Skip to main content

Inflammation, Heart Disease, and Depression

Abstract

Morbidity and mortality of cardiovascular disease is exceedingly high worldwide. Depressive illness afflicts a significant portion of the population worldwide. Epidemiological studies have confirmed the high co-morbidity between these two entities and the co-morbidity is bidirectional. Systems that contribute to this co-morbidity include the central and autonomic nervous systems, the neuroendocrine, immune, vascular and hematologic systems. Specific pathophysiologic factors include imbalance between the sympathetic and the parasympathetic systems, sympathoadrenal activation, hypothalamic-pituitary-adrenal axis activation, immune system dysregulation with release of pro-inflammatory cytokines and chemokines, platelet activation and hypercoaguability. Inflammation occurs in cardiac and cardiovascular pathology independent of the presence or absence of depression and in depression. Inflammation is closely associated with endothelial dysfunction which is a preamble to atherosclerosis and atherothrombosis. A likely common instigator underlying this co-morbidity is mental stress leading to sustained sympathetic overdrive and diminished vagal tone. Diminished vagal tone contributes to a pro-inflammatory status which affects neurotransmitter regulation, specifically serotonergic transmission. Stress hormones and certain pro-inflammatory substances released by macrophages and microglia upregulate the rate-limiting enzymes in the metabolic pathway of tryptophan. This results in a shunt in tryprophan metabolism away from serotonin formation and down the kynurenine pathway with resulting formation of neurotoxic metabolites.

This is a preview of subscription content, access via your institution.

Fig. 1

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Dahlof B. Cardiovascular disease risk factors: epidemiology and risk assessment. Am J Cardiol. 2010;105(1 Suppl):3A–9A.

    Article  PubMed  Google Scholar 

  2. Lloyd-Jones DM, Hong Y, Labarthe D, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction. Circulation. 2010;121(4):586–613.

    Article  PubMed  Google Scholar 

  3. Waldman SA, Terzic A. Cardiovascular health: The global challenge. Clin Pharmacol Therap. 2011;90(4):483–5.

    Article  CAS  Google Scholar 

  4. Terzic A, Waldman SA. Chronic diseases: the emerging pandemic. Clin Transl Sci. 2011;4:225–6.

    Article  PubMed  Google Scholar 

  5. Kovasic JC, Fuster V. From treating complex coronary disease to promoting cardiovascular health: Therapeutic transitions and challenges 2010-2020. Clin Pharmacol Ther. 2011;90(4):509–18.

    Article  CAS  Google Scholar 

  6. Viles-Gonzalez JF, Fuster V, Badimon JJ. Atherothrombosis: A widespread disease with unpredictable and life-threatening consequences. Eur Heart J. 2004;25:1197–207.

    Article  PubMed  CAS  Google Scholar 

  7. American Heart Association. Heart Disease and Stroke Statistics – 2004 update. Dallas, TX: American Heart Association. 2004.

  8. Murray CJ, Lopez AD. Global mortality, disability and the contribution of risk factors: Global Burden of Disease Study. Lancet. 1997;349(9063):1436–42.

    Article  PubMed  CAS  Google Scholar 

  9. Demyttenaere K, Bruffaerts R, Posada-Villa J, et al. Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization world Mental Health surveys. JAMA. 2004;291:2581–90.

    Article  PubMed  Google Scholar 

  10. Centers for Disease Control and Prevention (CDC). Current depression among adults – United states, 2006 and 2008. Morb Mortal Wkly Rep. 2010;59:1229–35.

    Google Scholar 

  11. •• Lepin JP, Briley M. The increasing burden of depression. Neuropsych Dis Treat. 2011;7 Suppl 1:3–7. This article provides a brief overview of how depression affects quality of life and of the increasing burden of depression.

    Google Scholar 

  12. Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation. 1999;99:2192–217.

    Article  PubMed  CAS  Google Scholar 

  13. Barth J, Schumacher M, Herrmann-Lingen C. Depression as a risk factor for mortality in patients with coronary heart disease: a meta-analysis. Psychosom Med. 2004;66:802–13.

    Article  PubMed  Google Scholar 

  14. Gump BB, Matthews KA, Eberly LE, Chang YF, MRFIT Research Group. Depressive symptoms and mortality in men: results from Multiple Risk Factor Intervention Trial. Stroke. 2005;36:98–102.

