The role of fatty acids in the development and treatment of mood disorders

Current Opinion in Psychiatry

Volumn 21, Issue 1, 2008, Pages 19-24

  Owen, Catherine ^a   Rees, Anne Marie ^a   Parker, Gordon ^a  

^a BLACK DOG INSTITUTE   (Australia)

Author keywords

Bipolar disorder; Depression; Mood disorders; Omega 3; Polyunsaturated fatty acids

Indexed keywords

CARBAMAZEPINE; DOCOSAHEXAENOIC ACID; FATTY ACID; ICOSAPENTAENOIC ACID; ICOSAPENTAENOIC ACID ETHYL ESTER; LINOLENIC ACID; LITHIUM; OMEGA 3 FATTY ACID; PLACEBO; VALPROIC ACID;

ANTIINFLAMMATORY ACTIVITY; BIPOLAR DISORDER; BRAIN FUNCTION; BRAIN SIZE; BRAIN TISSUE; CLINICAL TRIAL; DEPRESSION; DISEASE COURSE; DRUG MECHANISM; EVIDENCE BASED PRACTICE; HEART DISEASE; HUMAN; MEDICAL RESEARCH; MOOD DISORDER; NONHUMAN; PUERPERAL DEPRESSION; REVIEW; SUICIDE;

ADULT; AFFECT; ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTIDEPRESSIVE AGENTS; BIPOLAR DISORDER; BRAIN; CHILD; CLINICAL TRIALS AS TOPIC; DEPRESSIVE DISORDER; DISEASE MODELS, ANIMAL; DRUG RESISTANCE; DRUG THERAPY, COMBINATION; FATTY ACIDS, OMEGA-3; HUMANS; RECURRENCE; RISK FACTORS;

EID: 40349092930     PISSN: 09517367     EISSN: None     Source Type: Journal    
DOI: 10.1097/YCO.0b013e3282f29841     Document Type: Review

References (46)

