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Changes in erythrocyte membrane fatty acids during a clinical trial of eicosapentaenoic acid (EPA) supplementation in schizophrenia

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Abstract

In a previously reported double-blind, placebo-controlled trial of eicosapentaenoic acid (EPA) as supplemental treatment in 40 patients with schizophrenia, we found significant improvement in symptoms as measured by the Positive and Negative Syndrome Scale (PANSS) compared to placebo (Emsley et al. 2002). Here we report changes in fatty acid composition of erythrocyte membranes in the same sample (n = 16 in each group). After 12 weeks of receiving EPA, levels of several saturated and mono-unsaturated fatty acids decreased significantly while levels of n-3 fatty acids increased significantly compared to the placebo group. Increases of n-3 and n-6 fatty acids in the erythrocyte membranes were greater in subjects who improved more than 20% on overall symptoms. Changes in fatty acids correlated significantly with improvement in PANSS sub-scale scores, more so in females than in males. Docosahexaenoic acid (DHA) (22:6n-3) levels increased less than expected, suggesting a possible defect in synthesis or incorporation of DHA into membranes in schizophrenia. Improvement in dyskinesia correlated significantly with an increase in alpha-linolenic acid (18:3n-3; p = 0.03), and a decrease in 20:1n-9 (p = 0.005).

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References

  • Christensen O, Christensen E (1988) Fat consumption and schizophrenia. Acta Psychiatr. Scand. 78:587–591

    Article  CAS  PubMed  Google Scholar 

  • Condray R, Yao JK, Steinhauer SR, van Kammen DP, Reddy RD, Morrow LA (2008) Semantic memory in schizophrenia: association with cell membrane essential fatty acids. Schizophr Res. 106:13–28

    Article  PubMed  Google Scholar 

  • De Hert M, Schreurs V, Vancampfort D, Van Winkel R (2009) Metabolic syndrome in people with schizophrenia: a review. World Psychiatry 8:15–22

    Google Scholar 

  • Emsley R, Myburgh C, Oosthuizen P, Van Rensburg SJ (2002) Randomized placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. Am. J. Psychiatry 159:1596–1598

    Article  PubMed  Google Scholar 

  • Emsley R, Oosthuizen P, Van Rensburg SJ (2003) Clinical Potential of Omega-3-Fatty Acids in the treatment of schizophrenia. CNS Drugs 17:1081–1091

    Article  CAS  PubMed  Google Scholar 

  • Emsley R, Niehaus DJ, Koen L, Oosthuizen PP, Turner HJ, Carey P, Van Rensburg SJ, Maritz JS, Murck H (2006) The effects of eicosapentaenoic acid in tardive dyskinesia: a randomized, placebo-controlled trial. Schizophr Res. 84:112–20

    Article  PubMed  Google Scholar 

  • Evans DR, Parikh VV, Khan MM, Coussons C, Buckley PF, Mahadik SP (2003) Red blood cell membrane essential fatty acid metabolism in early psychotic patients following antipsychotic drug treatment. Prostaglandins Leukot Essent Fatty Acids. 69:393–399

    Article  CAS  PubMed  Google Scholar 

  • Farooqui AA, Ong WY, Horrocks LA (2006) Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol Rev. 58:591–620

    Article  CAS  PubMed  Google Scholar 

  • Fenton WS, Dickerson F, Boronow J, Hibbeln JR, Knable MA (2001) Placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am. J. Psychiatry 158:2071–2074

    Article  CAS  PubMed  Google Scholar 

  • Finnen MJ, Lovell CR (1991) Purification and characterisation of phospholipase A2 from human epidermis. Biochem. Soc. Trans. 19:91S

    CAS  PubMed  Google Scholar 

  • Folch J, Lees M, Sloane-Stanley GH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem. 226:497–509

    CAS  PubMed  Google Scholar 

  • Gattaz WF, Hubner CK, Nevalainen TJ, Thuren T, Kinnunen PJK (1990) Increased serum phospholipase-A2 activity in schizophrenia: a replication study. Biol Psychiatry 28:495–501

    CAS  PubMed  Google Scholar 

  • Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM (2006) n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am. J. Clin. Nutr. 83(6 Suppl):1526S–1535S

