Skip to main content
SpringerLink
Log in

Inflammation-Associated Co-morbidity Between Depression and Cardiovascular Disease

  • Chapter
  • First Online:
Inflammation-Associated Depression: Evidence, Mechanisms and Implications

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 31))

Abstract

Morbidity and mortality of cardiovascular disease (CVD) is exceedingly high worldwide. Depressive illness is a serious psychiatric illness that afflicts a significant portion of the world population. Epidemiological studies have confirmed the high co-morbidity between these two disease entities. The co-morbidity is bidirectional and the mechanisms responsible for it are complex and multifaceted. In addition to genetic, biological systems, psychosocial, and behavioral factors that are involved include the central and autonomic nervous systems, the neuroendocrine, immune, and the vascular and hematologic systems. Specific pathophysiologic factors across these systems include homeostatic imbalance between the sympathetic and the parasympathetic systems with loss of heart rate variability (HRV) in depression, sympathoadrenal activation, hypothalamic–pituitary–adrenal (HPA) axis activation, immune system dysregulation resulting in a pro-inflammatory status, platelet activation, and endothelial dysfunction. These abnormalities have been demonstrated in most individuals diagnosed with major depressive disorder (MDD), bipolar disorder (BPD), and probably in other psychiatric disorders. A likely common instigator underlying the co-morbidity between cardiovascular pathology and depression is mental stress. Chronic stress shifts the homeostatic balance in the autonomic nervous system with sustained sympathetic overdrive and diminished vagal tone. Diminished vagal tone contributes to a pro-inflammatory status with associated sequelae. Stress hormones and certain pro-inflammatory substances released by macrophages and microglia upregulate the rate-limiting enzymes in the metabolic pathway of tryptophan (TRP). This enzymatic upregulation stimulates the kynurenine (KYN) pathway resulting in the formation of neurotoxic metabolites. Inflammation occurs in cardiac, cardiovascular, and cerebrovascular pathology independent of the presence or absence of depression. Inflammation is closely associated with endothelial dysfunction, a preamble to atherosclerosis and atherothrombosis. Endothelial dysfunction has been detected in depression and may prove to be a trait marker for this illness. Thus understanding vascular biology in conjunction with psychiatric co-morbidity will be of critical importance. Antidepressant drug therapy is of definite benefit to patients with medical and psychiatric co-morbidity and may reverse the pro-inflammatory status associated with depression. There is, however, an urgent need to develop novel pharmacotherapeutic approaches to benefit a much larger proportion of patients suffering from these disease entities.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  3. Waldman SA, Terzic A (2011) Cardiovascular health: the global challenge. Clin Pharmacol Ther 90(4):483–485

    Article  CAS  PubMed  Google Scholar 

  4. American Heart Association (2004) Heart disease and stroke statistics. American Heart Association, Dallas, TX

    Google Scholar 

  5. Lepin JP, Briley M (2011) The increasing burden of depression. Neuropsychiatr Dis Treat 7(Suppl 1):3–7

    Google Scholar 

  6. Dantzer R, O’Connor JC, Freund GG et al (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9(1):46–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dinan TG (2008) Inflammatory markers in depression. Curr Opin Psychiatry 22:32–36

    Article  Google Scholar 

  8. Haroon E, Raison CL, Miller AH (2012) Psychoneuroimmunology Meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacol Rev 37:137–162

    Article  CAS  Google Scholar 

  9. Leonard BE (2010) The concept of depression as a dysfunction of the immune system. Curr Immunol Rev 6(3):205–212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Koenig W (2001) Inflammation and coronary heart disease: an overview. Cardiol Rev 9:31–35

    Article  CAS  PubMed  Google Scholar 

  11. Mulvihill NT, Foley JB (2002) Inflammation in acute coronary syndromes. Heart 87:201–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Robbins M, Topol EJ (2002) Inflammation in acute coronary syndromes. Cleve Clin J Med 69(Suppl 2):SII130–SII142

    PubMed  Google Scholar 

  13. Kop WJ, Gottdiener JS, Tangen CM et al (2002) Inflammation and coagulation factors on persons > 65 years of age with symptoms of depression but without evidence of myocardial ischemia. Am J Cardiol 89:419–424

    Article  CAS  PubMed  Google Scholar 

  14. Maes M, Bosmans E, Meltzer HY et al (1993) Interleukin-1 beta: a putative mediator of HPA axis hyperactivity in major depression? Am J Psychiatry 150:1189–1193

