Nutrition, psychoneuroimmunology and depression: the therapeutic implications of omega-3 fatty acids in interferon-α-induced depression

Belmaker RH, Agam G. Major depressive disorder. N Engl J Med 2008; 358: 55–68. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 1997; 349: 1498–504. Hasler G, Drevets WC, Manji HK, Charney DS. Discovering endophenotypes for major depression. Neuropsychopharmacology 2004; 29: 1765–81. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006; 27: 24–31. Su KP, Huang SY, Peng CY, Lai HC, Huang CL, Chen YC, et al. Phospholipase A2 and Cyclooxygenase 2 Genes Influence the Risk of Interferon-alpha-Induced Depression by Regulating Polyunsaturated Fatty Acids Levels. Biol Psychiatry 2010; 67: 550–7. Su KP. Inflammation in psychopathology of depression: Clinical, biological, and therapeutic implications. BioMedicine 2012; 2: 68–74. Maes M, Leonard B, Fernandez A, Kubera M, Nowak G, Veerhuis R, et al. (Neuro)inflammation and neuroprogression as new pathways and drug targets in depression: from antioxidants to kinase inhibitors. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 659–63. Danese A, Moffitt TE, Pariante CM, Ambler A, Poulton R, Caspi A. Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Arch Gen Psychiatry 2008; 65: 409–15. Danese A, Pariante CM, Caspi A, Taylor A, Poulton R. Childhood maltreatment predicts adult inflammation in a life-course study. Proc Natl Acad Sci USA 2007; 104: 1319–24. Su KP. Biological Mechanism of Antidepressant Effect of Omega-3 Fatty Acids: How Does Fish Oil Act as a ‘Mind-Body Interface’? Neurosignals 2009; 17: 144–52. Hibbeln JR, Nieminen LR, Blasbalg TL, Riggs JA, Lands WE. Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity. Am J Clin Nutr 2006; 83: 1483S–93S. Lin PY, Huang SY, Su KP. A meta-analytic review of polyunsaturated fatty acid compositions in patients with depression. Biol Psychiatry 2010; 68: 140–7. McNamara RK, Hahn CG, Jandacek R, Rider T, Tso P, Stanford KE, 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. 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: 3181–7. 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: 107–13. Chiu CC, Huang SY, Su KP, Lu ML, Huang MC, Chen CC, et al. Polyunsaturated fatty acid deficit in patients with bipolar mania. Eur Neuropsychopharmacol 2003; 13: 99–103. 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: 1577–84. Freeman MP, Mischoulon D, Tedeschini E, Goodness T, Cohen LS, Fava M, et al. Complementary and alternative medicine for major depressive disorder: a meta-analysis of patient characteristics, placebo-response rates, and treatment outcomes relative to standard antidepressants. J Clin Psychiatry 2010; 71: 682–8. Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, et al. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry 2006; 67: 1954–67. Lin PY, Mischoulon D, Freeman MP, Matsuoka Y, Hibbeln J, Belmaker RH, et al. Are omega-3 fatty acids antidepressants or just mood-improving agents? The effect depends upon diagnosis, supplement preparation, and severity of depression. Mol Psychiatry 2012; 17: 1161–3. Lin PY, Su KP. A meta-analytic review of double-blind, placebocontrolled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry 2007; 68: 1056–61. Martins JG, Bentsen H, Puri BK. Eicosapentaenoic acid appears to be the key omega-3 fatty acid component associated with efficacy in major depressive disorder: a critique of Bloch and Hannestad and updated meta-analysis. Mol Psychiatry 2012; 17: 1144–9. 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: 1308–16. Bloch MH, Hannestad J. Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis. Mol Psychiatry 2012; 17: 1272–82. Appleton KM, Rogers PJ, Ness AR. Is there a role for n-3 longchain 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. Appleton KM, Rogers PJ, Ness AR. Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood. Am J Clin Nutr 2010; 91: 757–70. 