The importance of n-6/n-3 fatty acids ratio in the major depressive disorder

Medicina (Lithuania)

Volumn 52, Issue 3, 2016, Pages 139-147

  Husted, Kristian Søborg ^a   Bouzinova, Elena V ^a  

^a AARHUS UNIVERSITY   (Denmark)

Author keywords

Arachidonic acid; Depression; Eicosapentaenoic acid; Polyunsaturated fatty acids ratio

Indexed keywords

CYTOKINE; DOPAMINE; ICOSANOID; OMEGA 3 FATTY ACID; OMEGA 6 FATTY ACID; PHOSPHOLIPID; SEROTONIN;

BIOSYNTHESIS; CLINICAL TRIAL (TOPIC); DEPRESSIVE DISORDER, MAJOR; DIETARY SUPPLEMENT; GENE EXPRESSION REGULATION; HUMAN; HYPOTHALAMUS HYPOPHYSIS SYSTEM; MEMBRANE FLUIDITY; METABOLISM; WESTERN DIET;

CLINICAL TRIALS AS TOPIC; CYTOKINES; DEPRESSIVE DISORDER, MAJOR; DIET, WESTERN; DIETARY SUPPLEMENTS; DOPAMINE; EICOSANOIDS; FATTY ACIDS, OMEGA-3; FATTY ACIDS, OMEGA-6; GENE EXPRESSION REGULATION; HUMANS; HYPOTHALAMO-HYPOPHYSEAL SYSTEM; MEMBRANE FLUIDITY; PHOSPHOLIPIDS; SEROTONIN;

EID: 84977535204     PISSN: 1010660X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.medici.2016.05.003     Document Type: Review

References (105)

