Rola wielonienasyconych kwasów tłuszczowych omega-3 w etiopatogenezie i leczeniu zaburzeń psychicznych

• Authors: Tomasz Pawełczyk , Magdalena Kotlicka-Antczak , Anna Dietrich-Muszalska , Magdalena Grygo , Kamila Krawczyk , Tomasz Wolańczyk , Janusz Rybakowski , Jolanta Rabe-Jabłońska

Title variants

EN

Role of omega-3 polyunsaturated fatty acids in the pathogenesis and treatment of mental disorders

• Languages of publication: EN PL

Abstracts

EN

Polyunsaturated fatty acids (PUFA), omega-3 are essential for normal development and function of the central nervous system. They are an essential structural component of neuronal cell membranes and are a source of biologically active substances, which perform complex functions, and participate in signal transmission within cells. Disorders of lipid metabolism and FFA are observed in the course of many disorders and mental illness, i.e. schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, autism. Those disturbances are genetically based and contribute along with other abnormalities to increased vulnerability to particular disorder’s symptoms development. In addition, the diet of most residents of European countries does not provide enough omega-3 PUFAs, which are exogenous substances, i.e. not synthesized in sufficient quantities in the human body. Moreover, in the course of many mental disorders an excessive loss of long-chain PUFA through excitotoxicity processes and oxidative stress is observed, which further contributes to depletion of the available pool of PUFAs. In the case of schizophrenia, numerous experimental and clinical studies have led researchers to formulate hypotheses explaining the development of this disease based on the presence of lipid metabolism dysfunctions. The paper presents a review of recent literature and results of the original research conducted by the authors dealing with PUFAs metabolism disturbances in patients with mental disorders listed above.

PL

Wielonienasycone kwasy tłuszczowe (WKT) omega-3 są niezbędne do prawidłowego rozwoju i funkcji ośrodkowego układu nerwowego. Stanowią istotny element strukturalny neuronalnych błon komórkowych oraz są źródłem aktywnych biologicznie substancji, które pełnią złożone funkcje sygnałowe oraz uczestniczą w przekazywaniu informacji wewnątrz komórek. Zaburzenia metabolizmu lipidów i WKT obserwuje się w przebiegu wielu zaburzeń i chorób psychicznych: schizofrenii, zaburzeń afektywnych, zespołu nadpobudliwości psychoruchowej z deficytem uwagi, autyzmu i innych. Dysfunkcje te mają podłoże genetyczne i wraz z innymi nieprawidłowościami przyczyniają się do zwiększenia podatności na wystąpienie objawów psychopatologicznych danego zaburzenia. Ponadto dieta mieszkańców większości krajów europejskich nie zapewnia wystarczającej ilości WKT omega-3, które należą do substancji egzogennych, tj. niesyntetyzowanych w wystarczającej ilości w organizmie ludzkim. Co więcej, w przebiegu wielu zaburzeń psychicznych dochodzi do nadmiernej utraty długołańcuchowych WKT za pośrednictwem procesów ekscytotoksyczności i stresu oksydacyjnego, co dalej przyczynia się do uszczuplenia dostępnej puli WKT. W przypadku schizofrenii liczne badania eksperymentalne i kliniczne doprowadziły badaczy do sformułowania hipotezy wyjaśniającej rozwój tej choroby w oparciu o występowanie dysfunkcji metabolizmu lipidów. W pracy przedstawiono przegląd aktualnego piśmiennictwa oraz wyniki oryginalnych badań przeprowadzonych przez autorów zajmujących się problematyką zaburzeń metabolizmu WKT u chorych z wymienionymi wyżej zaburzeniami psychicznymi.

