Defining the neuromolecular action of myo-inositol: application to obsessive-compulsive disorder

Dietary inositol is incorporated into neuronal cell membranes as inositol phospholipids where it serves as a key metabolic precursor in G protein-coupled receptors. In the brain, several subtypes of adrenergic, cholinergic, serotonergic and metabotropic glutamatergic receptors are coupled to the hydrolysis of phosphoinositides (PI) with myo-inositol (MI) crucial to the resynthesis of PI and the maintenance and effectiveness of signalling. Despite a mode of action that remains illusive, MI has demonstrated therapeutic efficacy in obsessive-compulsive disorder (OCD), putative OCD-spectrum disorders, as well as panic and depression. Behavioural and biochemical studies indicate that this efficacy does not involve simply the replenishing of the membrane PI pool. In addition to its precursory role in cell signalling, inositol lipids alter receptor sensitivity, can direct membrane trafficking events, and have been found to modulate an increasing array of signalling proteins. These effects may afford MI an ability to modulate the interaction between neurotransmitters, drugs, receptors and signalling proteins. This paper reviews the neuromolecular and genetic aspects of OCD in terms of the PI-linked 5HT receptor subtypes and relates these to the behavioural and therapeutic effects of MI. Since OCD often is poorly responsive to current drug treatment, understanding the neuropharmacology of MI holds great promise for understanding the neuropathology of this and other MI-responsive disorders.