    Article  PubMed  Google Scholar 

  15. Halaris A. Co-morbidity between depression and cardiovascular disease. Int Angiol. 2009;28(2):92–9.

    PubMed  CAS  Google Scholar 

  16. • Saleptsis VG, Lambropoulos N, Halaris A, Angelopoulos NV, Giannoukas AD. Depression and atherosclerosis. Int Angiol. 2011;30(2):97–104. This is the most recent review of this topic.

    PubMed  CAS  Google Scholar 

  17. Fielding R. Depression and acute myocardial infarction: A review and reinterpretation. Soc Sci Med. 1991;32:1017–27.

    Article  PubMed  CAS  Google Scholar 

  18. Schleifer SJ, Macari-Hinson MM, Coyle DA. The nature and course of depression following myocardial infarction. Arch Intern Med. 1989;149:1785–9.

    Article  PubMed  CAS  Google Scholar 

  19. Frasure-Smith N, Lesperance F, Talajic M. Depression following myocardial infarction: impact of 6-month survival. JAMA. 1993;270:1819–25.

    Article  PubMed  CAS  Google Scholar 

  20. Frasure-Smith N, Lesperance F, Talajic M. Depression and 18-month prognosis after myocardial infraction. Circulation. 1995;91:999–1005.

    Article  PubMed  CAS  Google Scholar 

  21. Lesperance F, Frasure-Smith N, Jueau M, Theroux P. Depression and 1-year prognosis in unstable angina. Arch Intern Med. 2000;160:1354–60.

    Article  PubMed  CAS  Google Scholar 

  22. Ahern DK, Gorkin L, Anderson JL, Tierney C, Hallstrom A, Ewart C, et al. Biobehavioral variables and mortality or cardiac arrest in the Cardiac Arrhythmia Pilot Study (CAPS). Am J Cardiol. 1990;66:59–62.

    Article  PubMed  CAS  Google Scholar 

  23. Bush DE, Ziegelstein RC, Tayback M, Richter D, Stevens S, Zahalsky H, et al. Even minimal symptoms of depression increase mortality risk after acute myocardial infection. Am J Cardiol. 2001;88:337–41.

    Article  PubMed  CAS  Google Scholar 

  24. Ford DE, Mead LA, Chang PP. Depression is a risk factor for coronary artery disease in men: the precursors study. Arch Intern Med. 1998;158(13):1422–26.

    Article  PubMed  CAS  Google Scholar 

  25. Ariyo AA, Haan M, Tangen CM, Ruteledge JC, Cushman M, Dobs A. Depressive symptoms and risks of coronary heart disease and mortality in elderly Americans. Cardiovascular Health Study Collaborative Research Group Circulation. 2000;102:1773–79.

    CAS  Google Scholar 

  26. Penninx BW, Beekman AT, Honig A, Deeg DJ, Schoevers RA, van Eijk JT. Depression and cardiac mortality: Results from a community-based longitudinal study. Arch Gen Psychiatry. 2001;58:221–7.

    Article  PubMed  CAS  Google Scholar 

  27. Jiang W, Alexander J, Christopher E, Kuchibhatia M, Gaulden LH, Cuffe MS. Relationship of depression to increased risk of mortality and rehospitalization in patients with congestive heart failure. Arch Intern Med. 2001;161:1849–56.

    Article  PubMed  CAS  Google Scholar 

  28. Lesperance J, Frasure-Smith N, Talajic M, Bourassa M. Five-year risk of cardiac mortality in relation to initial severity and one-year changes in depression symptoms in myocardial infarction. Circulation. 2002;105:1049–53.

    Article  PubMed  Google Scholar 

  29. Junger J, Schellberg D, Muller-Tasch T. Depression increasingly predicts mortality in the course of congestive heart failure. Eur J Heart Fail. 2005;7:261–7.

    Article  PubMed  Google Scholar 

  30. Sherwood A, Blumenthal JA, Trivedi R, et al. Relationship of depression to death or hospitalization in patients with heart failure. Arch Intern Med. 2007;167:367–73.

    Article  PubMed  Google Scholar 

  31. Eaton WW, Fogel J, Armenian HK. The consequences of psychopathology in the Baltimore Epidemiologic Catchment Area Follow-up. Medical and Psychiatric Co-morbidity over the Lifespan. Washington: American Psychiatric. 2006; pp 21–38.

  32. Wulsin LR, Evans JC, Vasan RS, Murabito JM, Kelly-Hayes M, Benjamin E. Depressive symptoms, coronary heart disease, and overall mortality in the Framingham Heart Study. Psychosom Med. 2005;67:697–702.

