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Home » Bipolar Disorder

Psychiatric Times. Vol. 16 No. 12
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Omega-3 Fatty Acids Evaluated for Bipolar Disorder

By Arline Kaplan | December 1, 1999

"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(Drug information on lithium) and valproate(Drug information on 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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References

Barton PG, Gunstone FD (1975), Hydrocarbon chain packing and molecular motion in phospholipid bilayers formed from unsaturated lecithins. Synthesis and properties of sixteen positional isomers of 1,2-dioctadecenolyl-sn-glycero-3-phosphorylcholine. J Biol Chem 250(12):4470-4476.

Berridge MJ, Downes CP, Hanley MR (1982), Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J 206(3):587-595.

Chen G, Manji HK, Hawver DB et al. (1994), Chronic sodium valproate selectively decreases protein kinase C alpha and epsilon in vitro. J Neurochem 63(6):2361-2364.

Edwards R, Peet M, Shay J, Horrobin D (1998), Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J Affect Disord 48(2-3):149-155.

Hibbeln JR (1998a), Fish consumption and major depression. Lancet 351(9110):1213 [letter].

Hibbeln JR, Linnoila M, Umhau JC et al. (1998b), Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics. Biol Psychiatry 44(4):235-242.

Manji HK, Bersudsky Y, Chen G et al. (1996), Modulation of protein kinase C isozymes and substrates by lithium: the role of myo-inositol.
Neuropsycho-pharmacology 15(4):370-381.

McLean Hospital (1999), Study finds fish oil relieves symptoms of manic depression. Available at: www.mcleanhospital.org/PublicAffairs/199905b_FishOil.htm. Accessed July 13.

Medini L, Colli S, Mosconi C et al. (1990), Diets rich in n-9, n-6 and n-3 fatty acids differentially affect the generation of inositol phosphates and of thromboxane by stimulated platelets, in the rabbit. Biochem Pharmacol 39(1):129-133.

National Institute of Mental Health (1999), Omega-3 fatty acids in treatment of major depression and bipolar disorder: a double-blind placebo-controlled study. Clinical Research Study 99-M-0181. Available at: clinicalstudies.info.nih.nimh. gov.cgi/detail.cgi?A_99-M-0181.html. Accessed Oct. 19.

Sperling RI, Benincaso AI, Knoell CT et al. (1993), Dietary omega-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. J Clin Invest 91(2):651-660. Stoll AL, Marangell LB (1999), In reply. Arch Gen Psychiatry 56(5):415-416.

Stoll AL, Severus WE (1996), Mood stabilizers: shared mechanisms of action at postsynaptic signal-transduction and kindling processes. Harv Rev Psychiatry 4(2):77-89.

Stoll AL, Severus WE, Freeman MP et al. (1999), Omega 3 fatty acids in bipolar disorder. A preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry 56(5):407-412.


 
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