Schizophrenia Research
Volume 49, Issue 3 , Pages 243-251 , 30 April 2001

Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia

  • Malcolm Peet

      Affiliations

    • Academic Department of Psychiatry, Northern General Hospital, The Longley Centre, Norwood Grange Drive, Sheffield S5 7JT, UK
    • Corresponding Author InformationCorresponding author. Tel.: +44-114-2261509; fax: +44-114-2261522
    • ,
  • Jan Brind

      Affiliations

    • Academic Department of Psychiatry, Northern General Hospital, The Longley Centre, Norwood Grange Drive, Sheffield S5 7JT, UK
    • ,
  • C.N. Ramchand

      Affiliations

    • Academic Department of Psychiatry, Northern General Hospital, The Longley Centre, Norwood Grange Drive, Sheffield S5 7JT, UK
    • ,
  • Sandeep Shah

      Affiliations

    • Department of Psychiatry, S.S.G. Hospital and Medical College, M.S. University, Baroda, India
    • ,
  • G.K. Vankar

      Affiliations

    • Department of Psychiatry, S.S.G. Hospital and Medical College, M.S. University, Baroda, India

Received 28 March 2000 ,Accepted 9 May 2000.

References 

  1. Abedin L, Lien EL, Vingrys AJ, Sinclair AJ. The effects of dietary alpha-linolic acid compared with docosahexaenoic acid on brain, retina, liver and heart in the guinea pig. Lipids. 1999;34:475–482
  2. Albers MA, Meurer H, Märki F, Klotz J. Phosopholipase A2 activity in serum of neuroleptic-naı̈ve psychiatric in patients. Pharmacopsychiatry. 1993;26:94–98
  3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). fourth ed.. Washington, DC: American Psychiatric Association; 1994;
  4. Bates EJ, Ferrante A, Harvey DP, Nandoskar M, Poulos A. Docosahexaenoic acid (22:6, n-3) but not eicosapentaenoic acid (20:5, n-3) can induce neutrophil-mediated injury of cultured endothelial cells: involvement of neutrophil elastase. J. Leukoc. Biol. 1993;54:590–598
  5. Christensen O, Christensen E. Fat consumption and schizophrenia. Acta Psychiatr. Scand. 1998;78:587–591
  6. Collaborative Working Group on Clinical Trial Evaluation. Adverse effects of the atypical antipsychotics. J. Clin. Psychiatry. 1998;59(12):17–22
  7. Connor SL, Connor WE. Are fish oils beneficial in the prevention and treatment of coronary artery disease?. Am. J. Clin. Nutr. 1997;66(4):1020S–1031S
  8. De Caterina R, Cybulsky MI, Clinton SK, Gimbrone MA, Libby P. The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells. Arterioscler. Thromb. 1994;14:1829–1836
  9. Delion S, Chalon S, Guilloteau D, Besnard JC, Durand G. Alpha-linolenic acid dietary deficiency alters age-related changes of dopaminergic and serotoninergic neurotransmission in the rat frontal cortex. J. Neurochem. 1996;66:1582–1591
  10. Eaton WW, Hayward C, Ram R. Schizophrenia and rheumatoid arthritis: a review. Schizophr. Res. 1992;6:181–192
  11. Finnen MJ, Lovell CR. Purification and characterisation of phospholipase A2 from human epidermis. Biochem. Soc. Trans. 1991;19:91
  12. Fukuzako H, Fukuzako T, Hashiguchi T, Kodama S, Takigawa M, Fujimoto T. Changes in levels of phosphorus metabolites in temporal lobes of drug-naı̈ve schizophrenic patients. Am. J. Psychiatry. 1999;156:1205–1208