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  16. Musselman DL, Miller AH, Porter MR et al (2001) Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am J Psychiatry 158:1252–1257

    Article  CAS  PubMed  Google Scholar 

  17. Castanon N, Leonard BE, Neveu PJ, Yirmiya R (2002) Effects of antidepressants on cytokine production and actions. Brain Behav Immun 16:569–574

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Leonard BE (2001) Brain cytokines and the psychopathology of depression. In: Leonard BE (ed) Antidepressants. Birkhauser Verlag, Basel, pp 109–120

    Chapter  Google Scholar 

  20. Leonard BE, Myint AM (2006) Inflammation and depression: is there a causal connection with dementia? Neurotox Res 10:149–160

    Article  CAS  PubMed  Google Scholar 

  21. Murray CJ, Lopez AD (1997) Global mortality, disability and the contribution of risk factors: global burden of disease study. Lancet 349(9063):1436–1442

    Article  CAS  PubMed  Google Scholar 

  22. Centers for Disease Control and Prevention (CDC) (2010) Current depression among adults—United States, 2006 and 2008. Morb Mortal Wkly Rep 59:1229–1235

    Google Scholar 

  23. Demyttenaere K, Bruffaerts R, Posada-Villa J et al (2004) Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization world mental health surveys. JAMA 291:2581–2590

    Article  PubMed  Google Scholar 

  24. Rozanski A, Blumenthal JA, Kaplan J (1999) Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation 99:2192–2217

    Article  CAS  PubMed  Google Scholar 

  25. Pratt LA, Brody DJ (2014) Depression in the U.S. household population, 2009–2012 (NCHS data brief, no 172). National Center for Health Statistics, Hyattsville, MD

    Google Scholar 

  26. Kovasic JC, Fuster V (2011) From treating complex coronary disease to promoting cardiovascular health: therapeutic transitions and challenges 2010-2020. Clin Pharmacol Ther 90(4):509–518

    Article  CAS  Google Scholar 

  27. Viles-Gonzalez JF, Fuster V, Badimon JJ (2004) Atherothrombosis: a widespread disease with unpredictable and life-threatening consequences. Eur Heart J 25:1197–1207

    Article  CAS  PubMed  Google Scholar 

  28. Terzic A, Waldman SA (2011) Chronic diseases: the emerging pandemic. Clin Transl Sci 4:225–226

    Article  PubMed  Google Scholar 

  29. CDC, NCHS (2015) Underlying cause of death 1999-2013 on CDC WONDER Online Database, released 2015. Data are from the Multiple Cause of Death Files, 1999-2013, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Accessed 3 Feb 2015

    Google Scholar 

  30. Mozaffarian D, Benjamin EJ, Go AS et al (2015) Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation 131:e29–e322

    Article  PubMed  Google Scholar 

  31. Barth J, Schumacher M, Herrmann-Lingen C (2004) Depression as a risk factor for mortality in patients with coronary heart disease: a meta-analysis. Psychosom Med 66:802–813

    Article  PubMed  Google Scholar 

  32. Gump BB, Matthews KA, Eberly LE, Chang YF (2005) MRFIT Research Group. Depressive symptoms and mortality in men: results from multiple risk factor intervention trial. Stroke 36:98–102

    Article  PubMed  Google Scholar 

  33. Ariyo AA, Haan M, Tangen CM et al (2000) Depressive symptoms and risks of coronary heart disease and mortality in elderly Americans. Cardiovascular Health Study Collaborative Research Group. Circulation 102:1773–1779

    Article  CAS  PubMed  Google Scholar 

  34. Ford DE, Mead LA, Chang PP (1998) Depression is a risk factor for coronary artery disease in men: the precursors study. Arch Intern Med 158(13):1422–1426

    Article  CAS  PubMed  Google Scholar 

  35. Penninx BW, Beekman AT, Honig A et al (2001) Depression and cardiac mortality: results from a community-based longitudinal study. Arch Gen Psychiatry 58:221–227

    Article  CAS  PubMed  Google Scholar 

  36. Jiang W, Alexander J, Christopher E et al (2001) Relationship of depression to increased risk of mortality and rehospitalization in patients with congestive heart failure. Arch Intern Med 161:1849–1856

    Article  CAS  PubMed  Google Scholar 

  37. Lesperance J, Frasure-Smith N, Talajic M, Bourassa M (2002) Five-year risk of cardiac mortality in relation to initial severity and one-year changes in depression symptoms in myocardial infarction. Circulation 105:1049–1053

