Omega-3 polyunsaturated fatty acids and depression: A review of the evidence

Current Pharmaceutical Design

Volumn 15, Issue 36, 2009, Pages 4165-4172

  Liperoti, R ^a   Landi, F ^a   Fusco, O ^a   Bernabei, R ^a   Onder, G ^a  

^a CATHOLIC UNIVERSITY   (Italy)

Author keywords

Depression; DHA; EPA; Omega 3 fatty acids; Polyunsaturated fatty acids

Indexed keywords

ANTIDEPRESSANT AGENT; DOCOSAHEXAENOIC ACID; FISH OIL; FLUOXETINE; GLUCOSE; ICOSAPENTAENOIC ACID; ICOSAPENTAENOIC ACID ETHYL ESTER; OMEGA 3 FATTY ACID; PAROXETINE; PLACEBO;

ADD ON THERAPY; ADJUVANT THERAPY; APOPTOSIS; BIPOLAR DISORDER; CELL GROWTH; CELL MEMBRANE FLUIDITY; CLINICAL TRIAL; DEPRESSION; DIET SUPPLEMENTATION; DIETARY INTAKE; DISEASE ASSOCIATION; DOPAMINERGIC TRANSMISSION; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; EVIDENCE BASED MEDICINE; FATTY ACID BLOOD LEVEL; FISH; GENE EXPRESSION; GLUCOSE METABOLISM; HAMILTON SCALE; HUMAN; LIPID BRAIN LEVEL; LOW DRUG DOSE; MAJOR DEPRESSION; NONHUMAN; PRIORITY JOURNAL; PUERPERAL DEPRESSION; RAPID CYCLING BIPOLAR DISORDER; REVIEW; SEROTONINERGIC TRANSMISSION; SIGNAL TRANSDUCTION;

BIPOLAR DISORDER; DEPRESSIVE DISORDER; FATTY ACIDS, OMEGA-3; HUMANS;

EID: 71849103346     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161209789909683     Document Type: Review

References (102)

