Omega-3 fatty acids in schizophrenia Part II: Clinical applications


Ω-3 unsaturated fatty acids are compounds belonging to the group of essential fatty acids (EFAs). The history of the discovery of EFAs dates back to the 1930s of the twentieth century, however, growing interest in ω-3 EFAs in the context of mental health has been observed since the year 2000. In view of their multidirectional action, these compounds are a promising form of adjunctive therapy of many illnesses, including psychiatric disorders. The present article aims to review the literature on the clinical applicability of ω-3 EFAs in treating schizophrenia. We present the results of preclinical studies in this area and the mechanisms of ω-3 EFAs action discussed by the authors. The randomized controlled trials (RCTs) evaluating the possibility of using ω-3 EFAs in schizophrenia are characterized in detail. The results of the tests are not clear, which may result from the methodological diversity of interventions made. Ω-3 EFAs seem to be a promising form of adjunctive therapy of schizophrenia. Further research is needed, which will allow for defining groups of patients in which intervention will bring the expected results.

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  • 1. Nakamura M.T., Nara T.Y. Essential fatty acid synthesis and its regulation in mammals. Prostaglandins Leukot Essent Fatty Acids. 2003; 68(2): 145-50.

  • 2. Holman R.T. The slow discovery of the importance of omega 3 essential fatty acids in human health. J Nutr. 1998; 128(2): 427-433.

  • 3. Zeman M., Jirak R., Vecka M., Raboch J., Zak A. N-3 polyunsaturated fatty acids in psychiatric diseases: mechanisms and clinical data. Neuro Endocrinol Lett. 2012; 33(8): 736-48.

  • 4. Lorente-Cebrián S., Costa A.G., Navas-Carretero S., Zabala M., Martínez J.A., Moreno-Aliaga M.J. Role of omega-3 fatty acids in obesity, metabolic syndrome, and cardiovascular diseases: a review of the evidence. J Physiol Biochem. 2013; 69(3): 633-51..

  • 5. Eriksdotter M., Vedin I., Falahati F., Freund-Levi Y., Hjorth E., Faxen-Irving G., Wahlund L.O., Schultzberg M., Basun H., Cederholm T., Palmblad J.. Plasma Fatty Acid Profiles in Relation to Cognition and Gender in Alzheimer's Disease Patients During Oral Omega-3 Fatty Acid Supplementation: The OmegAD Study. J Alzheimers Dis. 2015; 48(3): 805-12.

  • 6. Dunstan J.A., Mori T.A., Barden A., Beilin L.J., Taylor A.L., Holt P.G., Prescott S.L. Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial. J Allergy Clin Immunol. 2003; 112(6): 1178-84.

  • 7. Gouveia T.L., Vieira de Sousa P.V., de Almeida S.S., Nejm M.B., Vieira de Brito J.M., Cysneiros R.M., de Brito M.V., Salu B.R., Oliva M.L., Scorza F.A., Naffah-Mazzacoratti Mda G.. High serum levels of proinflammatory markers during epileptogenesis. Can omega-3 fatty acid administration reduce this process? Epilepsy Behav. 2015; 51: 300-5.

  • 8. Farjadian S., Moghtaderi M., Kalani M., Gholami T., Hosseini Teshnizi S. Effects of omega-3 fatty acids on serum levels of T-helper cytokines in children with asthma. Cytokine. 2016; 85:61-6.

  • 9. Marcotte E.R., Pearson D.M., Srivastava L.K. Animal models of schizophrenia: a critical review. J Psychiatry Neurosci. 2001; 26(5): 395-410.

  • 10. Kilts C.D. The changing roles and targets for animal models of schizophrenia. Biol Psychiatry. 2001; 50(11): 845-55.

  • 11. Gama C.S., Canever L., Panizzutti B., Gubert C., Stertz L., Massuda R., Pedrini M., de Lucena D.F., Luca R.D., Fraga D.B., Heylmann A.S., Deroza P.F., Zugno A.I. Effects of omega-3 dietary supplement in prevention of positive, negative and cognitive symptoms: a study in adolescent rats with ketamine-induced model of schizophrenia. Schizophr Res. 2012; 141(2-3): 162-7.

  • 12. Zugno A.I., Chipindo H.L., Volpato A.M., Budni J., Steckert A.V., de Oliveira M.B., Heylmann A.S., da Rosa Silveira F., Mastella G.A., Maravai S.G., Wessler P.G., Binatti A.R., Panizzutti B., Schuck P.F., Quevedo J., Gama C.S. Omega-3 prevents behavior response and brain oxidative damage in the ketamine model of schizophrenia. Neuroscience. 2014; 259: 223-31.