    Article  PubMed  Google Scholar 

  38. Junger J, Schellberg D, Muller-Tasch T (2005) Depression increasingly predicts mortality in the course of congestive heart failure. Eur J Heart Fail 7:261–267

    Article  PubMed  Google Scholar 

  39. Sherwood A, Blumenthal JA, Trivedi R et al (2007) Relationship of depression to death or hospitalization in patients with heart failure. Arch Intern Med 167:367–373

    Article  PubMed  Google Scholar 

  40. Carney RM, Jaffe AS (2002) Treatment of depression following acute myocardial infarction. JAMA 288:750–751

    Article  PubMed  Google Scholar 

  41. Musselman DL, Evans DL, Nemeroff CB (1998) The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 55:580–592

    Article  CAS  PubMed  Google Scholar 

  42. O’Connor CM, Gurbel PA, Serebruany VL (2000) Depression in ischemic heart disease. Am Heart J 140:63–69

    Article  PubMed  Google Scholar 

  43. Wulsin LR, Evans JC, Vasan RS et al (2005) Depressive symptoms, coronary heart disease, and overall mortality in the Framingham heart study. Psychosom Med 67:697–702

    Article  PubMed  Google Scholar 

  44. Eaton WW, Fogel J, Armenian HK (2006) The consequences of psychopathology in the Baltimore Epidemiologic Catchment Area Follow-up. Medical and psychiatric co-morbidity over the lifespan. American Psychiatric Publishing, Washington, DC, p 21–38

    Google Scholar 

  45. Nicholson A, Kuper H, Hemingway H (2006) 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 27:2763–2774

    Article  PubMed  Google Scholar 

  46. McCaffery JM, Frasure-Smith N, Dube MP et al (2006) Common genetic vulnerability to depressive symptoms and coronary artery disease: a review and development of candidate genes related to inflammation and serotonin. Psychosom Med 68(2):187–200

    Article  CAS  PubMed  Google Scholar 

  47. Fielding R (1991) Depression and acute myocardial infarction: a review and reinterpretation. Soc Sci Med 32:1017–1027

    Article  CAS  PubMed  Google Scholar 

  48. Rudisch B, Nemeroff CB (2003) Epidemiology of comorbid coronary artery disease and depression. Biol Psychiatry 54:227–240

    Article  PubMed  Google Scholar 

  49. Schleifer SJ, Macari-Hinson MM, Coyle DA (1989) The nature and course of depression following myocardial infarction. Arch Intern Med 149:1785–1789

    Article  CAS  PubMed  Google Scholar 

  50. Frasure-Smith N, Lesperance F, Talajic M (1993) Depression following myocardial infarction: impact of 6-month survival. JAMA 270:1819–1825

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  53. Bush DE, Ziegelstein RC, Tayback M et al (2001) Even minimal symptoms of depression increase mortality risk after acute myocardial infection. Am J Cardiol 88:337–341

    Article  CAS  PubMed  Google Scholar 

  54. Selye H (1956) The stress of life. McGraw-Hill, New York

    Google Scholar 

  55. Tracey K (2007) Physiology and immunology of the cholinergic anti-inflammatory pathway. J Clin Invest 117(2):289–296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Thayer JF, Lane RD (2007) The role of vagal function in the risk for cardiovascular disease and mortality. Biol Psychol 74:224–242

    Article  PubMed  Google Scholar 

  57. Pavlov V, Tracey K (2005) The cholinergic anti-inflammatory pathway. Brain Behav Immun 19:493–499

    Article  CAS  PubMed  Google Scholar 

  58. Pavlov VA, Parrish WR, Rosas-Ballina M et al (2009) Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway. Brain Behav Immun 23(1):41–45. doi:10.1016/j.bbi.2008.06.011

    Article  CAS  PubMed  Google Scholar 

  59. Pavlov VA, Tracey KJ (2015) Neural circuitry and immunity. Immunol Res 63(1-3):38–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Otte C, Neylan TC, Pipkin SS et al (2005) Depressive symptoms and 24-hour urinary norepinephrine excretion levels in patients with coronary disease: findings from the heart and soul study. Am J Psychiatry 162(11):2139–2145

    Article  PubMed  PubMed Central  Google Scholar 

  61. Kemp AH, Quintana DS, Gray MA et al (2010) Impact of depression and antidepressant treatment on heart rate variability: a review and meta-analysis. Biol Psychiatry 67(11):1067–1074. doi:10.1016/j.biopsych.2009.12.012, Epub 6 Feb 2010