    Article  PubMed  Google Scholar 

  33. Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to cardiovascular disease: Epidemiology, biology, and treatment. Arch Gen Psychiatry. 1998;55:580–92.

    Article  PubMed  CAS  Google Scholar 

  34. O’Connor CM, Gurbel PA, Serebruany VL. Depression in ischemic heart disease. Am Heart J. 2000;140:63–9.

    Article  PubMed  Google Scholar 

  35. Carney RM, Jaffe AS. Treatment of depression following acute myocardial infarction. JAMA. 2002;288:750–1.

    Article  PubMed  Google Scholar 

  36. Nicholson A, Kuper H, Hemingway H. Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies. Eur Heart J. 2006;27:2763–74.

    Article  PubMed  Google Scholar 

  37. Thayer JF, Lane RD. The role of vagal function in the risk for cardiovascular disease and mortality. Biol Psychol. 2007;74:224–42.

    Article  PubMed  Google Scholar 

  38. Otte C, Neylan TC, Pipkin SS, Browner WS, Whooley MA. Depressive symptoms and 24-hour urinary norepinephrine excretion levels in patients with coronary disease: findings from the Heart and Soul Study. Am J Psychiatry. 2005;162(11):2139–45.

    Article  PubMed  Google Scholar 

  39. Licht CMM, de Geus EJC, Zitman FG, Hoogendijk WJG, van Dyck R, Penninx BWJH. Association between major depressive disorder and heart rate variability in the Netherlands study of depression and anxiety (NESDA). Arch Gen Psychiat. 2008;65912:1358–67.

    Article  Google Scholar 

  40. Porges SW. The polyvagal theory: phylogenetic substrates of a social nervous system. Int J Psychophysiol. 2001;42(2):123–46.

    Article  PubMed  CAS  Google Scholar 

  41. Porges SW. Cardiac vagal tone; a physiological index of stress. Neurosci Biobehav Rev. 1995;19(2):225–33.

    Article  PubMed  CAS  Google Scholar 

  42. Porges SW. Emotion: an evolutionary by-product of the neural regulation of the autonomic nervous system. Ann NY Acad Sci. 1997;807:62–77.

    Article  PubMed  CAS  Google Scholar 

  43. Ross R. Atherosclerosis-an inflammatory disease. New Engl J Med. 1999;340:115–26.

    Article  PubMed  CAS  Google Scholar 

  44. Lind L. Circulating markers of inflammation and atherosclerosis. Atherosclerosis. 2003;169:203–14.

    Article  PubMed  CAS  Google Scholar 

  45. Frasure-Smith N, Lespérance F, Irwin MR, Sauvé C, Lespérance J, Théroux P. Depression, C-reactive protein and two-year major adverse cardiac events in men after acute coronary syndromes. Biol Psychiatry. 2007;62(4):302–8.

    Article  PubMed  CAS  Google Scholar 

  46. Hansson G. Inflammation, atherosclerosis, and coronary artery disease. New Engl J Med. 2005;352(16):1685–95.

    Article  PubMed  CAS  Google Scholar 

  47. Seta Y, Shan K, Bozkurt B, et al. Basic mechanisms in heart failure: the cytokine hypothesis. J Card Fail. 1996;2:243–9.

    Article  PubMed  CAS  Google Scholar 

  48. Petersen JW, Felker M. Inflammatory biomarkers in heart failure. Congest Heart Fail. 2006;12(6):324–8.

    Article  PubMed  CAS  Google Scholar 

  49. Maes M, Bosmans E, Suy E, Vandervorst C, DeJonckheere C, Raus J. Depression-related disturbances in mitogen-induced lymphocyte responses and interleukin-1 beta and soluble interleukin-2 receptor production. Acta Psychiat Scand. 1991;84:379–86.

    Article  PubMed  CAS  Google Scholar 

  50. Maes M. Evidence for an immune response in major depression: a review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry. 1995;19:11–38.

    Article  PubMed  CAS  Google Scholar 

  51. Wichers M, Maes M. The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans. Int J Neuropsychopharmacol. 2002;5:375–88.

    Article  PubMed  CAS  Google Scholar 

  52. Lee KM, Kim YK. The role of IL-12 and TGF-beta1 in the pathophysiology of major depressive disorder. Int Immunopharmacol. 2006;6:1298–304.