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: 421–31. Ness AR, Gallacher JE, Bennett PD, Gunnell DJ, Rogers PJ, Kessler D, et al. Advice to eat fish and mood: a randomised controlled trial in men with angina. Nutr Neurosci 2003; 6: 63–5. Sarris J, Mischoulon D, Schweitzer I. Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depression. J Clin Psychiatry 2012; 73: 81–6. Chiu CC, Huang SY, Chen CC, Su KP. Omega-3 fatty acids are more beneficial in the depressive phase than in the manic phase in patients with bipolar I disorder. J Clin Psychiatry 2005; 66: 1613–4. Su KP, Shen WW, Huang SY. Are omega3 fatty acids beneficial in depression but not mania? Arch Gen Psychiatry 2000; 57: 716–7. Su KP, Shen WW, Huang SY. The use of omega-3 fatty acids for the management of depression and psychosis during pregnancy and breast-feeding. In: Peet M, Glen I, Horrobin DF, editors. Phospholipid spectrum disorder in psychiatry and neurology. 2 ed. Carnforth: Marius Press; 2003. pp. 391–9. Chiu CC, Huang SY, Shen WW, Su KP. Omega-3 fatty acids for depression in pregnancy. Am J Psychiatry ; 160: 385. 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: 644–51. Freeman MP. Omega-3 fatty acids and perinatal depression: a review of the literature and recommendations for future research. Prostaglandins Leukot Essent Fatty Acids 2006; 75: 291–7. Nemets H, Nemets B, Apter A, Bracha Z, Belmaker RH. Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry 2006; 163: 1098–100. Hallahan B, Hibbeln JR, Davis JM, Garland MR. Omega-3 fatty acid supplementation in patients with recurrent self-harm. Singlecentre double-blind randomised controlled trial. Br J Psychiatry 2007; 190: 118–22. Freeman MP, Hibbeln JR, Silver M, Hirschberg AM, Wang B, Yule AM, et al. Omega-3 fatty acids for major depressive disorder associated with the menopausal transition: a preliminary open trial. Menopause 2011; 18: 279–84. 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: 167–9. Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol 2007; 99: 35C–43C. Su KP, Lai HC, Yang HT, Su WP, Peng CY, Chang JP, et al. Omega-3 fatty acids in the prevention of interferon-alpha-induced depression: results from a randomized, controlled trial. Biol Psychiatry 2014; 76: 559–66. Su KP, Wang SM, Pae CU. Omega-3 polyunsaturated fatty acids for major depressive disorder. Expert Opin Investig Drugs 2013; 22: 1519–34. Bays H. Clinical overview of Omacor: a concentrated formulation of omega-3 polyunsaturated fatty acids. Am J Cardiol 2006; 98: 71i- 6i. Harris WS. Expert opinion: omega-3 fatty acids and bleeding-cause for concern? Am J Cardiol 2007; 99: 44C–6C. Kinrys G. Hypomania associated with omega-3 fatty acids. Arch Gen Psychiatry 2000; 57: 715–6. Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA 2010; 303: 47–53. Katon W, Sullivan MD. Depression and chronic medical illness. J Clin Psychiatry 1990; 51 Suppl: 3–11. Su KP. Mind-body interface: the role of n-3 fatty acids in psychoneuroimmunology, somatic presentation, and medical illness comorbidity of depression. Asia Pac J Clin Nutr 2008; 17 Suppl 1: 151–7. Konsman JP, Parnet P, Dantzer R. Cytokine-induced sickness behaviour: mechanisms and implications. Trends Neurosci 2002; 25: 154–9. Smith RS. The macrophage theory of depression. Med Hypotheses 1991; 35: 298–306. Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 2007; 10: 1387–94. Lu DY, Leung YM, Su KP. Interferon-alpha induces nitric oxide synthase expression and haem oxygenase-1 down-regulation in microglia: implications of cellular mechanism of IFN-alpha-induced depression. Int J Neuropsychopharmacol 2013; 16: 433–44. Lu DY, Tsao YY, Leung YM, Su KP. Docosahexaenoic acid suppresses neuroinflammatory responses and induces heme oxygenase-1 expression in BV-2 microglia: implications of antidepressant effects for omega-3 fatty acids. Neuropsychopharmacology 2010; 35: 2238–48. Gozzelino R, Jeney V, Soares MP. Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol 2010; 50: 323–54. Hochstrasser T, Ullrich C, Sperner-Unterweger B, Humpel C. Inflammatory stimuli reduce survival of serotonergic neurons and induce neuronal expression of indoleamine 2,3-dioxygenase in rat dorsal raphe nucleus organotypic brain slices. Neuroscience 2011; 184: 128–38. Song C, Wang H. Cytokines mediated inflammation and decreased neurogenesis in animal models of depression. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 760–8. Zhang F, Zhou H, Wilson BC, Shi JS, Hong JS, Gao HM. Fluoxetine protects neurons against microglial activation-mediated neurotoxicity. Parkinsonism Relat Disord 2012; 18 Suppl 1: S213–S7. Asnis GM, De La GR. Interferon-induced depression in chronic hepatitis C: a review of its prevalence, risk factors, biology, and treatment approaches. J Clin Gastroenterol 2006; 40: 322–35. Bonaccorso S, Puzella A, Marino V, Pasquini M, Biondi M, Artini M, et al. Immunotherapy with interferon-alpha in patients affected by chronic hepatitis C induces an intercorrelated stimulation of the cytokine network and an increase in depressive and anxiety symptoms. Psychiatry Res 2001; 105: 45–55. Raison CL, Borisov AS, Majer M, Drake DF, Pagnoni G, Woolwine BJ, et al. Activation of central nervous system inflammatory pathways by interferon-alpha: relationship to monoamines and depression. Biol Psychiatry 2009; 65: 296–303. Capuron L, Raison CL, Musselman DL, Lawson DH, Nemeroff CB, Miller AH. Association of exaggerated HPA axis response to the initial injection of interferon-alpha with development of depression during interferon-alpha therapy. Am J Psychiatry 2003; 160: 1342–5. Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, et al. Interferon-alpha-induced changes in tryptophan metabolism. relationship to depression and paroxetine treatment. Biol Psychiatry 2003; 54: 906–14. Capuron L, Pagnoni G, Demetrashvili M, Woolwine BJ, Nemeroff CB, Berns GS, et al. Anterior cingulate activation and error processing during interferon-alpha treatment. Biol Psychiatry 2005; 58: 190–6. Bull SJ, Huezo-Diaz P, Binder EB, Cubells JF, Ranjith G, Maddock C, et al. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferonalpha and ribavirin treatment. Mol Psychiatry 2009; 14: 1145. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med 2001; 345: 41–52. Poynard T, Yuen MF, Ratziu V, Lai CL. Viral hepatitis C. Lancet 2003; 362: 2095–100. Schaefer M, Capuron L, Friebe A, ez-Quevedo C, Robaeys G, Neri S, et al. Hepatitis C infection, antiviral treatment and mental health: a European expert consensus statement. J Hepatol 2012; 57: 1379–90. Dieperink E, Ho SB, Thuras P, Willenbring ML. A prospective study of neuropsychiatric symptoms associated with interferon-alpha-2b and ribavirin therapy for patients with chronic hepatitis C. Psychosomatics 2003; 44: 104–12. Raison CL, Woolwine BJ, Demetrashvili MF, Borisov AS, Weinreib R, Staab JP, et al. Paroxetine for prevention of depressive symptoms induced by interferon-alpha and ribavirin for hepatitis C. Aliment Pharmacol Ther 2007; 25: 1163–74. de Knegt RJ, Bezemer G, Van Gool AR, Drenth JP, Hansen BE, Droogleever Fortuyn HA, et al. Randomised clinical trial: escitalopram for the prevention of psychiatric adverse events during treatment with peginterferon-alfa-2a and ribavirin for chronic hepatitis C. Aliment Pharmacol Ther 2011; 34: 1306–17. Schaefer M, Sarkar R, Knop V, Effenberger S, Friebe A, Heinze L, et al. Escitalopram for the Prevention of Peginterferon-alpha2a-Associated Depression in Hepatitis C Virus-Infected Patients Without Previous Psychiatric Disease: A Randomized Trial. Ann Intern Med 2012; 157: 94–103. Diez-Quevedo C, Masnou H, Planas R, Castellvi P, Gimenez D, Morillas RM, et al. Prophylactic treatment with escitalopram of pegylated interferon alfa-2a-induced depression in hepatitis C: a 12- week, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2011; 72: 522–8. Morasco BJ, Loftis JM, Indest DW, Ruimy S, Davison JW, Felker B, et