Keywords

EN

aetiology; etiologia; mood disorders; polyunsaturated fatty acids; schizofrenia; schizophrenia; terapia; therapeutics; wielonienasycone kwasy tłuszczowe; zaburzenia nastroju

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Pediatria i Medycyna Rodzinna
• Year: 2010
• Volume: 6
• Issue: 4
• Pages: 333-344

Contributors

author

Tomasz Pawełczyk

• Klinika Zaburzeń Afektywnych i Psychotycznych Uniwersytetu Medycznego w Łodzi

author

Magdalena Kotlicka-Antczak

• Klinika Zaburzeń Afektywnych i Psychotycznych Uniwersytetu Medycznego w Łodzi

author

Anna Dietrich-Muszalska

• Klinika Zaburzeń Afektywnych i Psychotycznych Uniwersytetu Medycznego w Łodzi

author

Magdalena Grygo

• Oddział Psychiatrii Wieku Rozwojowego, Samodzielny Publiczny Dziecięcy Szpital Kliniczny w Warszawie

author

Kamila Krawczyk

• Klinika Psychiatrii Dorosłych Uniwersytetu im. Karola Marcinkowskiego w Poznaniu

author

Tomasz Wolańczyk

• Klinika Psychiatrii Wieku Rozwojowego Warszawskiego Uniwersytetu Medycznego

author

Janusz Rybakowski

• Klinika Psychiatrii Dorosłych Uniwersytetu im. Karola Marcinkowskiego w Poznaniu