    Article  PubMed  CAS  Google Scholar 

  53. Koenig W. Inflammation and coronary heart disease: An overview. Cardiol Rev. 2001;9:31–5.

    Article  PubMed  CAS  Google Scholar 

  54. Mulvihill NT, Foley JB. Inflammation in acute coronary syndromes. Heart. 2002;87:201–4.

    Article  PubMed  CAS  Google Scholar 

  55. Robbins M, Topol EJ. Inflammation in acute coronary syndromes. Cleve Clin J Med. 2002;69 Suppl 2:SII130–42.

    Article  PubMed  Google Scholar 

  56. Maes M, Bosmans E, Meltzer HY, Scharpe S, Suy E. Interleukin-1 beta: A putative mediator of HPA axis hyperactivity in major depression? Am J Psychiatry. 1993;150:1189–93.

    PubMed  CAS  Google Scholar 

  57. Maes M, der Planken V, Van Gastel A, Desnyder R. Blood coagulation and platelet aggression in major depression. J Affect Disord. 1996;40:35–40.

    Article  PubMed  CAS  Google Scholar 

  58. Kop WJ, Gottdiener JS, Tangen CM, Fried LP, McBurnie MA, Walston J. Inflammation and coagulation factors on persons > 65 years of age with symptoms of depression but without evidence of myocardial ischemia. Am J Cardiol. 2002;89:419–24.

    Article  PubMed  CAS  Google Scholar 

  59. Musselman DL, Miller AH, Porter MR, Manatunga A, Gao F, Penna S. Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am J Psychiatry. 2001;158:1252–7.

    Article  PubMed  CAS  Google Scholar 

  60. Connor TJ, Leonard BE. Depression, stress and immunological activation: the role of cytokines in depressive disorders. Life Sci. 1998;62:583–606.

    Article  PubMed  CAS  Google Scholar 

  61. Leonard BE. Brain cytokines and the psychopathology of depression. In: Leonard BE, editor. Antidepressants. Basel: Birkhauser Verlag; 2001. p. 109–20.

    Chapter  Google Scholar 

  62. Castanon N, Leonard BE, Neveu PJ, Yirmiya R. Effects of antidepressants on cytokine production and actions. Brain Behav Immun. 2002;16:569–74.

    Article  PubMed  CAS  Google Scholar 

  63. Leonard BE, Myint A. Inflammation and depression: Is there a causal connection with dementia? Neutox Res. 2006;10:149–60.

    CAS  Google Scholar 

  64. von Känel R, Hepp U, Kraemer B, Traber R, Keel M, Mica L, et al. Evidence for low-grade systemic proinflammatory activity in patients with posttraumatic stress disorder. J Psychiatr Res. 2006;41:744–52.

    Article  Google Scholar 

  65. Empana JP, Sykes DH, Luc G, Juhan-Vague I, Arveiler D, Ferrieres J, et al. Contributions of depressive mood and circulating inflammatory markers to coronary heart disease in healthy European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulation. 2005;111:2299–305.

    Article  PubMed  CAS  Google Scholar 

  66. Anda R, Williamson D, Jones D, Macera C, Eaker E, Glassman A, et al. Depressed affect, hopelessness, and the risk of ischemic heart disease in a cohort of U.S. adults. Epidemiology. 1993;4:285–94.

    Article  PubMed  CAS  Google Scholar 

  67. Kamphuis MH, Kalmijn S, Tijhuis MA, Geerlings MI, Giampaoli S, Nissinen A, et al. Depressive symptoms as risk factor of cardiovascular mortality in older European men: the Finland, Italy and Netherlands Elderly (FINE) study. Eur J Cardiovasc Prev Rehabil. 2006;13:199–206.

    Article  PubMed  Google Scholar 

  68. Pratt LA, Ford DE, Crum RM, Armenian HK, Gallo JJ, Eaton WW. Depression, psychotropic medication, and risk of myocardial infarction. Prospective data from the Baltimore ECA follow-up. Circulation. 1996;94:3123–9.

    Article  PubMed  CAS  Google Scholar 

  69. Di Iorio A, Ferrucci L, Sparvieri E, Cherubini A, Volpato S, Corsi A, et al. Abate, Paganelli R. Serum IL-1beta levels in health and disease: a population-based study. 'The InCHIANTI study'. Cytokine. 2003;22:198–205.