1. Emken EA, Adlof RO, Gulley RM. Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males. Biochim Biophys Acta 1994; 1213: 277-288
2. Pawlosky RJ, Salem N Jr. Ethanol exposure causes a decrease in docosahexaenoic acid and an increase in docosapentaenoic acid in feline brains and retinas. Am J Clin Nutr 1995; 61: 1284-1289
3. Pawlosky RJ, Hibbeln JR, Salem N Jr. Compartmental analyses of plasma n-3 essential fatty acids among male and female smokers and nonsmokers. J Lipid Res 2007; 48: 935-943
4. Tassoni D, Kaur G, Weisinger RS, Sinclair AJ. The role of eicosanoids in the brain. Asia Pac J Clin Nutr 2008; 17 (Suppl 1): 220-228 Review
5. Benatti P, Peluso G, Nicolai R, Calvani M. Polyunsaturated fatty acids: biochemical, nutritional and epigenetic properties. J Am Coll Nutr 2004; 23: 281-302 (Pubitemid 39096388)
6. Litman BJ, Niu SL, Polozova A, Mitchell DC. The role of docosahexaenoic acid containing phospholipids in modulating G protein-coupled signaling pathways: visual transduction. J Mol Neurosci 2001; 16: 237-242 (Pubitemid 32664785)
7. 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 2002; 75: 662-667 (Pubitemid 34250678)
8. Chalon S, Vancassel S, Zimmer L, Guilloteau D, Durand G. Polyunsaturated fatty acids and cerebral function: focus on monoaminergic neurotransmission. Lipids 2001; 36: 937-944 (Pubitemid 33065195)
9. Zimmer L, Delion-Vancassel S, Durand G, Guilloteau D, Bodard S, Besnard JC, et al Modification of dopamine neurotransmission in the nucleus accumbens of rats deficient in n-3 polyunsaturated fatty acids. J Lipid Res 2000; 41: 32-40 (Pubitemid 30051839)
10. Vaidyanathan VV, Rao KV, Sastry PS. Regulation of diacylglycerol kinase in rat brain membranes by docosahexaenoic acid. Neurosci Lett 1994; 179: 171-174 (Pubitemid 24298585)
11. McNamara RK, Ostrander M, Abplanalp W, Richtand NM, Benoit SC, Clegg DJ. Modulation of phosphoinositide-protein kinase C signal transduction by omega-3 fatty acids: implications for the pathophysiology and treatment of recurrent neuropsychiatric illness. Prostaglandins Leukot Essent Fatty Acids 2006; 75: 237-257 (Pubitemid 44442916)
12. Ximenes da Silva A, Lavialle F, Gendrot G, Guesnet P, Alessandri JM, Lavialle M. Glucose transport and utilization are altered in the brain of rats deficient in n-3 polyunsaturated fatty acids. J Neurochem 2002; 81: 1328-1337 (Pubitemid 34809266)
13. Pifferi F, Roux F, Langelier B, Alessandri JM, Vancassel S, Jouin M, et al. (n-3) polyunsaturated fatty acid deficiency reduces the expression of both isoforms of the brain glucose transporter GLUT1 in rats. J Nutr 2005; 135: 2241-2246 (Pubitemid 41298394)
14. Bazan NG. Neuroprotectin D1 (NPD1): a DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress. Brain Pathol 2005; 15: 159-166
15. Calder PC. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 2006; 83(6 Suppl): 1505S-1519S
16. Hong S, Gronert K, Devchand PR, Moussignac RL, Serhan CN. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J Biol Chem 2003; 278: 14677-14687 (Pubitemid 36799790)
17. Kuperstein F, Eilam R, Yavin E. Altered expression of key dopaminergic regulatory proteins in the postnatal brain following perinatal n-3 fatty acid dietary deficiency. J Neurochem 2008; 106: 662-671
18. Rao JS, Ertley RN, DeMar JC Jr, Rapoport SI, Bazinet RP, Lee HJ. Dietary n-3 PUFA deprivation alters expression of enzymes of the arachidonic and docosahexaenoic acid cascades in rat frontal cortex. Mol Psychiatry 2007; 12: 151-157
19. Calderon F, Kim HY. Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem 2004; 90: 979-988 (Pubitemid 39099980)
20. Darios F, Davletov B. Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3. Nature 2006; 440: 813-817