1. Hibbeln JR, Salem N Jr. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Am J Clin Nutr 1995; 62:1-9.
2. Hibbeln JR. Fish consumption and major depression. Lancet 1998; 351:1213.
3. Noaghiul S, Hibbeln JR. Cross-national comparisons of seafood consumption and rates of bipolar disorders. Am J Psychiatry 2003; 160:2222-2227.
4. Hibbeln JR. Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord 2002; 69:15-29.
5. 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. This interesting review highlights the fact that evidence for a relationship between omega-3 depletion and depression is much stronger when measuring omega-3 tissue levels than when using dietary intake of omega-3 as a proxy measure. The author proposes that this is not just due to the lower reliability of self-report dietary measures, but in fact indicates that omega-3 depletion is due to a combination of low dietary intake and a genetically determined deficit in omega-3 metabolism.
6. Stoll AL, Severus WE, Freeman MP, et al. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry 1999; 56:407-412.
7. Peet M, Horrobin DF. A dose-ranging study of the effects of ethyleicosapentanoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry 2002; 59:913-919.
8. 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.
9. Zanarini MC, Frankenburg FR. Omega-3 fatty acid treatment of women with borderline personality disorder: a double-blind, placebo-controlled pilot study. Am J Psychiatry 2003; 160:167-169.
10. 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.
11. Marangell LB, Martinez JM, Zboyan HA, et al. 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.
12. Silvers KM, Wooley CC, Hamilton FC, et al. Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression. Prostaglandins Leukot Essent Fatty Acids 2005; 72:211-218.
13. Parker G, Gibson NA, Brotchie H, et al. Omega-3 fatty acids and mood disorder. Am J Psychiatry 2006; 163:969-978. This is a comprehensive review of the epidemiological, case-control and clinical trial research conducted on the association between omega-3 deficiency and mood disorders up until the end of 2005.
14. Logan AC. Neurobehavioural aspects of omega-3 fatty acids: possible mechanisms and therapeutic value in major depression. Alt Med Review 2003; 8:410-425.
15. •].)
16. •].)
17. •].)
18. Bazinet RP, Rao JS, Chang L, et al. Chronic carbamazepine decreases the incorporation rate and turnover of arachidonic acid but not docosahexaenoic acid in brain phospholipids of the unanesthetized rat: relevance to bipolar disorder. Biol Psychiatry 2006; 59:401-407.
19. Bazinet RP, Weis MT, Rapoport SI, et al. Valproic acid selectively inhibits conversion of arachidonic acid to arachidonoyl-CoA by brain microsomal long-chain fatty acyl-CoA synthetases: relevance to bipolar disorder. Psychopharmacology 2006; 184:122-129.
20. Chang MC, Grange E, Rabin O, et al. Lithium decreases turnover of arachidonate in several brain phospholipids. Neurosci Lett 1996; 220:171-174.
21. Freeman MP, Hibbeln JR, Wisner KL, et al. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry 2006; 67:1954-1967. This recent review included a meta-analysis of omega-3 supplementation as a treatment for mood disorders and schizophrenia. The authors found a significant benefit for mood disorders but not schizophrenia. Note that the clinical trial results were highly heterogeneous, limiting the ability to draw overall conclusions from the meta-analysis.
22. Bhattacharya A, Sun D, Rahman M, et al. Different ratios of eicosapentaenoic and docosahexaenoic omega-3 fatty acids in commercial fish oils differentially alter pro-inflammatory cytokines in peritoneal macrophages from C57BL/6 female mice. J Nutr Biochem 2007; 18:23-30. This is one of the few studies to compare directly the effects of different ratios of EPA to DHA. The authors found that, compared with corn oil control, a diet with a 2:1 ratio of EPA to DHA produced a significant reduction in inflammatory cytokines in female mice. Two other omega-3 diets with lower ratios of EPA to DHA had lesser impacts on cytokine levels.
23. Kiecolt-Glaser JK, Belury MA, Porter K, et al. Depressive symptoms, omega-6: omega-3 fatty acids, and inflammation in older adults. Psychosom Med 2007; 69:217-224. The authors of this study demonstrated an interaction between depressive symptoms and plasma omega-6 : omega-3 ratio on inflammatory cytokines.
24. Rees AM, Austin MP, Parker G. The role of omega-3 fatty acids as a treatment for depression in the perinatal period. Aust NZ J Psychiatry 2005; 39:274-280.
25. Levant B, Ozias MK, Carlson SE. Specific brain regions of female rats are differentially depleted of docosahexaenoic acid by reproductive activity and an (n-3) fatty acid-deficient diet. J Nutr 2007; 137:130-134. The authors found that low dietary intake and reproductive activity on their own did not lead to a significant reduction in DHA levels in the brains of female rats but that the combination of the two did.