  • 13. Zugno A.I., Chipindo H., Canever L., Budni J., Alves de Castro A., Bittencourt de Oliveira M., Heylmann A.S., Gomes Wessler P., da Rosa Silveira F., Damázio L.S., Mastella G.A., Kist L.W., Bogo M.R., Quevedo J., Gama C.S. Omega-3 fatty acids prevent the ketamine-induced increase in acetylcholinesterase activity in an animal model of schizophrenia. Life Sci. 2015; 121:65-9.

  • 14. Zugno A.I., Canever L., Mastella G., Heylmann A.S., Oliveira M.B., Steckert A.V., Castro A.A., dal Pizzol F., Quevedo J., Gama C.S.. Effects of omega-3 supplementation on interleukin and neurotrophin levels in an animal model of schizophrenia. An Acad Bras Cienc. 2015; 87 (2Suppl): 1475-86.

  • 15. El-Sayed El-Sisi A., Sokkar S.S., El-Sayed El-Sayad M., Sayed Ramadan E., Osman E.Y. Celecoxib and omega-3 fatty acids alone and in combination with risperidone affect the behavior and brain biochemistry in amphetamine-induced model of schizophrenia. Biomed Pharmacother. 2016; 82: 425-31.

  • 16. Watanabe T., Yamagata N., Takasaki K., Sano K., Hayakawa K., Katsurabayashi S., Egashira N., Mishima K., Iwasaki K., Fujiwara M. Decreased acetylcholine release is correlated to memory impairment in the Tg2576 transgenic mouse model of Alzheimer's disease. Brain Res. 2009; 1249: 222-8

  • 17. Micheau J., Marighetto A. Acetylcholine and memory: a long, complex and chaotic but still living relationship. Behav Brain Res. 2011; 221(2): 424-9.

  • 18. Potvin S., Stip E., Sepehry A.A., Gendron A., Bah R., Kouassi E. Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry. 2008; 63(8): 801-8.

  • 19. Fernandes B.S, Steiner J., Berk M., Molendijk M.L., Gonzalez-Pinto A., Turck C.W., Nardin P., Gonçalves C.A. Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: meta-analysis and implications. Mol Psychiatry. 2015; 20(9): 1108-19.

  • 20. Premack D. Human and animal cognition: continuity and discontinuity. Proc Natl Acad Sci U S A. 2007; 104(35): 13861-7.

  • 21. Amminger G.P., Schäfer M.R., Papageorgiou K., Klier C.M., Cotton S.M., Harrigan S.M., Mackinnon A., McGorry P.D., Berger G.E. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010; 67(2): 146-54.

  • 22. Pawelczyk T, Grancow-Grabka M, Kotlicka-Antczak M, Trafalska E, Pawełczyk A. A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia. J Psychiatr Res. 2016; 73: 34-44.

  • 23. Fenton W.S., Dickerson F., Boronow J., Hibbeln J.R., Knable M. A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry. 2001; 158(12): 2071-4.

  • 24. Peet M., Brind J., Ramchand C.N., Shah S., Vankar G.K. Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Schizophr Res. 2001; 49(3): 243-51.

  • 25. Emsley R., Myburgh C., Oosthuizen P., van Rensburg S.J. Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. Am J Psychiatry. 2002; 159(9): 1596-8

  • 26. Bentsen H., Osnes K., Refsum H., Solberg D.K., Bøhmer T. A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia. Transl Psychiatry. 2013; 3:e335.

  • 27. Jamilian H., Solhi H., Jamilian M. Randomized, placebo-controlled clinical trial of omega-3 as supplemental treatment in schizophrenia. Glob J Health Sci. 2014; 6(7): 103-8.

  • 28. Emsley R., Chiliza B., Asmal L., du Plessis S., Phahladira L., van Niekerk E., van Rensburg S.J., Harvey B.H. A randomized, controlled trial of omega-3 fatty acids plus an antioxidant for relapse prevention after antipsychotic discontinuation in first-episode schizophrenia. Schizophr Res. 2014; 158(1-3): 230-5.

  • 29. Peet M., Horrobin D.F.; E-E Multicentre Study Group. A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms. J Psychiatr Res. 2002; 36(1): 7-18.

  • 30. Lally J., Gallagher A., Bainbridge E., Avalos G., Ahmed M., McDonald C. Increases in triglyceride levels are associated with clinical response to clozapine treatment. J Psychopharmacol. 2013; 27(4):401-3.

  • 31. Joy C.B, Mumby-Croft R., Joy L.A. Polyunsaturated fatty acid supplementation for schizophrenia. Cochrane Database Syst Rev. 2006; (3):CD001257.

  • 32. Fusar-Poli P., Berger G. Eicosapentaenoic acid interventions in schizophrenia: meta-analysis of randomized, placebo-controlled studies. J Clin Psychopharmacol. 2012; 32(2): 179-85.

  • 33. Amminger G.P., Schäfer M.R., Schlögelhofer M., Klier C.M., McGorry P.D. Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study. Nat Commun. 2015; 6:7934.


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