21. Mukherjee PK, Chawla A, Loayza MS, Bazan NG. Docosanoids are multifunctional regulators of neural cell integrity and fate: significance in aging and disease. Prostaglandins Leukot Essent Fatty Acids 2007; 77: 233-238 (Pubitemid 350198868)
22. Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 2002; 21: 495-505 (Pubitemid 36026261)
23. Young G, Conquer J. Omega-3 fatty acids and neuropsychiatric disorders. Reprod Nutr Dev 2005; 45: 1-28 (Pubitemid 40528530)
24. Ellis FR, Sanders TA. Long chain polyunsaturated fatty acids in endogenous depression. J Neurol Neurosurg Psychiatry 1977; 40: 168-169
25. Fehily AM, Bowey O, Ellis FR, Meade BW. Plasma and erythrocyte membrane long chain polyunsaturated fatty acids in endogenous depression. Neurochem Int 1981; 5: 37-42 (Pubitemid 11079899)
26. Pekkanen J, Nissinen A, Punsar S, Karvonen MJ. Serum cholesteroland the risk of accidental or violent death in a 25 year follow-up: the Finnish cohorts of the Seven Countries Study. Arch Intern Med 1989; 149: 1589-1591 (Pubitemid 19177632)
27. Connor WE, Connor SL. In: Rifkind BM, Levy RI, Eds. Hyperlipidemia: diagnosis and therapy. New York: Grune and Stratton 1977; pp. 281-326
28. Kaplan JR, Manuck SB, Shively C. The effects of fat and cholesterol on social behavior in monkeys. Psychosom Med 1991; 53: 634-642
29. Adams PB, Lawson S, Sanigorski A, Sinclair AJ. Arachidonic acid to eicosapaentanoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids 1996; 31: S157-61 (Pubitemid 126673804)
30. Maes M, Christophe A, Delanghe J, Altamura C, Neels H, Meltzer HY. Lowered omega3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res 1999; 85: 275-291 (Pubitemid 29202389)
31. Puri BK, Counsell SJ, Hamilton G, Richardson AJ, Horrobin DF. Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover. Int J Clin Pract 2001; 55: 560-563 (Pubitemid 33040558)
32. Chih-Chiang C, Shih-Yi H, Winston WS, Kuan-Pin S. Omega-3 fatty acids for depression in pregnancy. Am J Psychiatry 2003; 160: 385
33. Hibbeln JR. Fish consumption and major depression. Lancet 1998; 351: 1213
34. Hibbeln JR. Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a crossnational, ecological analysis. J Affect Disord 2002; 69: 15-29
35. Mamalakis G, Tornaritis M, Kafatos A. Depression and adipose essential polyunsaturated fatty acids. Prostaglandins Leukot Essent Fatty Acids 2002; 67: 311-318 (Pubitemid 35397372)
36. Mamalakis G, Kiriakakis M, Tsibinos G, Kafatos A. Depression and adipose polyunsaturated fatty acids in the survivors of the Seven Countries Study population of Crete. Prostaglandins Leukot Essent Fatty Acids 2004; 70: 495-501 (Pubitemid 38621892)
37. Mamalakis G, Kalogeropoulos N, Andrikopoulos N, Hatzis C, Kromhout D, Moschandreas J, et al. Depression and long chain n-3 fatty acids in adipose tissue in adults from Crete. Eur J Clin Nutr 2006; 60: 882-888 (Pubitemid 43997701)
38. Peet M, Mutphy 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 (Pubitemid 28137622)
39. 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 (Pubitemid 28244216)
40. 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: 891-896 (Pubitemid 38526301)
41. Parker GB, Heruc GA, Hilton TM, Olley A, Brotchie H, Hadzi.Pavlovic D, et al. Low levels of dcosahexaenoic acid identified in acute coronary syndrome patients with depression. Psychiatry Res 2006; 141: 279-286
42. Tiemeier H, van Tuijl HR, Hofman A, Kiliaan AJ, Breteler MM. Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study. Am J Clin Nutr 2003; 78: 40-46 (Pubitemid 39655246)
43. Crowe FL, Skeaff CM, Green TJ, Gray AR. Serum phospholipid n 3 long-chain polyunsaturated fatty acids and physical and mental health in a population-based survey of New Zealand adolescents and adults. Am J Clin Nutr 2007; 86: 1278-1285