author

Jolanta Rabe-Jabłońska

References

• 1. Makrides M., Smithers L.G., Gibson R.A.: Role of long-chain polyunsaturated fatty acids in neurodevelopment and growth. Nestle Nutr. Workshop Ser. Pediatr. Program. 2010; 65: 123-133; discussion 133-136.
• 2. Mourek J., Langmeier M., Pokorny J.: Significance of the plasma membrane for the nerve cell function, development and plasticity. Neuro Endocrinol. Lett. 2009; 30: 694-699.
• 3. Bazan N.G.: Cellular and molecular events mediated by docosahexaenoic acid-derived neuroprotectin D1 signaling in photoreceptor cell survival and brain protection. Prostaglandins Leukot. Essent. Fatty Acids 2009; 81: 205-211.
• 4. Michailidis I.E., Zhang Y., Yang J.: The lipid connec-tion-regulation of voltage-gated Ca2+ channels by phos-phoinositides. Pflugers Arch. 2007; 455: 147-155.
• 5. De Petrocellis L., Di Marzo V: An introduction to the endocannabinoid system: from the early to the latest concepts. Best Pract. Res. Clin. Endocrinol. Metab. 2009; 23: 1-15.
• 6. Haeggstrom J.Z., Rinaldo-Matthis A., Wheelock C.E., Wetterholm A.: Advances in eicosanoid research, novel therapeutic implications. Biochem. Biophys. Res. Commun. 2010; 396: 135-139.
• 7. Bazan N.G.: Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer’s disease. J. Lipid Res. 2009; 50 supl.: S400-S405.
• 8. McNamara R.K., Carlson S.E.: Role of omega-3 fatty acids in brain development and function: potential implications for the pathogenesis and prevention of psychopathology. Prostaglandins Leukot. Essent. Fatty Acids 2006; 75: 329-349.
• 9. Freeman M.P.: Omega-3 fatty acids in major depressive disorder. J. Clin. Psychiatry 2009; 70 supl. 5: 7-11.
• 10. Peet M.: Omega-3 polyunsaturated fatty acids in the treatment of schizophrenia. Isr. J. Psychiatry Relat. Sci. 2008; 45: 19-25.
• 11. Raz R., Gabis L.: Essential fatty acids and attention-deficit-hyperactivity disorder: a systematic review. Dev. Med. Child Neurol. 2009; 51: 580-592.
• 12. Schuchardt J.P., Huss M., Stauss-Grabo M., Hahn A.: Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children. Eur. J. Pediatr. 2010; 169: 149-164.
• 13. Appleton K.M., Rogers P.J., Ness A.R.: Is there a role for n-3 long-chain polyunsaturated fatty acids in the regulation of mood and behaviour? A review of the evidence to date from epidemiological studies, clinical studies and intervention trials. Nutr. Res. Rev. 2008; 21: 13-41.
• 14. Horrobin D.: The Madness of Adam and Eve: How Schizophrenia Shaped Humanity. Bantam Press, London 2001.
• 15. Horrobin D.F., Manku M.S.: Possible role of prostaglandin E1 in the affective disorders and in alcoholism. Br. Med. J. 1980; 280: 1363-1366.
• 16. Morrow J.D., Awad J.A., Oates J.A., Roberts L.J. 2nd: 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.
• 17. Smesny S., Klemm S., Stockebrand M. i wsp.: Endophenotype properties of niacin sensitivity as marker of impaired prostaglandin signalling in schizophrenia. Prostaglandins Leukot. Essent. Fatty Acids 2007; 77: 79-85.
• 18. Ward P.E., Sutherland J., Glen E.M., Glen A.I.: Niacin skin flush in schizophrenia: a preliminary report. Schizophr. Res. 1998; 29: 269-274.
• 19. Fiedler P., Wolkin A., Rotrosen J.: Niacin-induced flush as a measure of prostaglandin activity in alcoholics and schizophrenics. Biol. Psychiatry 1986; 21: 1347-1350.
• 20. Rybakowski J., Weterle R.: Niacin test in schizophrenia and affective illness. Biol. Psychiatry 1991; 29: 834-836.
• 21. Kerr M., Cotton S., Proffitt T. i wsp.: The topical niacin sensitivity test: an inter- and intra-rater reliability study in healthy controls. Prostaglandins Leukot. Essent. Fatty Acids 2008; 79: 15-19.
• 22. Smesny S., Berger G., Rosburg T. i wsp.: Potential use of the topical niacin skin test in early psychosis - a combined approach using optical reflection spectroscopy and a descriptive rating scale. J. Psychiatr. Res. 2003; 37: 237-247.
• 23. Glen A.I., Cooper S.J., Rybakowski J. i wsp.: Membrane fatty acids, niacin flushing and clinical parameters. Prostaglandins Leukot. Essent. Fatty Acids 1996; 55: 9-15.
