Majör Depresif Bozukluk ve Omega 3 Yağ Asitleri

Öz

Bu derlemenin amacı, omega 3 yağ asitleri ile majör depresif bozukluk arasındaki ilişkiye genel bir bakış sunmaktır. Majör depresif bozukluk, dünya çapında 280 milyon insanı etkileyen yaygın bir mental bozukluktur ve etiyolojisi tam olarak belli değildir. Majör depresif bozukluğu olan bireylerde, eritrosit membranlarında veya plazma fosfolipitlerinde düşük eikosapentaenoik asit + dokosaheksaenoik asit seviyeleri görülmektedir. Bu nedenle, eritrosit membranlarında ve diyette omega 3 yağ asitleri, özellikle eikosapentaenoik asit ve dokosaheksaenoik asit eksikliği ile majör depresif bozukluğun etiyolojisi ve patofizyolojisi arasında olası bir ilişki olduğu kabul edilmektedir. Son yıllarda omega-3 yağ asitleri, merkezi sinir sistemi üzerindeki potansiyel antidepresan etkileri nedeniyle depresyon tedavisinde dikkat çekmektedir. Bazı çalışmalar, omega-3 takviyesi sonrasında depresif semptomlarda anlamlı azalmalar bildirirken, diğer çalışmalar bu etkileri doğrulamamıştır. Bu tutarsız bulgular, çalışma tasarımlarındaki farklılıklardan veya bireysel faktörlerden kaynaklanabilir. Ancak omega-3 takviyeleri genel olarak güvenli kabul edilmekte ve standart antidepresan tedavisine ek olarak kullanılabilecekleri düşünülmektedir. Bu alanda, daha geniş örneklem gruplarıyla ve tutarlı çalışma tasarımlarıyla yapılacak ileri araştırmalara ihtiyaç vardır.

Anahtar Kelimeler

• balık yağı
• DHA
• EPA
• majör depresif bozukluk
• omega 3 yağ asitleri

Major Depressive Disorder and Omega 3 Fatty Acids

Öz

This review aims to offer an overview of the correlation between omega 3 fatty acids and major depressive disorder. Major depressive disorder is a common mental disorder that affects 280 million people worldwide and its etiology is not entirely clear. In individuals with major depressive disorder, low levels of eicosapentaenoic acid + docosahexaenoic acid in erythrocyte membranes or plasma phospholipids is seen. This is why a possible correlation between the deficiency of omega 3 fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid, in erythrocyte membranes and diet and the etiology and pathophysiology of major depressive disorder has been accepted. In recent years, omega-3 fatty acids have gained attention in depression treatment due to their potential antidepressant effects on the central nervous system. While some studies have reported significant reductions in depressive symptoms following omega-3 supplementation, other studies have not confirmed these effects. These inconsistent findings may be due to differences in study designs or individual factors. However, omega-3 supplements are generally considered safe and can be used as an adjunct to standard antidepressant treatment. Further research in this area with larger sample sizes and consistent study designs is needed.

