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First published June 2007

Preliminary in vivo evidence of increased N-acetyl-aspartate following eicosapentanoic acid treatment in patients with bipolar disorder

Abstract

EthyL-eicosapentanoic acid (ethyL-EPA) may be beneficial in the treatment of bipolar disorder (BD) and may have a neurotrophic/neuroprotective role in patients with neuropsychiatric disorders. To investigate this we examined whether ethyl-EPA treatment of BD patients is associated with increased brain Levels of N-acetylaspartate (NAA), a putative marker of neuronal integrity. Fourteen female BD outpatients with moderate depressive symptoms were administered 2g of ethyL-EPA per day or placebo for 12 weeks in a randomized, double-blind fashion. Quantitative, proton magnetic resonance spectroscopy imaging data were obtained prior to randomization and after 12 weeks of treatment from a single 12 ml volume of interest centred above the body of the corpus callosum. A significant rise in NAA Levels was observed in the ethyl-EPA treatment group compared with the placebo group (p = 0.027). These results provide the first evidence for a probable neurotrophic role of ethyl-EPA treatment in BD underlining the need for more detailed investigation of its mechanism of action and therapeutic potential.

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References

American Psychiatry Association (1994) Diagnostic and Statistical Manual of Mental disorders, 4th edn. American Psychiatric Press, Washington, DC
Armstrong V.T., Brzustowicz M.R., Wassall S.R., Jenski L.J., Stillwell W. (2003) Rapid flip-flop in polyunsaturated (docosahexaenoate) phospholipid membranes . Arch Biochem Biophys 414: 74—82
Bogazzi F., Hudson L.D., Nikodem V.M. (1994) A novel heterodimerization partner for thyroid hormone receptor. Peroxisome proliferator-activated receptor . J Biol Chem 269: 11683—11686
Chakraborty G., Mekala P., Yahya D., Wu G., Ledeen R.W. (2001) Intraneuronal N-acetylaspartate supplies acetyl groups for myelin lipid synthesis: evidence for myelin-associated aspartoacylase . J Neurochem 78: 736—745
First M.B., Spitzer R.L., Gibbon M., Williams J B W (2001) Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P). Biometrics Research, New York State Psychiatric Institute, New York
Frangou S., Lewis M., McCrone P. (2006) Efficacy of two doses of ethyl eicosapentaenoate (ethyl-EPA) as adjunct therapy in the acute treatment of bipolar 1 depression. Br Journal Psychiatry 188: 46—50
Haldane M., Frangou S. (2004) New insights help define the pathophysiology of bipolar affective disorder: neuroimaging and neuropathology findings . Prog Neuropsychopharmacol Biol Psychiatry 28: 943—960
Hamilton M. (1960) A rating scale for depression . J Neurol Neurosurg Psychiatry 23: 56—62
MacQueen G.M., Young L.T., Joffe R.T. (2001) A review of psychosocial outcome in patients with bipolar disorder . Acta Psychiatr Scand 103: 163—170
Manji H.K., Moore G.J., Chen G. ( 1999) Lithium at 50: have the neuroprotective effects of this unique cation been overlooked? Biol Psychiatry 46: 929—940
Moore G.J., Bebchuk J.M., Hasanat K., Chen G., Seraji-Bozorgzad N., Wilds I.B., Faulk M.W., Koch S., Glitz D.A., Jolkovsky L., Manji H.K. (2000) Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2's neurotrophic effects? Biol Psychiatry 48: 1—8
Nemets B., Stahl Z., Belmaker R.H. (2002) Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder . Am J Psychiatry 159: 477—479
Peet M., Horrobin D.F. (2002) A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs . Arch Gen Psychiatry 59: 913—919
Provencher S.W. (1993) Estimation of metabolite concentrations from localised in vivo proton NMR spectra . Magn Reson Med 30: 672—679
Puri B.K., Holmes J., Hamilton G. (2004) Eicosapentaenoic acid-rich essential fatty acid supplementation in chronic fatigue syndrome associated with symptom remission and structural brain changes . Int J Clin Pract 58: 297—299
Puri B.K., Counsell S.J., Hamilton G., Richardson A.J., Horrobin D.F. (2001) Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover . Int J Clin Pract 55: 560—563
Puri B.K., Bydder G.M., Counsell S.J., Corridan B.J., Richardson A.J., Hajnal J.V., Appel C., Mckee H.M., Vaddadi K.S., Horrobin D.F. (2002) MRI and neuropsychological improvement in Huntington disease following ethyl-EPA treatment . Neuroreport 13: 123—126
Saluja I., Granneman J.G., Skoff R.P. (2001) PPAR delta agonists stimulate oligodendrocyte differentiation in tissue culture . Glia 33: 191—204
Salvati S., Natali F., Attorri L., Raggi C., Di Biase A, Sanchez M. (2004) Stimulation of myelin proteolipid protein gene expression by eicosapentaenoic acid in C6 glioma cells . Neurochem Int 44: 331—338
Seung Kim H.F., Weeber E.J., Sweatt J.D., Stoll A.L., Marangell L.B. (2001) Inhibitory effects of omega-3 fatty acids on protein kinase C activity in vitro . Mol Psychiatry 6: 246—248
Simmons A., Smail M., Moore E., Williams S C R (1998) Serial precision of metabolite peak areas in proton MR spectroscopy of the human brain . Magn Reson Imaging 16: 319—330
Soares J.C. (2003) Contributions from brain imaging to the elucidation of pathophysiology of bipolar disorder . Int J Neuropsychopharmacol 6: 171—180
Stoll A.L., Severus W.E. (1996) Mood stabilizers: shared mechanisms of action at postsynaptic signal-transduction and kindling processes . Harv Rev Psychiatry 4: 77—89
Stoll A.L., Severus W.E., Freeman M.P., Rueter S., Zboyan H.A., Diamond E., Cress K.K., Marangell L.B. (1999) Omega-3 fatty acids in bipolar disorder: a preliminary double blind, placebo controlled trial . Arch Gen Psychiatry 56: 407—412
Tkachev D., Mimmack M.L., Ryan M.M., Wayland M., Freeman T., Jones P.B., Starkey M., Webster M.J., Yolken R.H., Bahn S. ( 2003) Global expression-profiling studies and oligodendrocyte dysfunction in schizophrenia and bipolar disorder . Lancet 362: 798—805
Tsai G., Coyle J.T. (1995) N-acetylaspartate in neuropsychiatric disorders . Prog Neurobiol 46: 531—540

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Published In

Article first published: June 2007
Issue published: June 2007

Keywords

  1. bipolar disorder
  2. omega-3 fatty acid
  3. eicosapentanoic acid
  4. magnetic resonance spectroscopy

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PubMed: 16891338

Authors

Affiliations

Sophia Frangou
Section of Neurobiology of Psychosis, Institute of Psychiatry, Kings College London, London, UK., [email protected]
MichaeL Lewis
Section of Neurobiology of Psychosis, Institute of Psychiatry, Kings College London, London, UK
James Wollard
Section of Neurobiology of Psychosis, Institute of Psychiatry, Kings College London, London, UK
Andrew Simmons
Neuroimaging Research Group, Institute of Psychiatry, Kings College London, London, UK

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