1. [1] Berton, O., Nestler, E.J., New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 7:2 (2006), 137–151.
2. [2] Su, K.P., Wang, S.M., Pae, C.U., Omega-3 polyunsaturated fatty acids for major depressive disorder. Expert Opin Investig Drugs 22:12 (2013), 1519–1534.
3. [3] The global burden of disease: 2004 update. 2008, World Health Organization, Geneva.
4. [4] Kessler, R.C., Bromet, E.J., The epidemiology of depression across cultures. Annu Rev Public Health 34 (2013), 119–138.
5. [5] Patten, S.B., Williams, J.V., Lavorato, D.H., Wang, J.L., McDonald, K., Bulloch, A.G., Descriptive epidemiology of major depressive disorder in Canada in 2012. Can J Psychiatry 60:1 (2015), 23–30.
6. [6] Avenevoli, S., Swendsen, J., He, J.P., Burstein, M., Merikangas, K.R., Major depression in the national comorbidity survey-adolescent supplement: prevalence, correlates, and treatment. J Am Acad Child Adolesc Psychiatry, 54(1), 2015 37–44.e2.
7. [7] Carta, M.G., Aguglia, E., Bocchetta, A., Balestrieri, M., Caraci, F., Casacchia, M., et al. The use of antidepressant drugs and the lifetime prevalence of major depressive disorders in Italy. Clin Pract Epidemiol Ment Health 6 (2010), 94–100.
8. [8] Klerman, G.L., The current age of youthful melancholia. Evidence for increase in depression among adolescents and young adults. Br J Psychiatry 152 (1988), 4–14.
9. [9] von Soest, T., Wichstrom, L., Secular trends in depressive symptoms among Norwegian adolescents from 1992 to 2010. J Abnorm Child Psychol 42:3 (2014), 403–415.
10. [10] Collishaw, S., Maughan, B., Natarajan, L., Pickles, A., Trends in adolescent emotional problems in England: a comparison of two national cohorts twenty years apart. J Child Psychol Psychiatry 51:8 (2010), 885–894.
11. [11] Sweeting, H., West, P., Young, R., Der, G., Can we explain increases in young people's psychological distress over time?. Soc Sci Med 71:10 (2010), 1819–1830.
12. [12] Simopoulos, A.P., Evolutionary aspects of the dietary omega-6:omega-3 fatty acid ratio: medical implications. World Rev Nutr Diet 100 (2009), 1–21.
13. [13] Logan, A.C., Neurobehavioral aspects of omega-3 fatty acids: possible mechanisms and therapeutic value in major depression. Altern Med Rev 8:4 (2003), 410–425.
14. [14] Simopoulos, A.P., Leaf, A., Salem, N. Jr., Workshop on the essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids. J Am Coll Nutr 18:5 (1999), 487–489.
15. [15] Weissman, M.M., Bland, R.C., Canino, G.J., Faravelli, C., Greenwald, S., Hwu, H.G., et al. Cross-national epidemiology of major depression and bipolar disorder. JAMA 276:4 (1996), 293–299.
16. [16] Hibbeln, J.R., Fish consumption and major depression. Lancet, 351(9110), 1998, 1213.
17. [17] The changing rate of major depression. Cross-national comparisons. Cross-National Collaborative Group. JAMA 268:21 (1992), 3098–3105.
18. [18] Hibbeln, J.R., Salem, N. Jr., Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Am J Clin Nutr 62:1 (1995), 1–9.
19. [19] 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 31:Suppl. (1996), S157–S161.
20. [20] Tiemeier, H., van Tuijl, H.R., Hofman, A., Kiliaan, A.J., Breteler, M.M., Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study. Am J Clin Nutr 78:1 (2003), 40–46.
21. [21] Maes, M., Smith, R., Christophe, A., Cosyns, P., Desnyder, R., Meltzer, H., Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20:4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. J Affect Disord 38:1 (1996), 35–46.
22. [22] Ross, B.M., Omega-3 fatty acid deficiency in major depressive disorder is caused by the interaction between diet and a genetically determined abnormality in phospholipid metabolism. Med Hypotheses 68:3 (2007), 515–524.