Anahtar Kelimeler

• fish oil
• DHA
• EPA
• major depressive disorder
• omega 3 fatty acids

Kaynakça

1. 1. Bang HO, Dyerberg J. Plasma lipids and lipoproteins in Greenlandic West Coast Eskimos. Acta Med Scand. 1972;192(1-2):85-94. doi: 10.1111/j.0954- 6820.1972.tb04782.x. 2. Chiu C, Huang S, Su K, Lu M, Huang M, Chen C, et al. Polyunsaturated fatty acid deficit in patients with bipolar mania. Eur Neuropsychopharmacol. 2003;13(2):99-103. doi: 10.1016/s0924-977x(02)00130-x. 3. Green P, Hermesh H, Monselise A, Marom S, Presburger G, Weizman A. Red cell membrane omega-3 fatty acids are decreased in nondepressed patients with social anxiety disorder. Eur Neuropsychopharmacol. 2006;16(2):107-13. doi: 10.1016/j.euroneuro.2005.07.005.
2. 4. Patrick RP, Ames BN. Vitamin D and the omega‐3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. FASEB J. 2015;29(6):2207-22. doi: 10.1096/fj.14- 268342. 5. McNamara RK. Role of omega-3 fatty acids in the etiology, treatment, and prevention of depression: current status and future directions. J Nutr Intermed Metab. 2016;5:96-106. doi: 10.1016/j.jnim.2016.04.004. 6. Wani AL, Bhat SA, Ara A. Omega-3 fatty acids and the treatment of depression: a review of scientific evidence. Integr Med Res. 2015;4(3):132-41. doi: 10.1016/j.imr.2015.07.003. 7. Sontrop J, Campbell MK. ω-3 polyunsaturated fatty acids and depression: a review of the evidence and a methodological critique. Prev Med. 2006;42(1):4-13. doi: 10.1016/j.ypmed.2005.11.005.
3. 8. Kang J, Gleason E. Omega-3 fatty acids and hippocampal neurogenesis in depression. CNS Neurol Disord Drug Targets. 2013;12(4):460-5. doi: 10.2174/1871527311312040004. 9. Caraci F, Copani A, Nicoletti F, Drago F. Depression and Alzheimer's disease: neurobiological links and common pharmacological targets. Eur J Pharmacol. 2010;626(1):64- 71. doi: 10.1016/j.ejphar.2009.10.022. 10. Huffman JC, Celano CM, Beach SR, Motiwala SR, Januzzi JL. Depression and cardiac disease: epidemiology, mechanisms, and diagnosis. Cardiovasc Psychiatry Neurol. 2013;2013:695925. doi: 10.1155/2013/695925.
4. 11. Maes M, Yirmyia R, Noraberg J, Brene S, Hibbeln J, Perini G, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009;24(1):27-53. doi: 10.1007/s11011-008-9118-1. 12. Parletta N, Milte CM, Meyer BJ. Nutritional modulation of cognitive function and mental health. J Nutr Biochem. 2013;24(5):725-43. doi: 10.1016/j.jnutbio.2013.01.002.
5. 13. Deacon G, Kettle C, Hayes D, Dennis C, Tucci J. Omega 3 polyunsaturated fatty acids and the treatment of depression. Crit Rev Food Sci Nutr. 2017;57(1):212-3. doi: 10.1080/10408398.2013.876959. 14. Frasure-Smith N, Lespérance F, Julien P. Major depression is associated with lower omega-3 fatty acid levels in patients with recent acute coronary syndromes. Biol Psychiatry. 2004;55(9):891-6. doi: 10.1016/j.biopsych.2004.01.021. 15. Surette ME. The science behind dietary omega-3 fatty acids. CMAJ. 2008;178(2):177-80. doi: 10.1503/cmaj.071356.
6. 16. Saini RK, Prasad P, Sreedhar RV, Akhilender Naidu K, Shang X, Keum Y. Omega−3 polyunsaturated fatty acids (PUFAs): emerging plant and microbial sources, oxidative stability, bioavailability, and health benefits—a review. Antioxidants. 2021;10(10):1627. doi: 10.3390/antiox10101627.
7. 17. Konukoğlu D. Omega-3 ve omega-6 yağ asitlerinin özellikleri, etkileri ve kardiyovasküler hastalıklar ile ilişkileri. Türk Aile Hek Derg. 2008; 12(3):121-9. doi:10.2399/tahd.08.121.
8. 18.Ahmad SO, Park J, Radel JD, Levant B. Reduced numbers of dopamine neurons in the substantia nigra pars compacta and ventral tegmental area of rats fed an n-3 polyunsaturated fatty acid-deficient diet: A stereological study. Neurosci Lett. 2008;438(3):303-7. doi: 10.1016/j.neulet.2008.04.073.