44. Tanskanen A, Hibbeln JR, Tuomilehto J, Uutela A, Haukkala A, Viinamäki H, et al. Fish consumption and depressive symptoms in the general population in Finland. Psychiatr Serv 2001; 52: 529-531 (Pubitemid 32275317)
45. Silvers KM, Scott KM. Fish consumption and self-reported physical and mental health status. Public Health Nutr 2002; 5: 427-431
46. Suzuki S, Akechi T, Kobayashi M, Taniguchi K, Goto K, Sasaki S, et al. Daily omega-3 fatty acid intake and depression in Japanese patients with newly diagnosed lung cancer. Br J Cancer 2004; 90: 787-793 (Pubitemid 38406587)
47. Sublette ME, Hibbeln JR, Galfalvy H, Oquendo MA, Mann JJ. Omega-3 polyunsaturated essential fatty acid status as a predictor of future suicide risk. Am J Psychiatry 2006; 163: 1100-1102 (Pubitemid 44464499)
48. Hakkarainen R, Partonen T, Haukka J, Virtamo J, Albanes D, Lönnqvist J. Is low dietary intake of omega-3 fatty acids associated with depression? Am J Psychiatry 2004; 161: 567-569
49. Otto SJ, de Groot RH, Hornstra G. Increased risk of postpartum depressive symptoms is associated with slower normalization after pregnancy of the functional docosahexaenoic acid status. Prostaglandins Leukot Essent Fatty Acids 2003; 69: 237-243 (Pubitemid 37463804)
50. De Vriese SR, Christophe AB, Maes M. Lowered serum n-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression. Life Sci 2003; 73: 3181-3187 (Pubitemid 37242978)
51. Browne JC, Scott KM, Silvers KM. Fish consumption in pregnancy and omega-3 status after birth are not associated with postnatal depression. J Affect Disord 2006; 90: 131-139
52. Miyake Y, Sasaki S, Yokoyama T, Tanaka K, Ohya Y, Fukushima W, et al.; Osaka Maternal and Child Health Study Group. Risk of postpartum depression in relation to dietary fish and fat intake in Japan: the Osaka Maternal and Child Health Study. Psychol Med 2006; 36: 1727-1735
53. Astorg P, Couthouis A, Bertrais S, Arnault N, Meneton P, Guesnet P, et al. Association of fish and long-chain n-3 polyunsaturated fatty acid intakes with the occurrence of depressive episodes in middle-aged French men and women. Prostaglandins Leukot Essent Fatty Acids 2008; 78: 171-182
54. Peet M, Horrobin DF. A dose-ranging study of the effects of ethyleicosapentaenoate in patients with ongoing despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry 2002; 59: 913-919
55. Nemets B, Stahl Z, Belmaker RH. Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Am J Psychiatry 2002; 159: 477-479 (Pubitemid 34184747)
56. Su KP, Huang SY, Chiu CC, Shen WW. Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol 2003; 13: 267-271
57. Marangell LB, Martinez JM, Zboyan HA, Kertz B, Kim HF, Puryear LJ. A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Am J Psychiatry 2003; 160: 996-998 (Pubitemid 41079588)
58. Silvers KM, Woolley CC, Hamilton FC, Watts PM, Watson RA. Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression. Prostaglandins Leukot Essent Fatty Acids 2005; 72: 211-218 (Pubitemid 40139086)
59. Grenyer BF, Crowe T, Meyer B, Owen AJ, Grigonis-Deane 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: 1393-1396 (Pubitemid 47304478)
60. 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: 421-431
61. Jazayeri S, Tehrani-Doost M, Keshavarz SA, 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 2008; 42: 192-198 (Pubitemid 351234188)
62. Stoll Al, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E, et al. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry 1999; 56: 407-412 (Pubitemid 29215428)
63. Osher Y, Bersudsky Y, Belmaker RH. Omega-3 eicosapentaenoic acid in bipolar depression: report of a small open-label study. J Clin Psychiatry 2005; 66: 726-729 (Pubitemid 40942418)