26. Cundiff DK, Lanou AJ, Nigg CR. Relation of omega-3 fatty acid intake to other dietary factors known to reduce coronary heart disease risk. Am J Cardiol 2007; 99:1230-1233. This is an important cautionary article for those conducting and interpreting case-control studies into the association between omega-3 levels and conditions such as cardiac disease and depression. The authors found that omega-3 consumption correlated significantly with a variety of other dietary factors, indicating that the benefits associated with higher omega-3 levels may in fact be due to the general benefits of a healthier diet.
27. McNamara RK, Hahn C-G, Jandacek R, et al. Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder. Biol Psychiatry 2007; 62:17-24. This is the first study to measure omega-3 levels in the brains of depressed patients. Those with depression had lower levels of DHA in the postmortem orbitofrontal cortex.
28. Conklin SM, Gianaros PJ, Brown SM, et al. Long-chain omega-3 fatty acid intake is associated positively with corticolimbic gray matter volume in healthy adults. Neurosci Lett 2007; 421:209-212. In this structural magnetic resonance imaging study, dietary intake of omega-3 correlated with grey matter volume in areas of the brain associated with mood disorders (amygdala, hippocampus and anterior cingulate cortex).
29. Huan M, Hamazaki K, Sun Y, et al. Suicide attempt and n-3 fatty acid levels in red blood cells: a case control study in China. Biol Psychiatry 2004; 56:490-496.
30. Sublette ME, Hibbeln JR, Galfalvy H, et al. Omega-3 polyunsaturated essential fatty acid status as a predictor of future suicide risk. Am J Psychiatry 2006; 163:1100-1102. This case-control study found that omega-3 levels and omega-6: omega-3 ratio predicted suicide attempts over the following 2 years. Strengths of the study include the prospective design and the fact that the authors controlled for a variety of confounding demographic factors.
31. Glassman AH, Shapiro PA. Depression and the course of coronary artery disease. Am J Psychiatry 1998; 155:4-111.
32. Severus WE, Ahrens B. Stoll AL: Omega-3 fatty acids-the missing link? (letter). Arch Gen Psychiatry 1999; 56:380-381.
33. Frasure-Smith N, Lesperance 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.
34. Parker GB, Heruc GA, Hilton TM, et al. Low levels of docosahexaenoic acid identified in acute coronary syndrome patients with depression. Psychiatry Res 2006; 141:279-286. Clinically depressed patients admitted to hospital for an acute coronary event had lower levels of plasma phospholipid DHA than did their nondepressed counterparts.
35. Schins A, Crijns HJ, Brummer RJM, et al. Altered omega-3 polyunsaturated fatty acid status in depressed postmyocardial infarction patients. Acta Psychiatr Scand 2007; 115:35-40. Depressed post-myocardial infarction patients had significantly lower ratios of EPA to arachidonic acid than did their nondepressed counterparts.
36. 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-3PUFAs are related to major depression. Life Sci 2003; 73:3181-3187.
37. 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.
38. Miyake Y, Sasaki S, Yokoyama T, et al. 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.
39. Nemets H, Nemets B, Apter A, et al. Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry 2006; 163:1098-1100. This small but important clinical trial provides the first evidence that omega-3 supplementation may be an effective monotherapy for childhood depression. This is particularly noteworthy, given the current concerns about the safety and efficacy of traditional antidepressants for childhood depression.
40. Whittington CJ, Kendall T, Pilling S. Are the SSRIs and atypical antidepressants safe and effective for children and adolescents? Curr Opin Psychiatry 2005; 18:21-25.
41. Hallahan B, Hibbeln JR, Davis JM, et al. Omega-3 fatty acid supplementation in patients with recurrent self-harm. Single-centre double-blind randomised controlled trial. Br J Psychiatry 2007; 190:118-122. This trial suggests that omega-3 supplementation can improve depression, suicidality and perceived stress in patients with recurrent self-harm, which is consistent with the previous study carried out by Zanarini and Frankenburg [9] of omega-3 for patients with borderline personality disorder patients.
42. 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.
43. Keck PE Jr, Mintz J, McElroy SL, 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. This is a large, well controlled, randomized controlled trial conducted by investigators at the Stanley Bipolar Institute, which found absolutely no benefit of 6g/day EPA supplementation as an adjunct treatment for bipolar disorder or rapid cycling bipolar disorder.
44. Frangou S, Lewis M, McCrone P. Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Br J Psychiatry 2006; 188:46-50. In marked contrast to the Stanley Institute's finding above, this smaller clinical trial found a significant improvement in depression score and general functioning in patients who received a relatively low dose of EPA in addition to their usual treatment, compared with control individuals.
45. Austin MP. To treat or not to treat: maternal depression, SSRI use in pregnancy and adverse neonatal effects. Psychol Med 2006; 36:1663-1670.
46. Freeman MP, Hibbeln JR, Wisner KL, et al. Randomized dose-ranging pilot trial of omega-3 fatty acids for postpartum depression. Acta Psychiatr Scand 2006; 113:31-35.