    Google Scholar 

  • Horrobin DF (1999) The phospholipid concept of psychiatric disorders and its relationship to the neurodevelopmental concept of schizophrenia. In: Peet M, Glen I, Horrobin DF (eds) Phospholipid spectrum disorder in psychiatry. Marius, Lancashire, pp 3–20

    Google Scholar 

  • Horrobin DF, Jenkins K, Bennett CN, Christie WW (2002) Eicosapentaenoic acid and arachidonic acid: collaboration and not antagonism is the key to biological understanding. Prostagland Leurkotr Essent Fatty Acids 66:83–90

    Article  CAS  Google Scholar 

  • Khan MM, Evans DR, Gunna V, Scheffer RE, Parikh VV, Mahadik SP (2002) Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with antipsychotics. Schizophr. Res. 58:1–10

    Article  PubMed  Google Scholar 

  • Kemperman RF, Veurink M, van der Wal T, Knegtering H, Bruggeman R, Fokkema MR, Kema IP, Korf J, Muskiet FA (2006) Low essential fatty acid and B-vitamin status in a subgroup of patients with schizophrenia and its response to dietary supplementation. Prostaglandins Leukot Essent Fatty Acids. 74:75–85

    Article  CAS  PubMed  Google Scholar 

  • Kruger M, Langenhoven M, Faber M (1991) Fatty acid and amino acid composition tables. Supplement to MRC Food Composition Tables. MRC, Parow

    Google Scholar 

  • Levine J, Stahl Z, Sela BA, Ruderman V, Shumaico O, Babushkin I, Osher Y, Bersudsky Y, Belmaker RH (2006) Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry. 60:265–9

    Article  CAS  PubMed  Google Scholar 

  • McNamara RK, Able JA, Jandacek R, Rider T, Tso P (2009) Chronic risperidone treatment preferentially increases rat erythrocyte and prefrontal cortex omega-3 fatty acid composition: evidence for augmented biosynthesis. Schizophr Res. 107:150–157

    Article  PubMed  Google Scholar 

  • Mellor JE, Laugharne JDE, Peet M (1995) Schizophrenic symptoms and dietary intake of n-3 fatty acids. Schizophr. Res. 18:85–86

    Article  CAS  PubMed  Google Scholar 

  • Ohara K (2007) The n-3 polyunsaturated fatty acid/dopamine hypothesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 31:469–74

    Article  CAS  PubMed  Google Scholar 

  • Peet M, Brind J, Ramchand CN, Shah S, Vankar GK (2001) Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Schizophr. Res. 49:243–251

    Article  CAS  PubMed  Google Scholar 

  • Peet M, Shah S, Selvam K, Ramchand CN (2004) Polyunsaturated fatty acid levels in red cell membranes of unmedicated schizophrenic patients. World J Biol Psychiatry. 5:92–99

    Article  PubMed  Google Scholar 

  • Peet M (2008) Omega-3 polyunsaturated fatty acids in the treatment of schizophrenia. Isr J Psychiatry Relat Sci. 45:19–25

    PubMed  Google Scholar 

  • Puri BK, Ross BM, Treasaden IH (2008) Increased levels of ethane, a non-invasive, quantitative, direct marker of n-3 lipid peroxidation, in the breath of patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 32:858–862

    Article  CAS  PubMed  Google Scholar 

  • Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sitasawad S, Wagh UV, Debsikdar VB, Mahadik SP (2003) Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res. 121:109–122

    Article  CAS  PubMed  Google Scholar 

  • Reddy RD, Keshavan MS, Yao JK (2004) Reduced red blood cell membrane essential polyunsaturated fatty acids in first episode schizophrenia at neuroleptic-naive baseline. Schizophr Bull. 30:901–11

    PubMed  Google Scholar 

  • Sivrioglu EY, Kirli S, Sipahioglu D, Gursoy B, Sarandöl E (2007) The impact of omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: an open-label pilot study. Prog Neuropsychopharmacol Biol Psychiatry. 31:1493–1499

