening of phosphoinositide (PI) signaling. This article examines the potential relevance of an alternative mechanism for inositol depletion: inhibition of myo-inositol uptake that proceeds via the sodium/myo-inositol cotransport (SMIT). We discuss recent in vitro experiments that show a pronounced downregulation of SMIT after chronic treatment with lithium, carbamazepine, and valproate at therapeutically relevant concentrations. It is concluded that downregulation of SMIT could represent a common mechanism of action of mood stabilizers.

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