  13. Gattaz WF, Kollisch M, Thuren T, Virtanen JA, Kinnunen PKJ. Increased plasma phospholipase-A2 activity in schizophrenic patients: reduction after neuroleptic therapy. Biol. Psychiatry. 1987;22:421–426
  14. Gattaz WF, Hubner CK, Nevalainen TJ, Thuren T, Kinnimen PKJ. Increased serum phospholipase-A2 activity in schizophrenia: a replication study. Biol. Psychiatry. 1990;28:495–501
  15. Gattaz WF, Schmitt A, Maras AM. Increased platelet phospholipase A2 activity in schizophrenia. Schizophr. Res. 1995;16:1–6
  16. Gilbert M, Achard F, Dalloz S, Maclouf J, Benistant C, Legarde M. Opposite regulation of prostaglandin H synthase isoforms by eicosapentaenoic and docosahexaenoic acids. Lipids. 1999;34:219
  17. Glen A, Glen EM, Horrobin DF, Vaddadi KS, Spellman M, Morse-Fisher N, et al. A red cell membrane abnormality in a subgroup of schizophrenic patients: evidence for two diseases. Schizophr. Res. 1994;12:53–61
  18. Hitzemann RJ, Mark C, Hirschowitz J, Garver DL. Characteristics of phospholipid methylation in human erythrocyte ghosts: relationship to the psychoses and affective disorders. Biol. Psychiatry. 1985;20:297–307
  19. Horrobin DF, Manku MS, Hillman S, Glen AI. Fatty acid levels in the brains of schizophrenics and normal controls. Biol. Psychiatry. 1991;30:795–805
  20. Horrobin DF. The membrane phospholipid hypothesis as a biochemical basis for the neurodevelopmental hypothesis of schizophrenia. Schizophr. Res. 1998;30:193–208
  21. Howe PR, Clifton PM, James MJ. Equal antithrombotic and triglyceride-lowering effectiveness of eicosapentaenoic acid-rich and docosahexaenoic acid-rich fish oil supplements. Lipids. 1999;34:S307–S308
  22. Kane JM, Jeste DV, Barnes TE, Casey DE, Cole JO, Davis JM, et al. Tardive Dyskinesia: A Task Force Report of the American Psychiatric Association. Washington, DC: APA; 1992;
  23. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull. 1987;13:261–276
  24. Keshaven MS, Mallinger AG, Pettegrew JW, Dippold C. Erythrocyte membrane phospholipids in psychotic patients. Psychiatry Res. 1993;49:89–95
  25. Litman BJ, Mitchell DC. A role for phospholipid polyunsaturation in modulating membrane protein function. Lipids. 1996;31:S193–S197
  26. Loh HH, Law PY. Role of membrane lipids in receptor mechanisms. Ann. Rev. Pharmacol. Toxicol. 1980;20:201–234
  27. Mahadik SP, Mukherjee S, Correnti EE, Kelkar HS, Wakade CG, Costa RM, et al. Plasma membrane phospholipid and cholesterol distribution of skin fibroblasts from drug-naı̈ve patients at the onset of psychosis. Schizophr. Res. 1994;13:239–247
  28. Manku MS, Horrobin DF, Huang S, Morse N. Fatty acids in plasma and red cell membranes. Lipids. 1983;18:906–908
  29. Marteinsdottir I, Horrobin DF, Stenfors C, Theodorsson E, Mathe AA. Changes in dietary fatty acids alter phospholipid fatty acid composition in selected regions of rat brain. Prog. Neuropsychopharmacol. Biol. Psychiatry. 1998;22:1007–1021
  30. Mellor J, Laugharne JDE, Peet M. Omega-3 fatty acid supplementation in schizophrenic patients. Human Psychopharmacol. 1996;11:39–46
  31. Morrow JD, Awad JA, Oates JA, Roberts LJ. Identification of skin as a major site of prostaglandin D2 release following oral administration of niacin in humans. J. Invest. Dermatol. 1992;98:812–815