9. 19. McNamara RK, Liu Y, Jandacek R, Rider T, Tso P. The aging human orbitofrontal cortex: Decreasing polyunsaturated fatty acid composition and associated increases in lipogenic gene expression and stearoyl-CoA desaturase activity. Prostaglandins Leukot Essent Fatty Acids. 2008;78(4-5):293- 304. doi: 10.1016/j.plefa.2008.04.001
10. 20. Chen CT, Domenichiello AF, Trépanier M, Liu Z, Masoodi M, Bazinet RP. The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms. J Lipid Res. 2013;54(9):2410-22. doi: 10.1194/jlr.M038505. 21. Brenna JT, Salem N, Sinclair AJ, Cunnane SC. αLinolenic acid supplementation and conversion to n-3 longchain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids. 2009;80(2-3):85-91. doi: 10.1016/j.plefa.2009.01.004.
11. 22. National Institutes of Health Office of Dietary Supplements [Internet]. Bethesda (MD): U.S. Department of Health and Human Services. Omega-3 fatty acids; 2023 Feb 15 (cited 2023 Feb 20). Available from: https://ods.od.nih.gov/factsheets/Omega3FattyAcidsHealthProfessional/ 23. Guu T, Mischoulon D, Sarris J, Hibbeln J, McNamara RK, Hamazaki K, et al. International Society for Nutritional Psychiatry Research practice guidelines for omega-3 fatty acids in the treatment of major depressive disorder. Psychother Psychosom. 2019;88(5):263-73. doi: 10.1159/000502652.
12. 24. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion related to the Tolerable Upper Intake Level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). EFSA J. 2012;10(7):2815. doi: 10.2903/j.efsa.2012.2815
13. 25. U.S. Food and Drug Administration. Eicosapentaenoic acid and docosahexaenoic acid and reduction of blood pressure in the general population. [Internet] Silver Spring, MD: Food and Drug Administration; 2019 [Erişim tarihi: 10.11.2024]. Erişim adresi: https://www.fda.gov/food/foodlabeling-nutrition/qualified-health-claims-lettersenforcement-discretion
14. 26. Yee LD, Lester JL, Cole RM, Richardson JR, Hsu JC, Li Y, et al. ω-3 Fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition. Am J Clin Nutr. 2010;91(5):1185-94. doi: 10.3945/ajcn.2009.29036.
15. 27. Kim KY, Shin KY, Chang K. Potential inflammatory biomarkers for major depressive disorder related to suicidal behaviors: a systematic review. Int J Mol Sci. 2023;24(18):13907. doi: 10.3390/ijms241813907. 28. Gerrig JR, Zimbardo PG. Psychology life. 19th ed. New Jersey: Pearson Education; 2010. p. 454-5.
16. 29. Leonard BE. Inflammation, depression and dementia: are they connected?. Neurochem Res. 2007;32(10):1749-56. doi: 10.1007/s11064-007-9385-y. 30. Anacker C, Cattaneo A, Luoni A, Musaelyan K, Zunszain PA, Milanesi E, et al. Glucocorticoid-related molecular signaling pathways regulating hippocampal neurogenesis. Neuropsychopharmacol. 2013;38(5):872-83. doi: 10.1038/npp.2012.253.
17. 31. Su K, Huang S, Chiu C, Shen WW. Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol. 2003;13(4):267-71. doi: 10.1016/s0924-977x(03)00032-4.
18. 32. Lin P, Huang S, Su K. A Meta-analytic review of polyunsaturated fatty acid compositions in patients with depression. Biol Psychiatry. 2010;68(2):140-7. doi: 10.1016/j.biopsych.2010.03.018.
19. 33. Chiu C, Frangou S, Chang C, Chiu W, Liu H, Sun I, et al. Associations between n−3 PUFA concentrations and cognitive function after recovery from late-life depression. Am J Clin Nutr. 2012;95(2):420-7. doi: 10.3945/ajcn.111.015784.
20. 34. Mamalakis G, Tornaritis M, Kafatos A. Depression and adipose essential polyunsaturated fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2002;67(5):311-8. doi: 10.1054/plef.2002.0435. 35. McNamara RK, Strimpfel J, Jandacek R, Rider T, Tso P, Welge JA, et al. Detection and treatment of long-chain omega3 fatty acid deficiency in adolescents with SSRI-resistant major depressive disorder. PharmaNutrition. 2014;2(2):38- 46. doi: 10.1016/j.phanu.2014.02.002.
21. 36. Baek D, Park Y. Association between erythrocyte n-3 polyunsaturated fatty acids and biomarkers of inflammation and oxidative stress in patients with and without depression. Prostaglandins Leukot Essent Fatty Acids. 2013;89(5):291-6. doi: 10.1016/j.plefa.2013.09.008.
22. 37. Baghai TC, Varallo-Bedarida G, Born C, Häfner S, Schüle C, Eser D, et al. Major depressive disorder is associated with cardiovascular risk factors and low omega-3 index. J Clin Psychiatry. 2011;72(09):1242-7. doi: 10.4088/JCP.09m05895blu.
23. 38. Lotrich FE, Sears B, McNamara RK. Elevated ratio of arachidonic acid to long-chain omega-3 fatty acids predicts depression development following interferon-alpha treatment: relationship with interleukin-6. Brain Behav Immun. 2013;31:48-53. doi: 10.1016/j.bbi.2012.08.007.