al. Prophylactic antidepressant treatment in patients with hepatitis C on antiviral therapy: a double-blind, placebo-controlled trial. Psychosomatics 2010; 51: 401–8. Morasco BJ, Rifai MA, Loftis JM, Indest DW, Moles JK, Hauser P. A randomized trial of paroxetine to prevent interferon-alpha-induced depression in patients with hepatitis C. J Affect Disord 2007; 103: 83–90. Hejny C, Sternberg P, Lawson DH, Greiner K, Aaberg TM, Jr. Retinopathy associated with high-dose interferon alfa-2b therapy. Am J Ophthalmol 2001; 131: 782–7. Musselman DL, Lawson DH, Gumnick JF, Manatunga AK, Penna S, Goodkin RS, et al. Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med 2001; 344: 961–6. Loftis JM, Hauser P. Safety of the treatment of interferon-alphainduced depression. Psychosomatics 2003; 44: 524–6. Wu PL, Liao KF, Peng CY, Pariante CM, Su KP. Manic episode associated with citalopram therapy for interferon-induced depression in a patient with chronic hepatitis C infection. Gen Hosp Psychiatry 2007; 29: 374–6. Capuron L, Gumnick JF, Musselman DL, Lawson DH, Reemsnyder A, Nemeroff CB, et al. Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology 2002; 26: 643–52. Song C, Phillips AG, Leonard BE, Horrobin DF. Ethyl-eicosapentaenoic acid ingestion prevents corticosterone-mediated memory impairment induced by central administration of interleukin-1beta in rats. Mol Psychiatry 2004; 9: 630–8. Song C, Leonard BE, Horrobin DF. Dietary ethyl-eicosapentaenoic acid but not soybean oil reverses central interleukin-1-induced changes in behavior, corticosterone and immune response in rats. Stress 2004; 7: 43–54. Mischoulon D, Best-Popescu C, Laposata M, Merens W, Murakami JL, Wu SL, et al. A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major depressive disorder. Eur Neuropsychopharmacol 2008; 18: 639–45. Raison CL, Dantzer R, Kelley KW, Lawson MA, Woolwine BJ, Vogt G, et al. CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression. Mol Psychiatry 2010; 15: 393–403. Cattaneo A, Gennarelli M, Uher R, Breen G, Farmer A, Aitchison KJ, et al. Candidate genes expression profile associated with antidepressants response in the GENDEP study: differentiating between baseline ‘predictors’ and longitudinal ‘targets’. Neuropsychopharmacology 2013; 38: 377–85. Carvalho LA, Torre JP, Papadopoulos AS, Poon L, Juruena MF, Markopoulou K, et al. Lack of clinical therapeutic benefit of antidepressants is associated overall activation of the inflammatory system. J Affect Disord 2013; 148: 136–40. Zunszain PA, Anacker C, Cattaneo A, Choudhury S, Musaelyan K, Myint AM, et al. Interleukin-1beta: a new regulator of the kynurenine pathway affecting human hippocampal neurogenesis. Neuropsychopharmacology 2012; 37: 939–49. Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 2013; 70: 31–41. Bazinet RP, Laye S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci 2014; 15: 771–85. 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. Beltz BS, Tlusty MF, Benton JL, Sandeman DC. Omega-3 fatty acids upregulate adult neurogenesis. NeurosciLett 2007; 415: 154–8. Castren E, Hen R. Neuronal plasticity and antidepressant actions. Trends Neurosci 2013. Eisch AJ, Petrik D. Depression and hippocampal neurogenesis: a road to remission? Science 2012; 338: 72–5. 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: 407–12. Su KP, Balanzá-Martínez V. Role of omega-3 fatty acids in mood disorders. In: McNamara RK, editor. The omega-3 fatty acid deficiency syndrome: opportunities for disease prevention. NY, USA: Nova Science Pub Inc.; 2013. pp. 315–36. Amminger GP, Schafer MR, Papageorgiou K, Klier CM, Cotton SM, Harrigan SM, et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry 2010; 67: 146–54. Matsuoka Y, Nishi D, Yonemoto N, Hamazaki K, Hashimoto K, Hamazaki T. Omega-3 fatty acids for secondary prevention of posttraumatic stress disorder after accidental injury: an open-label pilot study. J Clin Psychopharmacol 2010; 30: 217–9.