23. [23] 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 48:2–3 (1998), 149–155.
24. [24] 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 43:5 (1998), 315–319.
25. [25] 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, 2015.
26. [26] Conklin, S.M., Runyan, C.A., Leonard, S., Reddy, R.D., Muldoon, M.F., Yao, J.K., Age-related changes of n-3 and n-6 polyunsaturated fatty acids in the anterior cingulate cortex of individuals with major depressive disorder. Prostaglandins Leukot Essent Fatty Acids 82:2–3 (2010), 111–119.
27. [27] De Vriese, S.R., Christophe, A.B., Maes, M., In humans, the seasonal variation in poly-unsaturated fatty acids is related to the seasonal variation in violent suicide and serotonergic markers of violent suicide. Prostaglandins Leukot Essent Fatty Acids 71:1 (2004), 13–18.
28. [28] Lewis, M.D., Hibbeln, J.R., Johnson, J.E., Lin, Y.H., Hyun, D.Y., Loewke, J.D., Suicide deaths of active-duty US military and omega-3 fatty-acid status: a case–control comparison. J Clin Psychiatry 72:12 (2011), 1585–1590.
29. [29] Huan, M., Hamazaki, K., Sun, Y., Itomura, M., Liu, H., Kang, W., et al. Suicide attempt and n-3 fatty acid levels in red blood cells: a case control study in China. Biol Psychiatry 56:7 (2004), 490–496.
30. [30] Borup, V.D., Biokemi. 1st ed., 2012, FADL, København [chapter 41].
31. [31] Simopoulos, A.P., Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain. Mol Neurobiol 44:2 (2011), 203–215.
32. [32] Haag, M., Essential fatty acids and the brain. Can J Psychiatry 48:3 (2003), 195–203.
33. [33] Cho, H.P., Nakamura, M., Clarke, S.D., Cloning, expression, and fatty acid regulation of the human Delta-5 desaturase. J Biol Chem, 274, 1999.
34. [34] Cho, H.P., Nakamura, M., Clarke, S.D., Cloning, expression, and nutritional regulation of the mammalian Delta-6 desaturase. J Biol Chem 274:1 (1999), 471–477.
35. [35] Emken, E.A., Adlof, R.O., Gulley, R.M., Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males. Biochim Biophys Acta 1213:3 (1994), 277–288.
36. [36] Yehuda, S., Omega-6/omega-3 ratio and brain-related functions. World Rev Nutr Diet 92 (2003), 37–56.
37. [37] Lands, W.E., Biochemistry and physiology of n-3 fatty acids. FASEB J 6:8 (1992), 2530–2536.
38. [38] Calder, P.C., Omega-3 fatty acids and inflammatory processes. Nutrients 2:3 (2010), 355–374.
39. [39] Calder, P.C., Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta 1851:4 (2015), 469–484.
40. [40] Freese, R., Mutanan, M., Valsta, L.M., Salminen, I., Comparison of the effects of two diets rich in monounsaturated fatty acids differing in their linoleic/alpha-linolenic acid ratio on platelet aggregation. Thromb Haemost 71 (1994), 73–77.
41. [41] Culp, B.R., Titus, B.G., Lands, W.E., Inhibition of prostaglandin biosynthesis by eicosapentaenoic acid. Prostaglandins Med 3:5 (1979), 269–278.
42. [42] Cotman, C., Blank, M.L., Moehl, A., Snyder, F., Lipid composition of synaptic plasma membranes isolated from rat brain by zonal centrifugation. Biochemistry 8:11 (1969), 4606–4612.
43. [43] Yehuda, S., Rabinovitz, S., Carasso, R.L., Mostofsky, D.I., Fatty acids and brain peptides. Peptides 19:2 (1998), 407–419.
44. [44] Fernstrom, J.D., Effects of dietary polyunsaturated fatty acids on neuronal function. Lipids 34:2 (1999), 161–169.
45. [45] Pertinhez, T.A., Nakaie, C.R., Carvalho, R.S., Paiva, A.C., Tabak, M., Toma, F., et al. Conformational changes upon binding of a receptor loop to lipid structures: possible role in signal transduction. FEBS Lett 375:3 (1995), 239–242.
46. [46] Parker, G., Gibson, N.A., Brotchie, H., Heruc, G., Rees, A.M., Hadzi-Pavlovic, D., Omega-3 fatty acids and mood disorders. Am J Psychiatry 163:6 (2006), 969–978.