    Article  CAS  PubMed  Google Scholar 

  62. Licht CM, de Geus EJC, Zitman FG et al (2008) Association between major depressive disorder and heart rate variability in the Netherlands study of depression and anxiety (NESDA). Arch Gen Psychiatry 65(12):1358–1367

    Article  PubMed  Google Scholar 

  63. Porges SW (2001) The polyvagal theory: phylogenetic substrates of a social nervous system. Int J Psychophysiol 42(2):123–146

    Article  CAS  PubMed  Google Scholar 

  64. Porges SW (1995) Cardiac vagal tone; a physiological index of stress. Neurosci Biobehav Rev 19(2):225–233

    Article  CAS  PubMed  Google Scholar 

  65. Porges SW (1997) Emotion: an evolutionary by-product of the neural regulation of the autonomic nervous system. Ann N Y Acad Sci 807:62–77

    Article  CAS  PubMed  Google Scholar 

  66. Licht CM, Penninx BW, de Geus EJ (2011) To include or not to include? A response to the meta-analysis of heart rate variability and depression. Biol Psychiatry 69(4):e1; author reply e3–4. doi:10.1016/j.biopsych.2010.06.034

  67. Myint AM (2012) Kynurenines: from the perspective of major psychiatric disorders. FEBS J 279:1375–1385

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  69. Ur E, Pd W, Grossman A (1992) Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome. Eur Arch Psychiatry Clin Neurosci 241(5):317–322

    Article  CAS  PubMed  Google Scholar 

  70. Lett HS, Blumenthal JA, Babyak MA et al (2004) Depression as a risk factor for coronary artery disease: evidence, mechanisms, and treatment. Psychosom Med 66:305–315

    PubMed  Google Scholar 

  71. Maes M (1994) Cytokines in major depression. Biol Psychiatry 36:498–499

    Article  CAS  PubMed  Google Scholar 

  72. Anisman H, Ravindran AV, Griffiths J et al (1999) Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical features. Mol Psychiatry 4:182–188

    Article  CAS  PubMed  Google Scholar 

  73. Kaestner F, Hettich M, Peters M et al (2005) Different activation patterns of proinflammatory cytokines in melancholic and non-melancholic major depression are associated with HPA axis activity. J Affect Disord 87:305–311

    Article  CAS  PubMed  Google Scholar 

  74. Kim YK, Suh IB, Kim H et al (2002) The plasma levels of interleukin-12 in schizophrenia, major depression, and bipolar mania: effects of psychotropic drugs. Mol Psychiatry 7:1107–1114

    Article  CAS  PubMed  Google Scholar 

  75. Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H (2000) Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22:370–379

    Article  CAS  PubMed  Google Scholar 

  76. Mikova O, Yakimova R, Bosmans E et al (2001) Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis. Eur Neuropsychopharmacol 11:203–208

    Article  CAS  PubMed  Google Scholar 

  77. Myint AM, Leonard BE, Steinbusch HW, Kim YK (2005) Th1, Th2, and Th3 cytokine alterations in major depression. J Affect Disord 88:167–173

    Article  CAS  PubMed  Google Scholar 

  78. Piletz JE, Halaris A, Iqbal O et al (2009) Pro-inflammatory biomarkers in depression: treatment with venlafaxine. World J Biol Psychiatry 10:313–323

    Article  PubMed  Google Scholar 

  79. Schiepers OJ, Wichers MC, Maes M (2005) Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry 29:201–217

    Article  CAS  PubMed  Google Scholar 

  80. Thomas AJ, Davis S, Morris C et al (2005) Increase in interleukin-1beta in late-life depression. Am J Psychiatry 162:175–177

    Article  PubMed  Google Scholar 

  81. Boorman E, Romano GF, Russell A et al (2015) Are mood and anxiety disorders inflammatory diseases? Psychiatr Ann 45(5):240–248

    Article  Google Scholar 

  82. Dantzer R (2001) Cytokine-induced sickness behavior: mechanisms and implications. Ann N Y Acad Sci 933:222–234

    Article  CAS  PubMed  Google Scholar 

  83. Vollmer-Conna U, Fazou C, Cameron B et al (2004) Production of pro-inflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans. Psychol Med 34:1289–1297

    Article  CAS  PubMed  Google Scholar 

  84. von Känel R, Hepp U, Kraemer B et al (2006) Evidence for low-grade systemic proinflammatory activity in patients with posttraumatic stress disorder. J Psychiatr Res 41:744–752

