"The precise mechanism of this effect remains unclear. However, the incorporation of the polyunsaturated omega-3 fatty acids into the lipid bilayer of the cell membrane alters the physical and chemical properties of the membrane [Barton and Gunstone, 1975], possibly producing a local environment in which the membrane phospholipids are more resistant to hydrolysis by phospholipases. This could result in reduced generation of the second messenger molecules diacylglycerol and inositol triphosphate, thereby producing less activation of 'downstream' intracellular signaling molecules, such as protein kinase C and calcium ionýIt is possible that the omega-3 fatty acids also inhibit signal transduction mechanisms in the human central nervous system. Recent work by several investigators [Berridge et al., 1982; Chen et al., 1994; Manji et al., 1996; Stoll and Severus, 1996] strongly suggests that the mechanism of action of typical mood stabilizers, such as lithium and valproate [Depakote], involves a similar inhibition of postsynaptic signal transduction processes."

In addition to the Harvard/Baylor study, a double-blind, placebo-controlled trial will examine the efficacy of omega-3 fatty acids in the form of EPA for treatment of BD. Five NIMH-Stanley Foundation Bipolar Network sites are participating in the project. Subjects will be randomly assigned in a double-blind manner to 6 g/day of EPA or placebo as an add-on to ongoing treatment with mood-stabilizing medications that have proven unsatisfactorily effective within therapeutic range(s) or at maximum tolerated doses. At the end of the four-month double-blind trial, patients can enter an eight-month, open-label trial of omega-3 fatty acid (National Institute of Mental Health, 1999).

Research is occurring on the effect of omega-3 fatty acids on several psychiatric disorders, including major depression (Edwards et al., 1998; Hibbeln et al., 1998a, 1998b), schizophrenia and attention-deficit/hyperactivity disorder (ADHD).
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