47. [47] Bourre, J.M., Francois, M., Youyou, A., Dumont, O., Piciotti, M., Pascal, G., et al. The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. J Nutr 119:12 (1989), 1880–1892.
48. [48] Bowen, R.A., Clandinin, M.T., Dietary low linolenic acid compared with docosahexaenoic acid alter synaptic plasma membrane phospholipid fatty acid composition and sodium-potassium ATPase kinetics in developing rats. J Neurochem 83:4 (2002), 764–774.
49. +)-ATPase activity during fatty acid deficiency. J Neurochem 22:1 (1974), 15–18.
50. [50] Heron, D.S., Shinitzky, M., Hershkowitz, M., Samuel, D., Lipid fluidity markedly modulates the binding of serotonin to mouse brain membranes. Proc Natl Acad Sci U S A 77:12 (1980), 7463–7467.
51. 3H]ketanserin binding to 5-HT2 prefrontal cortex receptors. Neurochem Int 27:6 (1995), 489–496.
52. [52] Fong, T.M., McNamee, M.G., Correlation between acetylcholine receptor function and structural properties of membranes. Biochemistry 25:4 (1986), 830–840.
53. [53] Kirilovsky, J., Steiner-Mordoch, S., Selinger, Z., Schramm, M., Lipid requirements for reconstitution of the delipidated beta-adrenergic receptor and the regulatory protein. FEBS Lett 183:1 (1985), 75–80.
54. [54] Baynes, J., Dominiczak, M.H., Medical biochemistry. 4th ed., 2014, Saunders, Edinburgh [chapter 40].
55. [55] Simopoulos, A.P., The role of fatty acids in gene expression: health implications. Ann Nutr Metab 40:6 (1996), 303–311.
56. [56] Clarke, S.D., Romsos, D.R., Leveille, G.A., Differential effects of dietary methyl esters of long-chain saturated and polyunsaturated fatty acids on rat liver and adipose tissue lipogenesis. J Nutr 107:7 (1977), 1170–1181.
57. [57] Clarke, S.D., Armstrong, M.K., Jump, D.B., Dietary polyunsaturated fats uniquely suppress rat liver fatty acid synthase and S14 mRNA content. J Nutr 120:2 (1990), 225–231.
58. [58] Hao, W., Wong, O.Y., Liu, X., Lee, P., Chen, Y., Wong, K.K., omega-3 fatty acids suppress inflammatory cytokine production by macrophages and hepatocytes. J Pediatr Surg 45:12 (2010), 2412–2418.
59. [59] Weldon, S.M., Mullen, A.C., Loscher, C.E., Hurley, L.A., Roche, H.M., Docosahexaenoic acid induces an anti-inflammatory profile in lipopolysaccharide-stimulated human THP-1 macrophages more effectively than eicosapentaenoic acid. J Nutr Biochem 18:4 (2007), 250–258.
60. [60] Lo, C.J., Chiu, K.C., Fu, M., Lo, R., Helton, S., Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NF kappa B activity. J Surg Res 82:2 (1999), 216–221.
61. [61] Novak, T.E., Babcock, T.A., Jho, D.H., Helton, W.S., Espat, N.J.N., NF-kappa B inhibition by omega-3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription. Am J Physiol Lung Cell Mol Physiol 284:1 (2003), L84–L89.
62. [62] De Caterina, R., Libby, P., Control of endothelial leukocyte adhesion molecules by fatty acids. Lipids 31:Suppl. (1996), S57–S63.
63. [63] Park, B.K., Park, S., Park, J.B., Park, M.C., Min, T.S., Jin, M., Omega-3 fatty acids suppress Th2-associated cytokine gene expressions and GATA transcription factors in mast cells. J Nutr Biochem 24:5 (2013), 868–876.
64. [64] Ciraulo, D.A., Shader, R.I., (eds.) Pharmacotherapy of depression, 2004, Humana Press, Totowa, NJ.
65. [65] Schildkraut, J.J., The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 122:5 (1965), 509–522.
66. [66] Brøsen, K., Simonsen, U., Kampmann, J.P., Thirstrup, S., Basal og klinisk farmakologi. 5ht ed., 2014, FADL, København [chapter 48].
67. [67] Maes, M., Smith, R.S., Fatty acids, cytokines, and major depression. Biol Psychiatry 43:5 (1998), 313–314.
68. [68] Smith, R.S., The macrophage theory of depression. Med Hypotheses 35:4 (1991), 298–306.