    Article  Google Scholar 

  85. Dowlati Y, Herrmann N, Swardfager W et al (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67:446–457

    Article  CAS  PubMed  Google Scholar 

  86. Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65(9):732–741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Miller AH, Raison CL (2016) The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol 16:23–34

    Google Scholar 

  88. Di Iorio A, Ferrucci L, Sparvieri E et al (2003) Serum IL-1beta levels in health and disease: a population-based study. ‘The InCHIANTI study’. Cytokine 22:198–205

    Article  PubMed  CAS  Google Scholar 

  89. Biasucci LM (2004) 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 110:e560–e567

    Article  PubMed  Google Scholar 

  90. Empana JP, Sykes DH, Luc G et al (2005) 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 111:2299–2305

    Article  CAS  PubMed  Google Scholar 

  91. Anda R, Williamson D, Jones D et al (1993) Depressed affect, hopelessness, and the risk of ischemic heart disease in a cohort of U.S. adults. Epidemiology 4:285–294

    Article  CAS  PubMed  Google Scholar 

  92. Kamphuis MH, Kalmijn S, Tijhuis MA et al (2006) 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 13:199–206

    Article  PubMed  Google Scholar 

  93. Pratt LA, Ford DE, Crum RM et al (1996) Depression, psychotropic medication, and risk of myocardial infarction. Prospective data from the Baltimore ECA follow-up. Circulation 94:3123–3129

    Article  CAS  PubMed  Google Scholar 

  94. Müller N, Schwarz MJ, Dehning S et al (2006) 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 11(7):680–684

    Article  PubMed  CAS  Google Scholar 

  95. Akhondzadeh S, Jafari S, Raisi F et al (2009) Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depress Anxiety 26(7):607–611

    Article  CAS  PubMed  Google Scholar 

  96. Nery FG, Monkul ES, Hatch JP et al (2008) Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study. Hum Psychopharmacol 23(2):87–94

    Article  CAS  PubMed  Google Scholar 

  97. Halaris A, Alvi N, Meresh E, Sharma A (2014) Inflammation control reverses treatment-resistance in bipolar depression. Neurol Psychiatry Brain Res 20:12–13

    Article  Google Scholar 

  98. Himmerich H, Binder EB, Künzel HE et al (2006) Successful antidepressant therapy restores the disturbed interplay between TNF-alpha system and HPA axis. Biol Psychiatry 60:882–888

    Article  CAS  PubMed  Google Scholar 

  99. Kenis G, Maes M (2002) Effects of antidepressants on the production of cytokines. Int J Neuropsychopharmacol 5:401–412

    Article  CAS  PubMed  Google Scholar 

  100. Kubera M, Lin AH, Kenis G et al (2001) Anti-inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. J Clin Psychopharmacol 21:199–206

    Article  CAS  PubMed  Google Scholar 

  101. Kubera M, Kenis G, Bosmans E et al (2004) Stimulatory effect of antidepressants on the production of IL-6. Int Immunopharmacol 4:185–192

    Article  CAS  PubMed  Google Scholar 

  102. Mayer B, Holmer SR, Hengstenberg C et al (2005) Functional improvement in heart failure patients treated with beta-blockers is associated with a decline of cytokine levels. Int J Cardiol 103:182–186

    Article  PubMed  Google Scholar 

  103. Janssen DG, Caniato RN, Verster JC, Baune BT (2010) A psychoneuroimmunological review on cytokines involved in antidepressant treatment response. Human Psychopharmacol 25:201–215

    Article  CAS  Google Scholar 

  104. Halaris A (2015) Do antidepressants exert effects on the immune system? In: Mueller N, Myint A-M, Schwarz MJ (eds) Immunology and psychiatry, current topics in neurotoxicity. Springer, Berlin, pp 339–350. doi:10.1007/978-3-319-13602-8_16

    Google Scholar 

  105. Ross R (1999) Atherosclerosis-an inflammatory disease. N Engl J Med 340:115–126

    Article  CAS  PubMed  Google Scholar 

  106. Lind L (2003) Circulating markers of inflammation and atherosclerosis. Atherosclerosis 169:203–214

    Article  CAS  PubMed  Google Scholar 

  107. Frasure-Smith N, Lespérance F, Irwin MR et al (2007) Depression, C-reactive protein and two-year major adverse cardiac events in men after acute coronary syndromes. Biol Psychiatry 62(4):302–308