  32. Noponen M, Sanfilipo M, Samanich K, Ryer H, Ko G, Angrist B, et al. Elevated PLA2 activity in schizophrenics and other psychiatric disorders. Biol. Psychiatry. 1993;34:641–649
  33. Obata T, Nagakura T, Masaki T, Masaki T, Maekawa K, Yamashita K. Eicosapentaenoic acid inhibits prostaglandin D2 generation by inhibiting cyclo-oxygenase-2 in cultured human mast cells. Clin. Exp. Allergy. 1999;29:1129–1135
  34. Okuda Y, Ezure M, Tsukahara K, Sawada T, Mizutani M, Katori T, et al. Eicosapentaenoic acid enhances intracellular free calcium in cultured human endothelial cells. Biochem. Med. Metab. Biol. 1994;51:166–168
  35. Pangerl AM, Steudle A, Jaroni HW, Rufer R, Gattaz WF. Increased platelet membrane lysophosphatidylcholine in schizophrenia. Biol. Psychiatry. 1991;30:837–840
  36. Peet M, Laugharne JDE, Rangarajan N, Horrobin DF, Reynolds G. Depleted red cell membrane essential fatty acids in drug-treated schizophrenic patients. J. Psychiatr. Res. 1995;29:227–232
  37. Peet M, Laugharne JDE, Mellor J. Double-blind trial of fatty acid supplementation in the treatment of schizophrenia. International Congress on Schizophrenia Research, Colorado Springs, CO, April. 1997;
  38. In:  Peet M,  Glen I,  Horrobin DF editor. Phospholipid Spectrum Disorder in Schizophrenia. Carnforth, UK: Marius Press; 1999;
  39. Pettegrew JW, Keshevan MS, Panchalingam K, Strychor S, Kaplan TB, Tretta MG, et al. Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drug-naı̈ve schizophrenics. A pilot study of the dorsal prefrontal cortex by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy. Arch. Gen. Psychiatry. 1991;48:563–568
  40. Puri BK, Richardson AJ. Sustained remission of positive and negative symptoms of schizophrenia following treatment with eicosapentaenoic acid. Arch. Gen. Psychiatry. 1998;55:188–189
  41. Ross BM, Hudson C, Erlich J, Warsh JJ, Kish SJ. Increased phospholipid breakdown in schizophrenia: evidence for the involvement of a calcium-independent phospholipase A2. Arch. Gen. Psychiatry. 1997;54:487–494
  42. Ross BM. Brain and blood phospholipase activity in psychiatric disorders. In:  Peet M,  Glen I,  Horrobin DF editor. Phospholipid Spectrum Disorder in Psychiatry. Carnforth, UK: Marius Press; 1999;p. 23–29
  43. Rudin DO. The major psychoses and neuroses as omega-3 essential fatty acid deficiency syndrome: substrate pellagra. Biol. Psychiatry. 1981;16:837–848
  44. Shah S, Vankar GK, Telang SD, Ramchand CN, Peet M. Eicosapentaenoic acid (EPA) as an adjunct in the treatment of schizophrenia. 9th Biennial Winter Workshop on Schizophrenia, Davos, Switzerland, February. 1998;
  45. Shah S, Vankar K, Ramchand CN, Peet M. Lack of niacin skin flush response in unmedicated schizophrenic patients. Schizophr. Res. 2000;in press
  46. Stanley JA, Williamson PC, Drost DJ, Carr TJ, Rylett RJ, Morrison-Stewart S, et al. Membrane phospholipid metabolism and schizophrenia: in vivo 31P-MR spectroscopy study. Schizophr. Res. 1994;13:209–215
  47. Sumida C, Graber R, Nunez E. Role of fatty acids in signal transduction: modulators and messengers. Prostaglandins Leukot. Essent. Fatty Acids. 1993;48:117–122
  48. Tisdale MJ. Mechanism of lipid mobilisation associated with cancer cachexia: interaction between the polyunsaturated fatty acid, eicosapentaenoic acid and inhibitory guanine nucleotide-regulatory protein. Prostaglandins Leukot. Essent. Fatty Acids. 1993;48:105–109