    Article  CAS  PubMed  Google Scholar 

  • Sumiyoshi T, Matsui M, Itoh H, Higuchi Y, Arai H, Takamiya C, Kurachi M (2008) Essential polyunsaturated fatty acids and social cognition in schizophrenia. Psychiatry Res. 157:87–93

    Article  CAS  PubMed  Google Scholar 

  • Vaddadi KS, Gilleard CJ, Soosai E, Polonowita AK, Gibson RA, Burrows GD (1996) Schizophrenia, tardive dyskinesia and essential fatty acids. Schizophr. Res. 20:287–294

    Article  CAS  PubMed  Google Scholar 

  • Van Jaarsveld PJ, Smuts CM, Tichelaar HY, Kruger M, Benadé AJS (2000) Effect of palm oil on plasma lipoprotein concentrations and plasma low-density lipoprotein composition in non-human primates. Int. J. Food Sci. Nutr. 51:S21–S30

    Article  PubMed  Google Scholar 

  • Von Hausswolff-Juhlin Y, Bjartveit M, Lindström E, Jones P (2009) Schizophrenia and physical health problems. Acta Psychiatr Scand Suppl 438:15–21

    Article  Google Scholar 

  • Yao JK, Leonard S, Reddy RD (2000) Membrane phospholipid abnormalities in postmortem brains from schizophrenic patients. Schizophr. Res. 42:7–17

    Article  CAS  PubMed  Google Scholar 

  • Yao JK, Stanley JA, Reddy RD, Keshavan MS, Pettegrew JW (2002) Correlations between peripheral polyunsaturated fatty acid content and in vivo membrane phospholipid metabolites. Biol. Psychiatry 52:823–830

    Article  CAS  PubMed  Google Scholar 

  • Yao JK, Magan S, Sonel AF, Gurklis JA, Sanders R, Reddy RD (2004) Effects of omega-3 fatty acid on platelet serotonin responsivity in patients with schizophrenia. Prostaglandins Leukot Essent Fatty Acids. 71:171–6

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge financial support by the Medical Research Council of South Africa, and technical assistance rendered by the staff of Stikland Hospital (especially Deanna Grobler and Sheena Price) and the Divisions of Chemical Pathology and Haematology, Tygerberg Hospital. The authors also wish to acknowledge the support and advice of the late Dr David Horrobin, and to thank Laxdale Ltd. for providing the EPA and placebo capsules for the trial. Thank you to Anne MacKenzie, Fiona Duffy and Lorraine McMullan for their participation.

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Authors and Affiliations

  1. Division of Chemical Pathology, National Health Laboratory Service, University of Stellenbosch, Stellenbosch, South Africa

    Susan J. van Rensburg

  2. Nutritional Intervention Research Unit, Medical Research Council, Parow, Centre of Excellence in Nutrition, North-West University, Potchefstroom, South Africa

    Cornelius M. Smuts

  3. Cape Peninsula University of Technology, Cape Town, South Africa

    Dinie Hon

  4. Centre for Statistical Consultation, University of Stellenbosch, Stellenbosch, South Africa

    Martin Kidd

  5. Division of Human Nutrition, University of Stellenbosch, Stellenbosch, South Africa

    Sulene van der Merwe

  6. Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa

    Christo Myburgh, Piet Oosthuizen & Robin Emsley

  7. Division of Chemical Pathology, Tygerberg Hospital, NHLS and University of Stellenbosch, P.O. Box 19113, Tygerberg, 7505, South Africa

    Susan J. van Rensburg

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  1. Susan J. van Rensburg
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  2. Cornelius M. Smuts
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  3. Dinie Hon
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  4. Martin Kidd
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  5. Sulene van der Merwe
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  6. Christo Myburgh
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  7. Piet Oosthuizen
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  8. Robin Emsley
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Correspondence to Susan J. van Rensburg.

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van Rensburg, S.J., Smuts, C.M., Hon, D. et al. Changes in erythrocyte membrane fatty acids during a clinical trial of eicosapentaenoic acid (EPA) supplementation in schizophrenia. Metab Brain Dis 24, 659–672 (2009). https://doi.org/10.1007/s11011-009-9160-7

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  • DOI: https://doi.org/10.1007/s11011-009-9160-7

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