    Article  PubMed  CAS  Google Scholar 

  70. Biasucci LM. CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: clinical use of inflammatory markers in patients with cardiovascular diseases: a background paper. Circulation. 2004;110:e560–7.

    Article  PubMed  Google Scholar 

  71. Maes M. Introduction to the special section. Int J Neuropsychopharmacol. 2002;5:329–31.

    Article  PubMed  CAS  Google Scholar 

  72. Dantzer R. Cytokine-induced sickness behavior: mechanisms and implications. Ann N Y Acad Sci. 2001;933:222–34.

    Article  PubMed  CAS  Google Scholar 

  73. Vollmer-Conna U, Fazou C, Cameron B, Li H, Brennan C, Luck L, et al. Production of pro-inflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans. Psychol Med. 2004;34:1289–97.

    Article  PubMed  CAS  Google Scholar 

  74. Smith RS. The macrophage theory of depression. Med Hypotheses. 1991;35(4):298–306.

    Article  PubMed  CAS  Google Scholar 

  75. Ur E, White PD, Grossman A. Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome. Eur Arch Psychiatry Clin Neurosci. 1992;241(5):317–22.

    Article  PubMed  CAS  Google Scholar 

  76. Lett HS, Blumenthal JA, Babyak MA, Sherwood A, Strauman T, Robins C, et al. Depression as a risk factor for coronary artery disease: evidence, mechanisms, and treatment. Psychosom Med. 2004;66:305–15.

    Article  PubMed  Google Scholar 

  77. Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacol. 2000;22:370–9.

    Article  CAS  Google Scholar 

  78. Kubera M, Lin AH, Kenis G, Bosmans E, van Bockstaele D, Maes M. Anti-inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. J Clin Psychopharmacol. 2001;21:199–206.

    Article  PubMed  CAS  Google Scholar 

  79. Kubera M, Kenis G, Bosmans E, Kajta M, Basta-Kaim A, Scharpe S, et al. Stimulatory effect of antidepressants on the production of IL-6. Int Immunopharmacol. 2004;4:185–92.

    Article  PubMed  CAS  Google Scholar 

  80. Kenis G, Maes M. Effects of antidepressants on the production of cytokines. Int J Neuropsychopharmacol. 2002;5:401–12.

    Article  PubMed  CAS  Google Scholar 

  81. Himmerich H, Binder EB, Künzel HE, Schuld A, Lucae S, Uhr M, et al. Successful antidepressant therapy restores the disturbed interplay between TNF-alpha system and HPA axis. Biol Psychiatry. 2006;60:882–8.

    Article  PubMed  CAS  Google Scholar 

  82. Mayer B, Holmer SR, Hengstenberg C, Lieb W, Pfeifer M, Schunkert H. Functional improvement in heart failure patients treated with beta-blockers is associated with a decline of cytokine levels. Int J Cardiol. 2005;103:182–6.

    Article  PubMed  Google Scholar 

  83. Janssen DG, Caniato RN, Verster JC, Baune BT. A psychoneuroimmunological review on cytokines involved in antidepressant treatment response. Human Psychopharmacol. 2010;25:201–15.

    Article  CAS  Google Scholar 

  84. Müller N, Schwarz MJ, Dehning S, Douhe A. Cerovecki Aet al. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry. 2006;11:680–4.

    Article  PubMed  CAS  Google Scholar 

  85. Cleland SJ, Sattar N, Petrie JR, Forouhi NG, Elliott HL, Connell JMC. Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. Clin Sci. 2000;98:531–5.

    Article  PubMed  CAS  Google Scholar 

  86. Piletz JE, Halaris A, Iqbal O, et al. Pro-inflammatory biomarkers in depression: treatment with venlafaxine. World J Biol Psychiatry. 2009;10:313–23.

    Article  PubMed  Google Scholar 

  87. Dinan TG. Inflammatory markers in depression. Curr Opin Psychiatry. 2008;22:32–6.

    Article  Google Scholar 

  88. Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat rev Neurosci. 2008;9(1):46–56.

    Article  PubMed  CAS  Google Scholar 

  89. Leonard BE. The concept of depression as a dysfunction of the immune system. Curr Immunol Rev. 2010;6(3):205–12.

    Article  PubMed  CAS  Google Scholar 

  90. Yoshizumi M, Perella MA, Burnett JC, Lee ME. Circ Res. 1991;73(1):205–9.

    Article  Google Scholar 

  91. Tucci M, Quatraro C, Frassanito MA, Silvestris F. Deregulated expression of monocyte chemoattractant protein-1 (MCP-1) in arterial hypertension: role in endothelial inflammation and atheromasia. J Hypertens. 2006;24:1307–18.