• 24. Wilson D.W, Douglass A.B.: Niacin skin flush is not diagnostic of schizophrenia. Biol. Psychiatry 1986; 21: 974-977.
• 25. Smesny S., Kinder D., Willhardt I. i wsp.: Increased calcium-independent phospholipase A2 activity in first but not in multiepisode chronic schizophrenia. Biol. Psychiatry 2005; 57: 399-405.
• 26. Ross B.M., Turenne S., Moszczynska A. i wsp.: Differential alteration of phospholipase A2 activities in brain of patients with schizophrenia. Brain Res. 1999; 821: 407-413.
• 27. Pettegrew J.W., Keshavan M.S., Panchalingam K. i wsp.: Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drug-naive 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.
• 28. Reddy R., Keshavan M.S.: Phosphorus magnetic resonance spectroscopy: its utility in examining the membrane hypothesis of schizophrenia. Prostaglandins Leu-kot. Essent. Fatty Acids 2003; 69: 401-405.
• 29. Tavares H., Yacubian J., Talib L.L. i wsp.: Increased phospholipase A2 activity in schizophrenia with absent response to niacin. Schizophr. Res. 2003; 61: 1-6.
• 30. Hudson C.J., Kennedy J.L., Gotowiec A. i wsp.: Genetic variant near cytosolic phospholipase A2 associated with schizophrenia. Schizophr. Res. 1996; 21: 111-116.
• 31. Liu Y., Zhang H., Ju G. i wsp.: A study of the PEMT gene in schizophrenia. Neurosci. Lett. 2007; 424: 203-206.
• 32. Gysin R., Kraftsik R., Sandell J. i wsp.: Impaired glutathione synthesis in schizophrenia: convergent genetic and functional evidence. Proc. Natl Acad. Sci. USA 2007; 104: 16621-16626.
• 33. Le Hellard S., M^eisen T.W, Djurovic S. i wsp.: Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples. Mol. Psychiatry 2010; 15: 463-472.
• 34. Rybakowski J.K., Borkowska A., Czerski P.M. i wsp.: The study of cytosolic phospholipase A2 gene polymorphism in schizophrenia using eye movement disturbances as an endophenotypic marker. Neuropsychobiology 2003; 47: 115-119.
• 35. Barbosa N.R., Junqueira R.M., Vallada H.P., Gattaz WF.: Association between BanI genotype and increased phospholipase A2 activity in schizophrenia. Eur. Arch. Psychiatry Clin. Neurosci. 2007; 257: 340-343.
• 36. Ohara K.: The n-3 polyunsaturated fatty acid/dopamine hypothesis of schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry 2007; 31: 469-474.
• 37. Bartosz G.: Druga twarz tlenu. Wolne rodniki w przyrodzie. Wydawnictwo Naukowe PWN, Warszawa 2003.
• 38. McConnell E.J., Bittelmeyer A.M., Raess B.U.: Irreversible inhibition of plasma membrane (Ca2+ + Mg2+)-ATPase and Ca2+ transport by 4-OH-2,3-?r<ms-nonenal. Arch. Biochem. Biophys. 1999; 361: 252-256.
• 39. Horrobin D.F., Manku M.S., Hillman H. i wsp.: Fatty acid levels in the brains of schizophrenics and normal controls. Biol. Psychiatry 1991; 30: 795-805.
• 40. Dietrich-Muszalska A., Olas B., Rabe-Jablonska J.: Oxidative stress in blood platelets from schizophrenic patients. Platelets 2005; 16: 386-391.
• 41. Keshavan M.S., Mallinger A.G., Pettegrew J.W, Dippold C.: Erythrocyte membrane phospholipids in psychotic patients. Psychiatry Res. 1993; 49: 89-95.
• 42. Mahadik S.P., Sitasawad S., Mulchandani M.: Membrane peroxidation and the neuropathology of schizophrenia. W: Peet M., Glen I., Horrobin D.F. (red.): Phospholipid Spectrum Disorder in Psychiatry. Marius Press, Carnforth 1999: 99-111.
• 43. Reddy R.D., Yao J.K.: Free radical pathology in schizophrenia: a review. Prostaglandins Leukot. Essent. Fatty Acids 1996; 55: 33-43.
• 44. Yao J.K., Reddy R., van Kammen D.P.: Abnormal age-related changes of plasma antioxidant proteins in schizophrenia. Psychiatry Res. 2000; 97: 137-151.
• 45. Mahadik S.P., Mukherjee S.: Free radical pathology and antioxidant defense in schizophrenia: a review. Schizophr. Res. 1996; 19: 1-17.
• 46. Yao J.K., Reddy R.D., van Kammen D.P.: Oxidative damage and schizophrenia: an overview of the evidence and its therapeutic implications. CNS Drugs 2001; 15: 287-310.
• 47. Zhang X.Y., Tan Y.L., Cao L.Y. i wsp.: Antioxidant enzymes and lipid peroxidation in different forms of schizophrenia treated with typical and atypical anti-psychotics. Schizophr. Res. 2006; 81: 291-300.