  49. Trzeciak HI, Kalacinski W, Malecki A, Kokot D. Effect of neuroleptics on phospholipase A2 activity in the brain of rats. Eur. Arch. Psychiatry. Clin. Neurosci. 1995;245:179–182
  50. Tsuang MT, Stone WS, Serdman LJ, Faraone SV, Zimmet S, Wojcik J, et al. Treatment of non-psychotic relatives of patients with schizophrenia: four case studies. Biol. Psychiatry. 1999;45:1412–1418
  51. Vaddadi KS, Gilleard CJ, Mindham RHS, Butler RA. A controlled trial of a prostaglandin E1 precursor in chronic neuroleptic-resistant schizophrenic patients. Psychopharmacology. 1986;88:362–367
  52. Vaddadi KS, Courtney P, Gilleard CJ, Manku MS, Horrobin DF. A double blind trial of essential fatty acid supplementation in patients with tardive dyskinesia. Psychiatry Res. 1989;27:313–323
  53. Waddington JL, Scully PJ, O'Callaghan E. The new antipsychotics and their potential for early intervention in schizophrenia. Schizophr. Res. 1997;28:207–222
  54. Ward PE, Sutherland J, Glen EMT, Glen AIM. Niacin skin flush in schizophrenia a preliminary report. Schizophr. Res. 1998;29:269–274
  55. Warner R, Laugharne J, Peet M, Brown L, Rogers N. Retinal function as a marker for cell membrane omega-3 fatty acid depletion in schizophrenia: a pilot study. Biol. Psychiatry. 1999;45:1138–1142
  56. Willumsen N, Vaagenes H, Lie O, Rustan AC, Berge RK. Eicosapentaenoic acid, but not docosahexaenoic acid, increases mitochondrial fatty acid oxidation and upregulates 2,4-dienoyl-CoA reductase gene expression in rats. Lipids. 1996;31:579–592
  57. Wolkin A, Jordan B, Peselow E, Rubinstein M, Retrosen J. Essential fatty acid supplementation in tardive dyskinesia. Am. J. Psychiatry. 1986;143:912–914
  58. Yao JK, van Kammen DP, Welker JA. Red blood cell membrane dynamics in schizophrenia II: fatty acid composition. Schizophr. Res. 1994;13:217–226
  59. Yao JK, van Kammen DP, Welker JA, Gurklis J. Red blood cell membrane dynamics in schizophrenia III. Correlation of fatty acid abnormalities with clinical measures. Schizophr. Res. 1994;13:227–232
  60. Yao JK. Red blood cell and platelet fatty acid metabolism in schizophrenia. In:  Peet M,  Glen I,  Horrobin DF editor. Phospholipid Spectrum Disorder in Schizophrenia. Carnforth, UK: Marius Press; 1999;p. 57–74
  61. Yokota K, Tsuruhamim K, Nishimura K, Nagayam T, Jisaka M, Takinami K. Modification of membrane phospholipids with n-6 and n-3 essential fatty acids regulates the gene expression of prostaglandin endoperoxide synthase isoforms upon agonist stimulation. In:  Riemersma RA,  Armstrong R,  Kelly RW,  Wilson R editor. Essential Fatty Acids and Eicosanoids. Invited Papers from the Fourth International Congress. Champaign, IL: AOCS Press; 1998;p. 68–73
  62. Yung AR, McGorry PD. Is pre-psychotic intervention realistic in schizophrenia and related disorders?. Aust. NZ J. Psychiatry. 1997;31:799–805
  63. Yung AR, Phillips LJ, McGarry PD, McFarlane CA, Francey S, Harrigan S, et al. Prediction of psychosis. A step towards indicated prevention of schizophrenia. Br. J. Psychiatry. 1998;172:14–20

PII: S0920-9964(00)00083-9

Schizophrenia Research
Volume 49, Issue 3 , Pages 243-251 , 30 April 2001

Article Tools

* Image Usage & Resolution