    Article  PubMed  CAS  Google Scholar 

  92. Verma S, Buchanan MR, Anderson TJ. Endothelial function testing as a biomarker of vascular disease. Circulation. 2003;108:2054–9.

    Article  PubMed  Google Scholar 

  93. Rybakowski JK, Wykretowicz A, Heymann-Szlachcinska A, Wysocki H. Impairment of endothelial function in unipolar and bipolar depression. Biol Psychiatry. 2006;60:889–91.

    Article  PubMed  CAS  Google Scholar 

  94. Broadley AJ, Korszun A, Jones CJ, Frenneaux MP. Arterial endothelial function is impaired in treated depression. Heart. 2002;88:521–23.

    Article  PubMed  CAS  Google Scholar 

  95. Mendelson SD. The current status of the platelet 5-HT (2A) receptor in depression. J Affect Disord. 2000;57:13–24.

    Article  PubMed  CAS  Google Scholar 

  96. Hrdina PD, Bakish D, Chudzik J, Ravindran A, Lapierre YD. Serotonergic markers in platelets of patients with major depression: upregulation of 5-HT2 receptors. J Psychiat Neurosci. 1995;20:11–9.

    CAS  Google Scholar 

  97. Neuger J, El Khoury A, Kjellman BF, Wahlund B, Aberg-Wistedt A, Stain-Malgren R. Platelet serotonin functions in untreated major depression. Psychiatry Res. 1999;85:189–98.

    Article  PubMed  CAS  Google Scholar 

  98. Shimbo D, Child J, Davidson K, Geer E, Osende JI, Reddy S, et al. Exaggerated serotonin-mediated platelet reactivity as a possible link in depression and acute coronary syndromes. Am J Cardiol. 2002;89:331–3.

    Article  PubMed  CAS  Google Scholar 

  99. Whyte EM, Pollock BG, Wagner WR, Mulsant BH, Ferrell RE, Mazumdar S, et al. Influence of serotonin-transporter-linked promoter region polymorphism on platelet activation in geriatric depression. Am J Psychiatry. 2001;158:2074–76.

    Article  PubMed  CAS  Google Scholar 

  100. Palazzolo DL, Quadri SK. Interleukin-1 inhibits serotonin release from the hypothalamus in vitro. Life Sci. 1992;51:1797–802.

    Article  PubMed  CAS  Google Scholar 

  101. Zhu CB, Blakely RD, Hewlett WA. The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters. Neuropsychopharmacol. 2006;31:2121–31.

    CAS  Google Scholar 

  102. •• Christmas DM, Potokar JP, Davies SJC. A biological pathway linking inflammation and depression: activation of indoleamine 2,3-dioxygenase. Neurpsych Dis Treat. 2011;7:431–9.

    CAS  Google Scholar 

  103. Myint AM, Kim YK, Verkerk R, Scharpé S, Steinbusch HWM, Leonard BE. Kynurenine pathway in Major Depression: Evidence of impaired neuroprotection. J Affect Disord. 2007;89(1):143–51.

    Article  CAS  Google Scholar 

  104. Myint AH, Kim YK. Cytokine-serotonin interaction through IDO; a neurodegeneration hypothesis of depression. Med Hypotheses. 2003;61(5–6):519–25.

    Article  PubMed  CAS  Google Scholar 

  105. Miller CL, Llenos IC, Dulay JR, Weis S. Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder. Brain Res. 2006;1073–1074:25–37.

    Article  PubMed  CAS  Google Scholar 

  106. Myint AM, Kim YK, Verkerk R, Park SH, Scharpe S, Steinbusch HW, et al. Tryptophan breakdown pathway in bipolar mania. J Affect Disord. 2007;102(1–3):65–72.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was partially supported by an intramural grant by Loyola University Chicago Stritch School of Medicine.

Compliance with ethics Guidelines

Conflict of Interest

Angelos Halaris declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Angelos Halaris.

Additional information

This article is part of the Topical Collection on Complex Medical-Psychiatric Issues

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Halaris, A. Inflammation, Heart Disease, and Depression. Curr Psychiatry Rep 15, 400 (2013). https://doi.org/10.1007/s11920-013-0400-5

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11920-013-0400-5

Keywords