• 48. Delanty N., Dichter M.A.: Oxidative injury in the nervous system. Acta Neurol. Scand. 1998; 98: 145-153.
• 49. Akyol O., Herken H., Uz E. i wsp.: The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. The possible role of oxidant/ antioxidant imbalance. Prog. Neuropsychopharmacol. Biol. Psychiatry 2002; 26: 995-1005.
• 50. Herken H., Uz E., Ozyurt H. i wsp.: Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia. Mol. Psychiatry 2001; 6: 66-73.
• 51. Khan M.M., Evans D.R., Gunna V i wsp.: 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. 2002; 58: 1-10.
• 52. Khan N.S., Das I.: Oxidative stress and superoxide dis-mutase in schizophrenia. Biochem. Soc. Trans. 1997; 25: 418S.
• 53. Lohr J.B., Kuczenski R., Bracha H.S. i wsp.: Increased indices of free radical activity in the cerebrospinal fluid of patients with tardive dyskinesia. Biol. Psychiatry 1990; 28: 535-539.
• 54. Mahadik S.P., Mukherjee S., Scheffer R. i wsp.: Elevated plasma lipid peroxides at the onset of nonaffective psychosis. Biol. Psychiatry 1998; 43: 674-679.
• 55. McCreadie R.G., MacDonald E., Wiles D. i wsp.: The Nithsdale Schizophrenia Surveys. XIV: Plasma lipid peroxide and serum vitamin E levels in patients with and without tardive dyskinesia, and in normal subjects. Br. J. Psychiatry 1995; 167: 610-617.
• 56. Dalla Libera A., Scutari G., Boscolo R. i wsp.: Antioxidant properties of clozapine and related neuroleptics. Free Radic. Res. 1998; 29: 151-157.
• 57. Dietrich-Muszalska A.: Wpływ działania haloperidolu na peroksydację lipidów w ludzkich płytkach krwi i osoczu w badaniach in vitro. Psychiatr. Psychol. Klin. 2004; 4: 150-156.
• 58. Dietrich-Muszalska A., Rabe-Jabłońska J., Zgirski A.: Wpływ działania olanzapiny (Zolafren) na peroksydację lipidów w ludzkich płytkach krwi i osoczu w układzie in vitro. Psychiatr. Psychol. Klin. 2004; 4: 13-19.
• 59. Fischer V, Haar J.A., Greiner L. i wsp.: Possible role of free radical formation in clozapine (Clozaril)-induced agranulocytosis. Mol. Pharmacol. 1991; 40: 846-853.
• 60. Kropp S., Kern V, Lange K. i wsp.: Oxidative stress during treatment with first- and second-generation antipsychotics. J. Neuropsychiatry Clin. Neurosci. 2005; 17: 227-231.
• 61. Dietrich-Muszalska A., Rabe-Jabłońska J., Olas B.: The effects of the second generation antipsychotics and a typical neuroleptic on collagen-induced platelet aggregation in vitro. World J. Biol. Psychiatry 2010; 11: 293-299.
• 62. Weissman M.M., Bland R.C., Canino G.J. i wsp.: Cross-national epidemiology of major depression and bipolar disorder. JAMA 1996; 276: 293-299.
• 63. Hibbeln J.R.: Fish consumption and major depression. Lancet 1998; 351: 1213.
• 64. Maes M., Christophe A., Delanghe J. i wsp.: Lowered ω3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res. 1999; 85: 275-291.
• 65. Maes M., Smith R., Christophe A. i wsp.: Fatty acid composition in major depression: decreased ω3 fractions in cholesteryl esters and increased C20:4o6/ C20:5o3 ratio in cholesteryl esters and phospholipids. J. Affect. Disord. 1996; 38: 35-46.
• 66. Adams P.B., Lawson S., Sanigorski A., Sinclair A.J.: Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids 1996; 31 supl.: S157-S161.
• 67. Edwards R., Peet M., Shay J., Horrobin D.: Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J. Affect. Disord. 1998; 48: 149-155.
• 68. Peet M., Murphy B., Shay J., Horrobin D.: Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol. Psychiatry 1998; 43: 315-319.
• 69. Tiemeier H., van Tuijl H.R., Hofman A. i wsp.: Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study. Am. J. Clin. Nutr. 2003; 78: 40-46.
• 70. Maes M., Smith R., Scharpe S.: The monocyte-T-lymphocyte hypothesis of major depression. Psychoneuroendocrinology 1995; 20: 111-116.
• 71. Smith R.S.: The macrophage theory of depression. Med. Hypotheses 1991; 35: 298-306.
• 72. Lieb J., Karmali R., Horrobin D.: Elevated levels of prostaglandin E2 and thromboxane B2 in depression. Prostaglandins Leukot. Med. 1983; 10: 361-367.