24. 39. Duffy SL, Lagopoulos J, Cockayne N, Lewis SJ, Hickie IB, Hermens DF, et al. The effect of 12-wk ω-3 fatty acid supplementation on in vivo thalamus glutathione concentration in patients “at risk” for major depression. Nutrition. 2015;31(10):1247-54. doi: 10.1016/j.nut.2015.04.019.
25. 40. Scapagnini G, Davinelli S, Drago F, De Lorenzo A, Oriani G. Antioxidants as antidepressants: fact or fiction? CNS Drugs. 2012;26(6):477-90. doi: 10.2165/11633190- 000000000-00000.
26. 41. Yoshikawa E, Nishi D, Matsuoka Y. Fish consumption and resilience to depression in Japanese company workers: a cross-sectional study. Lipids Health Dis. 2015;14(1):51. doi: 10.1186/s12944-015-0048-8. 42. Sublette ME, Ellis SP, Geant AL, Mann JJ. Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry. 2011;72(12):1577-84. doi: 10.4088/JCP.10m06634. 43. Hegarty B, Parker G. Fish oil as a management component for mood disorders – an evolving signal. Curr Opin Psychiatry. 2013;26(1):33-40. doi: 10.1097/YCO.0b013e32835ab4a7.
27. 44. Maes M, Ruckoanich P, Chang YS, Mahanonda N, Berk M. Multiple aberrations in shared inflammatory and oxidative & nitrosative stress (IO&NS) pathways explain the coassociation of depression and cardiovascular disorder (CVD), and the increased risk for CVD and due mortality in depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(3):769-83. doi: 10.1016/j.pnpbp.2010.06.008.
28. 45. Zhou L, Xiong J, Chai Y, Huang L, Tang Z, Zhang X, et al. Possible antidepressant mechanisms of omega-3 polyunsaturated fatty acids acting on the central nervous system. Front Psychiatry. 2022;13:933704. doi: 10.3389/fpsyt.2022.933704.
29. 46. Grenyer BF, Crowe T, Meyer B, Owen AJ, GrigonisDeane EM, Caputi P, et al. Fish oil supplementation in the treatment of major depression: a randomised double-blind placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(7):1393-6. doi: 10.1016/j.pnpbp.2007.06.004.
30. 47. Freeman MP, Davis M, Sinha P, Wisner KL, Hibbeln JR, Gelenberg AJ. Omega-3 fatty acids and supportive psychotherapy for perinatal depression: a randomized placebo-controlled study. J Affect Disord. 2008;110(1- 2):142-8. doi: 10.1016/j.jad.2007.12.228. 48. Rees A, Austin M, Parker GB. Omega-3 fatty acids as a treatment for perinatal depression: randomized double-blind placebo-controlled trial. Aust N Z J Psychiatry.
31. 2008r;42(3):199-205. doi: 10.1080/00048670701827267. 49. Rogers PJ, Appleton KM, Kessler D, Peters TJ, Gunnell D, Hayward RC, et al. No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial. Br J Nutr. 2008;99(2):421-31. doi: 10.1017/S0007114507801097
32. 50. Su K, Huang S, Chiu T, Huang K, Huang C, Chang H, et al. Omega-3 fatty acids for major depressive disorder during pregnancy. J Clin Psychiatry. 2008;69(4):644-51. doi: 10.4088/jcp.v69n0418.
33. 51. Lucas M, Asselin G, Mérette C, Poulin M, Dodin S. Ethyleicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Am J Clin Nutr. 2009;89(2):641-51. doi: 10.3945/ajcn.2008.26749.
34. 52. Rondanelli M, Giacosa A, Opizzi A, Pelucchi C, La Vecchia C, Montorfano G, et al. Effect of omega-3 fatty acids supplementation on depressive symptoms and on healthrelated quality of life in the treatment of elderly women with depression: a double-blind, placebo-controlled, randomized clinical trial. J Am Coll Nutr. 2010;29(1):55-64. doi: 10.1080/07315724.2010.10719817.
35. 53. Tajalizadekhoob Y, Sharifi F, Fakhrzadeh H, Mirarefin M, Ghaderpanahi M, Badamchizade Z, et al. The effect of lowdose omega 3 fatty acids on the treatment of mild to moderate depression in the elderly: a double-blind, randomized, placebo-controlled study. Eur Arch Psychiatry Clin Neurosci. 2011;261(8):539-49. doi: 10.1007/s00406-011-0191-9.
36. 54. Lespérance F, Frasure-Smith N, St-André E, Turecki G, Lespérance P, Wisniewski SR. The efficacy of omega-3 supplementation for major depression. J Clin Psychiatry. 2011;72(8):1054-62. doi: 10.4088/JCP.10m05966blu.
37. 55. Gertsik L, Poland RE, Bresee C, Rapaport MH. Omega-3 fatty acid augmentation of citalopram treatment for patients with major depressive disorder. J Clin Psychopharmacol. 2012;32(1):61-4. doi: 10.1097/JCP.0b013e31823f3b5f. 56. Krawczyk K, Rybakowski J. Augmentation of antidepressants with unsaturated fatty acids omega-3 in drugresistant depression. Psychiatr Pol. 2012;46(4):585-98. 57. Rizzo AM, Corsetto PA, Montorfano G, Opizzi A, Faliva M, Giacosa A, et al. Comparison between the AA/EPA ratio in depressed and non depressed elderly females: omega-3 fatty acid supplementation correlates with improved symptoms but does not change immunological parameters. Nutr J. 2012;11:82. doi: 10.1186/1475-2891-11-82.