64. Frangou S, Lewis M, McCrone P. Efficacy of ethyleicosapentaenoic acid in bipolar depression: randomised doubleblind placebo-controlled study. Br J Psychiatry 2006; 188: 46-50 (Pubitemid 43021926)
65. Keck PE Jr, Mintz J, McElroy SL, Freeman MP, Suppes T, Frye MA, et al. Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biol Psychiatry 2006; 60: 1020-1022 (Pubitemid 44739928)
66. Llorente AM, Jensen CL, Voigt RG, Fraley JK, Berretta MC, Heird WC. Effect of maternal docosahexaenoic acid supplementation on postpartum depression and information processing. Am J Obstet Gynecol 2003; 188: 1348-1353
67. Marangell LB, Martinez JM, Zboyan HA, Chong H, Puryear LJ. Omega-3 fatty acids for the prevention of postpartum depression: negative data from a preliminary, open-label pilot study. Depress Anxiety 2004; 19: 20-23 (Pubitemid 38294605)
68. Su KP, Huang SY, Chiu TH, Huang KC, Huang CL, Chang HC, et al. Omega-3 fatty acids for major depressive disorder during pregnancy: results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2008; 69: 644-651 (Pubitemid 351792341)
69. Rees AM, Austin MP, Parker GB. Omega-3 fatty acids as a treatment for perinatal depression: randomized double-blind placebo-controlled trial. Aust N Z J Psychiatry 2008; 42: 199-205 (Pubitemid 351234189)
70. Freeman MP, Davis M, Sinha P, Wisner KL, Hibbeln JR, Glenberg AJ. Omega-3 fatty acids and supportive psychotherapy for perinatal depression: a randomized placebo-controlled study. J Affect Disord 2008; 110: 142-148
71. Appleton KM, Hayward RC, Gunnell D, Peters TJ, Rogers PJ, Kessler D, et al. Effects of n-3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials. Am J Clin Nutr 2006; 84: 1308-1316 (Pubitemid 44912811)
72. Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry 2007; 68: 1056-1061
73. Damico KE, Stoll AL, Marangell LB, Cohen BM. How blind is double-blind? A study of fish oil versus placebo. Prostaglandins Leukot Essent Fatty Acids 2002; 66: 393-395
74. Dworkin RH, Katz J, Gitlin MJ. Placebo response in clinical trials of depression and its implications for research on chronic neuropathic pain. Neurology 2005; 65: S7-19 (Pubitemid 43755488)
75. van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Hoefnagels WH, Beekman AT, et al. Effect of fish-oil supplementation on mental well-being in older subjects: a randomized double-blind, placebo-controlled trial. Am J Clin Nutr 2008; 88: 706-713
76. Zimmer L, Delion-Vancassel S, Durand G, Guilloteau D, Bodard S, Besnard JC, et al. Modification of dopamine neurotransmission in the nucleus accumbens of rats deficient in n-3 polyunsaturated fatty acids. J Lipid Res 2000; 41: 32-40 (Pubitemid 30051839)
77. Chalon S, Delion-Vancassel S, Belzung C, Guilloteau D, Leguisquet AM, Besnard JC, et al. Dietary fish oil affects monoaminergic neurotransmission and behavior in rats. J Nutr 1998; 128: 2512-2519 (Pubitemid 29013003)
78. Périco CA, Skaf CR, Yamada A, Duran F, Buchpiguel CA, Castro CC, et al. Relationship between regional cerebral blood flow and separate symptom clusters of major depression: a single photon emission computed tomography study using statistical parametric mapping. Neurosci Lett 2005; 384: 265-270 (Pubitemid 40836012)
79. Kimbrell TA, George MS, Parekh PI, Ketter TA, Podell DM, Danielson AL, et al. Regional brain activity during transient self-induced anxiety and anger in healthy adults. Biol Psychiatry 1999 Aug 15; 46: 454-465
80. Lee KM, Kim YK. The role of IL-12 and TGF-beta1 in the pathophysiology of major depressive disorder. Int Immunopharmacol 2006; 6: 1298-1304 (Pubitemid 43890961)
81. Wichers M, Maes M. The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans. Int J Neuropsychopharmacol 2002; 5: 375-388