69. [69] Felger, J.C., Alagbe, O., Hu, F., Mook, D., Freeman, A.A., Sanchez, M.M., et al. Effects of interferon-alpha on rhesus monkeys: a nonhuman primate model of cytokine-induced depression. Biol Psychiatry 62:11 (2007), 1324–1333.
70. [70] Liu, Y., Ho, R.C., Mak, A., Interleukin (IL)-6, tumour necrosis factor alpha (TNF-alpha) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord 139:3 (2012), 230–239.
71. [71] Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E.K., et al. A meta-analysis of cytokines in major depression. Biol Psychiatry 67:5 (2010), 446–457.
72. [72] Dahl, J., Ormstad, H., Aass, H.C., Malt, U.F., Bendz, L.T., Sandvik, L., et al. The plasma levels of various cytokines are increased during ongoing depression and are reduced to normal levels after recovery. Psychoneuroendocrinology 45 (2014), 77–86.
73. [73] Suarez, E.C., Krishnan, R.R., Lewis, J.G., The relation of severity of depressive symptoms to monocyte-associated proinflammatory cytokines and chemokines in apparently healthy men. Psychosom Med 65:3 (2003), 362–368.
74. [74] Himmerich, H., Binder, E.B., Kunzel, H.E., Schuld, A., Lucae, S., Uhr, M., et al. Successful antidepressant therapy restores the disturbed interplay between TNF-alpha system and HPA axis. Biol Psychiatry 60:8 (2006), 882–888.
75. [75] O'Brien, S.M., Scott, L.V., Dinan, T.G., Cytokines: abnormalities in major depression and implications for pharmacological treatment. Hum Psychopharmacol 19:6 (2004), 397–403.
76. [76] Sachar, E.J., Hellman, L., Roffwarg, H.P., Halpern, F.S., Fukushima, D.K., Gallagher, T.F., Disrupted 24-hour patterns of cortisol secretion in psychotic depression. Arch Gen Psychiatry 28:1 (1973), 19–24.
77. [77] Barden, N., Implication of the hypothalamic-pituitary-adrenal axis in the physiopathology of depression. J Psychiatry Neurosci 29:3 (2004), 185–193.
78. [78] Gillespie, C.F., Nemeroff, C.B., Hypercortisolemia and depression. Psychosom Med 67:Suppl. 1 (2005), S26–S28.
79. [79] Christiansen, S., Bouzinova, E.V., Palme, R., Wiborg, O., Circadian activity of the hypothalamic-pituitary-adrenal axis is differentially affected in the rat chronic mild stress model of depression. Stress 15:6 (2012), 647–657.
80. [80] Maes, M., Leonard, B.E., Myint, A.M., Kubera, M., Verkerk, R., The new ‘5-HT’ hypothesis of depression: cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression. Prog Neuropsychopharmacol Biol Psychiatry 35:3 (2011), 702–721.
81. [81] Myint, A.M., Bondy, B., Baghai, T.C., Eser, D., Nothdurfter, C., Schule, C., et al. Tryptophan metabolism and immunogenetics in major depression: a role for interferon-gamma gene. Brain Behav Immun 31 (2013), 128–133.
82. [82] Mossner, R., Heils, A., Stober, G., Okladnova, O., Daniel, S., Lesch, K.P., Enhancement of serotonin transporter function by tumor necrosis factor alpha but not by interleukin-6. Neurochem Int 33:3 (1998), 251–254.
83. [83] Morikawa, O., Sakai, N., Obara, H., Saito, N., Effects of interferon-alpha, interferon-gamma and cAMP on the transcriptional regulation of the serotonin transporter. Eur J Pharmacol 349:2–3 (1998), 317–324.
84. [84] Tsao, C.W., Lin, Y.S., Chen, C.C., Bai, C.H., Wu, S.R., Cytokines and serotonin transporter in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry 30:5 (2006), 899–905.
85. [85] Delion, S., Chalon, S., Guilloteau, D., Besnard, J.C., Durand, G., alpha-Linolenic acid dietary deficiency alters age-related changes of dopaminergic and serotoninergic neurotransmission in the rat frontal cortex. J Neurochem 66:4 (1996), 1582–1591.
86. [86] Khorsan, R., Crawford, C., Ives, J.A., Walter, A.R., Jonas, W.B., The effect of omega-3 fatty acids on biomarkers of inflammation: a rapid evidence assessment of the literature. Mil Med 179:11 Suppl. (2014), 2–60.