• 73. Song C., Lin A., Bonaccorso S. i wsp.: The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression. J. Affect. Disord. 1998; 49: 211-219.
• 74. Hibbeln J.R., Salem N. Jr: Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Am. J. Clin. Nutr. 1995; 62: 1-9.
• 75. Hibbeln J.R., Linnoila M., Umhau J.C. i wsp.: Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics. Biol. Psychiatry 1998; 44: 235-242.
• 76. Hibbeln J.R., Salem N. Jr: Omega-3 Fatty Acids and Psychiatric Disorders. Humana Press, Inc., Totowa, NJ 2001.
• 77. Delion S., Chalon S., Herault J. i wsp.: Chronic dietary α-linolenic acid deficiency alters dopaminergic and serotoninergic neurotransmission in rats. J. Nutr. 1994; 124: 2466-2476.
• 78. Kodas E., Galineau L., Bodard S. i wsp.: Serotoninergic neurotransmission is affected by n-3 polyunsaturated fatty acids in the rat. J. Neurochem. 2004; 89: 695-702.
• 79. Hibbeln J.R., Umhau J.C., George D.T., Salem N. Jr: Do plasma polyunsaturates predict hostility and depression? World Rev. Nutr. Diet. 1997; 82: 175-186.
• 80. Horrobin D.F., Bennett C.N.: Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, ageing and osteoporosis. Possible candidate genes. Prostaglandins Leukot. Essent. Fatty Acids 1999; 60: 217-234.
• 81. Leviel V, Naquet R.: A study of the action of valproic acid on the kindling effect. Epilepsia 1977; 18: 229-234.
• 82. Sanders-Bush E., Tsutsumi M., Burris K.D.: Serotonin receptors and phosphatidylinositol turnover. Ann. N. Y. Acad. Sci. 1990; 600: 224-235; discussion 235-236.
• 83. Yehuda S., Carasso R.L., Mostofsky D.I.: Essential fatty acid preparation (SR-3) raises the seizure threshold in rats. Eur. J. Pharmacol. 1994; 254: 193-198.
• 84. Dubovsky S.L., Thomas M., Hijazi A., Murphy J.: Intracellular calcium signalling in peripheral cells of patients with bipolar affective disorder. Eur. Arch. Psychiatry Clin. Neurosci. 1994; 243: 229-234.
• 85. Filuś J., Rybakowski J.: Czynniki neurotrofowe i ich rola w patogenezie chorób afektywnych. Psychiatr. Pol. 2005; 39: 883-897.
• 86. Krawczyk K., Rybakowski J.: Korzystne efekty dodania kwasów tłuszczowych omega-3 do leczenia przeciwdepresyjnego w depresji lekoopornej - badanie wstępne. Farmakoter. Psych. Neurol. 2008; 24: 149-153.
• 87. Amani R.: Is dietary pattern of schizophrenia patients different from healthy subjects? BMC Psychiatry 2007; 7: 15.
• 88. McNamara R.K., Jandacek R, Rider T. i wsp.: Abnormalities in the fatty acid composition of the postmortem orbitofrontal cortex of schizophrenic patients: gender differences and partial normalization with antipsychotic medications. Schizophr. Res. 2007; 91: 37-50.
• 89. Peet M.: Nutrition and schizophrenia: beyond omega-3 fatty acids. Prostaglandins Leukot. Essent. Fatty Acids 2004; 70: 417-422.
• 90. 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: 1596-1598.
• 91. Peet M., Brind J., Ramchand C.N. i wsp.: Two doubleblind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Schizophr. Res. 2001; 49: 243-251.
• 92. Peet M., Horrobin D.F.; E-E Multicentre Study Group: A dose-ranging exploratory study of the effects of ethyleicosapentaenoate in patients with persistent schizophrenic symptoms. J. Psychiatr. Res. 2002; 36: 7-18.
• 93. Berger G.E., Proffitt TM., McConchie M. i wsp.: Ethyleicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial. J. Clin. Psychiatry 2007; 68: 1867-1875.
• 94. Richardson A.J., Easton T, Puri B.K.: Red cell and plasma fatty acid changes accompanying symptom remission in a patient with schizophrenia treated with eicosapentaenoic acid. Eur. Neuropsychopharmacol. 2000; 10: 189-193.
• 95. Emsley R., Niehaus D.J., Koen L. i wsp.: The effects of eicosapentaenoic acid in tardive dyskinesia: a randomized, placebo-controlled trial. Schizophr. Res. 2006; 84: 112-120.
• 96. Fenton WS., Dickerson F., Boronow J. i wsp.: 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: 2071-2074.
• 97. Joy C.B., Mumby-Croft R., Joy L.A.: Polyunsaturated fatty acid supplementation for schizophrenia. Cochrane Database Syst. Rev. 2006; 3: CD001257.