82. Xia Z, DePierre JW, Nässberger L.Tricyclic antidepressants inhibit IL-6, IL-1 beta and TNF-alpha release in human blood monocytes and IL-2 and interferon-gamma in T cells. Immunopharmacology 1996; 34: 27-37
83. Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, et al. Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 2003; 54: 70-75 (Pubitemid 36776725)
84. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron 2002; 34: 13-25
85. Russo-Neustadt AA, Chen MJ. Brain-derived neurotrophic factor and antidepressant activity. Curr Pharm Des 2005; 11: 1495-1510 (Pubitemid 40691448)
86. Fossati P, Radtchenko A, Boyer P. Neuroplasticity: from MRI to depressive symptoms. Eur Neuropsychopharmacol 2004; 14: S503-10
87. Molteni R, Barnard RJ, Ying Z, Roberts CK, Gómez-Pinilla F. A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience 2002; 112: 803-814 (Pubitemid 34667045)
88. Molteni R, Wu A, Vaynman S, Ying Z, Barnard RJ, Gómez-Pinilla F. Exercise reverses the harmful effects of consumption of a high-fat diet on synaptic and behavioral plasticity associated to the action of brain-derived neurotrophic factor. Neuroscience 2004; 123: 429-440 (Pubitemid 38032919)
89. Wu A, Molteni R, Ying Z, Gomez-Pinilla F. A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic factor. Neuroscience 2003; 119: 365-375 (Pubitemid 36588816)
90. Rao JS, Ertley RN, Lee HJ, DeMar JC Jr, Arnold JT, Rapoport SI, et al. n-3 polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism. Mol Psychiatry 2007; 12: 36-46
91. Ross BM. 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 2007; 68: 515-524
92. Papadimitriou GN, Dikeos DG, Souery D, Del-Favero J, Massat I, Avramopoulos D, et al. Genetic association between the phospholipase A2 gene and unipolar affective disorder: a multicentre case-control study. Psychiatr Genet 2003; 13: 211-220 (Pubitemid 38033106)
93. Pae CU, Yu HS, Kim JJ, Lee CU, Lee SJ, Lee KU, et al. BanI polymorphism of the cytosolic phospholipase A2 gene and mood disorders in the Korean population. Neuropsychobiology 2004; 49: 185-188 (Pubitemid 38594569)
94. Covault J, Pettinati H, Moak D, Mueller T, Kranzler HR. Association of a long-chain fatty acid-CoA ligase 4 gene polymorphism with depression and with enhanced niacin-induced dermal erythema. Am J Med Genet B Neuropsychiatr Genet 2004; 127B: 42-47 (Pubitemid 38542311)
95. Issa AM, Mojica WA, Morton SC, Traina S, Newberry SJ, Hilton LG, et al. The efficacy of omega-3 fatty acids on cognitive function in aging and dementia: a systematic review. Dement Geriatr Cogn Disord 2006; 21: 88-96 (Pubitemid 43107134)
96. Cole GM, Frautschy SA. Docosahexaenoic acid protects from amyloid and dendritic pathology in an Alzheimer's disease mouse model. Nutr Health 2006; 18: 249-259 (Pubitemid 44844123)
97. Palmer K, Berger AK, Monastero R, Winblad B, Backman L, Fratiglioni L. Predictors of progression from mild cognitive impairment to Alzheimer disease. Neurology 2007; 68: 1596-1602 (Pubitemid 46717984)
98. Green RC, Cupples LA, Kurz A, Auerbach S, Go R, Sadovnick D, et al. Depression as a risk factor for Alzheimer disease: the MIRAGE Study. Arch Neurol 2003; 60: 753-759 (Pubitemid 36569895)
99. Fischer C, Schweizer TA, Atkins JH, Bozanovic R, Norris M, Herrmann N, et al. Neurocognitive profiles in older adults with and without major depression. Int J Geriatr Psychiatry 2008; 23: 851-856
100. Alamo C, Lopez-Munoz F. New antidepressant drugs: beyond monoaminergic mechanisms. Curr Pharm Des 2009; 15(14): 1559-1562
101. Chen Z, Yang J, Tobak A. Designing new treatments for depression and anxiety. IDrugs 2008; 11(3): 189-197 (Pubitemid 351323373)
102. Nishida A, Miyaoka T, Inagaki T, Horiguchi J. New approaches to antidepressant drug design: cytokine-regulated pathways. Curr Pharm Des 2009; 15(14): 1683-1687