87. [87] Chalon, S., Delion-Vancassel, S., Belzung, C., Guilloteau, D., Leguisquet, A.M., Besnard, J.C., et al. Dietary fish oil affects monoaminergic neurotransmission and behavior in rats. J Nutr 128:12 (1998), 2512–2519.
88. [88] Delion, S., Chalon, S., Herault, J., Guilloteau, D., Besnard, J.C., Durand, G., Chronic dietary alpha-linolenic acid deficiency alters dopaminergic and serotoninergic neurotransmission in rats. J Nutr 124:12 (1994), 2466–2476.
89. [89] Chalon, S., Vancassel, S., Zimmer, L., Guilloteau, D., Durand, G., Polyunsaturated fatty acids and cerebral function: focus on monoaminergic neurotransmission. Lipids 36:9 (2001), 937–944.
90. [90] Zimmer, L., Delpal, S., Guilloteau, D., Aioun, J., Durand, G., Chalon, S., Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex. Neurosci Lett 284:1–2 (2000), 25–28.
91. [91] Zimmer, L., Vancassel, S., Cantagrel, S., Breton, P., Delamanche, S., Guilloteau, D., et al. The dopamine mesocorticolimbic pathway is affected by deficiency in n-3 polyunsaturated fatty acids. Am J Clin Nutr 75:4 (2002), 662–667.
92. [92] Zimmer, L., Delion-Vancassel, S., Durand, G., Guilloteau, D., Bodard, S., Besnard, J.C., et al. Modification of dopamine neurotransmission in the nucleus accumbens of rats deficient in n-3 polyunsaturated fatty acids. J Lipid Res 41:1 (2000), 32–40.
93. [93] Stoll, A.L., Severus, W.E., Freeman, M.P., Rueter, S., Zboyan, H.A., Diamond, E., et al. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry 56:5 (1999), 407–412.
94. [94] Nemets, B., Stahl, Z., Belmaker, R.H., Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Am J Psychiatry 159:3 (2002), 477–479.
95. [95] Frangou, S., Lewis, M., McCrone, P., Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Br J Psychiatry 188 (2006), 46–50.
96. [96] Jazayeri, S., Tehrani-Doost, M., Keshavarz, S.A., Hosseini, M., Djazayery, A., Amini, H., et al. Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Aust N Z J Psychiatry 42:3 (2008), 192–198.
97. [97] Puri, B.K., Counsell, S.J., Hamilton, G., Richardson, A.J., Horrobin, D.F., Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover. Int J Clin Pract 55:8 (2001), 560–563.
98. [98] Peet, M., Horrobin, D.F., A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry 59:10 (2002), 913–919.
99. [99] Mischoulon, D., Best-Popescu, C., Laposata, M., Merens, W., Murakami, J.L., Wu, S.L., et al. A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major depressive disorder. Eur Neuropsychopharmacol 18:9 (2008), 639–645.
100. [100] Mischoulon, D., Papakostas, G.I., Dording, C.M., Farabaugh, A.H., Sonawalla, S.B., Agoston, A.M., et al. A double-blind, randomized controlled trial of ethyl-eicosapentaenoate for major depressive disorder. J Clin Psychiatry 70:12 (2009), 1636–1644.
101. [101] Marangell, L.B., Martinez, J.M., Zboyan, H.A., Kertz, B., Kim, H.F., Puryear, L.J., A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Am J Psychiatry 160:5 (2003), 996–998.
102. [102] Su, K.P., Huang, S.Y., Chiu, C.C., Shen, W.W., Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol 13:4 (2003), 267–271.
103. [103] Nemets, H., Nemets, B., Apter, A., Bracha, Z., Belmaker, R.H., Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry 163:6 (2006), 1098–1100.
104. [104] Silvers, K.M., Woolley, C.C., Hamilton, F.C., Watts, P.M., Watson, R.A., Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression. Prostaglandins Leukot Essent Fatty Acids 72:3 (2005), 211–218.
105. [105] Grenyer, B.F., Crowe, T., Meyer, B., Owen, A.J., Grigonis-Deane, E.M., Caputi, P., et al. Fish oil supplementation in the treatment of major depression: a randomised double-blind placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry 31:7 (2007), 1393–1396.