• 98. Freeman M.P., Hibbeln J.R., Wisner K.L. i wsp.: Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J. Clin. Psychiatry 2006; 67: 1954-1967.
• 99. Sumiyoshi T., Matsui M., Itoh H. i wsp.: Essential polyunsaturated fatty acids and social cognition in schizophrenia. Psychiatry Res. 2008; 157: 87-93.
• 100. Marik P.E., Varon J.: Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin. Cardiol. 2009; 32: 365-372.
• 101. Amminger G.P., Schafer M.R., Papageorgiou K. i wsp.: Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch. Gen. Psychiatry 2010; 67: 146-154.
• 102. McGorry P.D., Nelson B., Amminger G.P. i wsp.: Intervention in individuals at ultra-high risk for psychosis: a review and future directions. J. Clin. Psychiatry 2009; 70: 1206-1212.
• 103. Burgess J.R., Stevens L., Zhang W, Peck L.: Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am. J. Clin. Nutr. 2000; 71 (1 supl.): 327S-330S.
• 104. Chen J.R., Hsu S.F., Hsu C.D. i wsp.: Dietary patterns and blood fatty acid composition in children with attention-deficit hyperactivity disorder in Taiwan. J. Nutr. Bio-chem. 2004; 15: 467-472.
• 105. Mitchell E.A., Aman M.G., Turbott S.H., Manku M.: Clinical characteristics and serum essential fatty acid levels in hyperactive children. Clin. Pediatr. (Phila.) 1987; 26: 406-411.
• 106. Stevens L.J., Zentall S.S., Abate M.L. i wsp.: Omega-3 fatty acids in boys with behavior, learning, and health problems. Physiol. Behav. 1996; 59: 915-920.
• 107. Stevens L.J., Zentall S.S., Deck J.L. i wsp.: Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am. J. Clin. Nutr. 1995; 62: 761-768.
• 108. Bell J.G., MacKinlay E.E., Dick J.R i wsp.: Essential fatty acids and phospholipase A2 in autistic spectrum disorders. Prostaglandins Leukot. Essent. Fatty Acids 2004; 71: 201-204.
• 109. Meguid N.A., Atta H.M., Gouda A.S., Khalil R.O.: Role of polyunsaturated fatty acids in the management of Egyptian children with autism. Clin. Biochem. 2008; 41: 1044-1048.
• 110. Vancassel S., Durand G., Barthelemy C. i wsp.: Plasma fatty acid levels in autistic children. Prostaglandins Leukot. Essent. Fatty Acids 2001; 65: 1-7.
• 111. Bu B., Ashwood P., Harvey D. i wsp.: Fatty acid compositions of red blood cell phospholipids in children with autism. Prostaglandins Leukot. Essent. Fatty Acids 2006; 74: 215-221.
• 112. Voigt R.G., Llorente A.M., Jensen C.L. i wsp.: A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder. J. Pediatr. 2001; 139: 189-196.
• 113. Richardson A.J., Puri B.K.: A randomized double-blind, placebo-controlled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties. Prog. Neuropsychopharmacol. Biol. Psychiatry 2002; 26: 233-239.
• 114. Stevens L., Zhang W, Peck L. i wsp.: EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. Lipids 2003; 38: 1007-1021.
• 115. Richardson A.J., Montgomery P.: The Oxford-Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder. Pediatrics 2005; 115: 1360-1366.
• 116. Sinn N., Bryan J.: Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behavior problems associated with child ADHD. J. Dev. Behav. Pediatr. 2007; 28: 82-91.
• 117. Johnson M., Ostlund S., Fransson G. i wsp.: Omega-3/ omega-6 fatty acids for attention deficit hyperactivity disorder: a randomized placebo-controlled trial in children and adolescents. J. Atten. Disord. 2009; 12: 394-401.
• 118. Amminger G.P., Berger G.E., Schafer M.R. i wsp.: Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Biol. Psychiatry 2007; 61: 551-553.
• 119. Meiri G., Bichovsky Y., Belmaker R.H.: Omega 3 fatty acid treatment in autism. J. Child Adolesc. Psychopharmacol. 2009; 19: 449-451.
• 120. Politi P., Cena H., Comelli M. i wsp.: Behavioral effects of omega-3 fatty acid supplementation in young adults with severe autism: an open label study. Arch. Med. Res. 2008; 39: 682-685.
• 121. Patrick L., Salik R.: The effect of essential fatty acid supplementation on language development and learning skills in autism and Asperger’s syndrome. Autism Asperger’s Digest Magazine 2005; (1): 36-37.

• Document Type: article