    Article  CAS  PubMed  Google Scholar 

  108. Hansson G (2005) Inflammation, atherosclerosis and coronary artery disease. N Engl J Med 352(16):1685–1695

    Article  CAS  PubMed  Google Scholar 

  109. Seta Y, Shan K, Bozkurt B et al (1996) Basic mechanisms in heart failure: the cytokine hypothesis. J Card Fail 2:243–249

    Article  CAS  PubMed  Google Scholar 

  110. Petersen JW, Felker M (2006) Inflammatory biomarkers in heart failure. Congest Heart Fail 12:324–328

    Article  CAS  PubMed  Google Scholar 

  111. Casas JP, Shah T, Hingorani AD et al (2008) C-reactive protein and coronary heart disease: a critical review. J Intern Med 264:295–314

    Article  CAS  PubMed  Google Scholar 

  112. Koenig W (2013) High-sensitivity C-reactive protein and atherosclerotic disease: from improved risk prediction to risk-guided therapy. Int J Cardiol 168:5126–5134

    Article  PubMed  Google Scholar 

  113. Tsimikas S, Willerson JT, Ridker PM (2006) C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol 47:C19–C31

    Article  CAS  PubMed  Google Scholar 

  114. Hamer M, Batty GD, Marmot MG et al (2011) Anti-depressant medication use and C-reactive protein: results from two population-based studies. Brain Behav Immun 25(1):168–173

    Article  CAS  PubMed  Google Scholar 

  115. Wium-Andersen MK, Ørsted DD, Nielsen SF et al (2013) Elevated C-reactive protein levels, psychological distress, and depression in 73 131 Individuals. JAMA Psychiatry 70(2):176–184

    Article  CAS  PubMed  Google Scholar 

  116. Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C-reactive protein, IL-a, and IL-6: a meta-analysis. Psychosom Med 71:171–186

    Article  CAS  PubMed  Google Scholar 

  117. Copeland WE, Shanahan L, Worthman C et al (2012) Cumulative depression episodes predict later C-reactive protein levels: a prospective analysis. Biol Psychiatry 71(1):15–21

    Article  CAS  PubMed  Google Scholar 

  118. Frank MG, Baratta MV, Sprunger DB et al (2007) Microglia serve as a neuroimmune substrate for stress-induced potentiation of CNS pro-inflammatory cytokine responses. Brain Behav Immun 21:47–59

    Article  CAS  PubMed  Google Scholar 

  119. Raison CL, Miller AH (2013) Do cytokines really sing the blues? Cerebrum: The Dana Foundation, p 1–16. http://dana.org/Cerebrum/2013/Do_Cytokines_Really_Sing_the_Blues_/#sthash.GLt3Sf7k.dpuf

  120. Wu Y, Potempa LA, El Kebir D, Filep JG (2015) C-reactive protein and inflammation: conformational changes affect function. Biol Chem 396(11):1181–1197

    Article  CAS  PubMed  Google Scholar 

  121. Bonetti PO, Lerman LO, Lerman A (2003) Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 23:168–175

    Article  CAS  PubMed  Google Scholar 

  122. Cleland SJ, Sattar N, Petrie JR et al (2000) Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. Clin Sci 98:531–535

    Article  CAS  PubMed  Google Scholar 

  123. Musselman DL, Tomer A, Manatunga AK et al (1996) Exaggerated platelet reactivity in major depression. Am J Psychiatry 153:1313–1317

    Article  CAS  PubMed  Google Scholar 

  124. Musselman DL, Marzec UM, Manatunga A et al (2000) Platelet reactivity in depressed patients treated with paroxetine: preliminary findings. Arch Gen Psychiatry 57:875–882

    Article  CAS  PubMed  Google Scholar 

  125. Nemeroff CB, Musselman DL (2000) Are platelets the link between depression and ischemic heart disease? Am Heart J 140(Suppl 4):57–62

    Article  CAS  PubMed  Google Scholar 

  126. Piletz JE, Zhu H, Madakasira S et al (2000) Elevated P-selectin on platelets in depression: response to bupropion. J Psychiatry Res 34:397–404

    Article  CAS  Google Scholar 

  127. Tucci M, Quatraro C, Frassanito MA, Silvestris F (2006) Deregulated expression of monocyte chemoattractant protein-1 (MCP-1) in arterial hypertension: role in endothelial inflammation and atheromasia. J Hypertens 24:1307–1318

    Article  CAS  PubMed  Google Scholar 

  128. Verma S, Buchanan MR, Anderson TJ (2003) Endothelial function testing as a biomarker of vascular disease. Circulation 108:2054–2059

    Article  PubMed  Google Scholar 

  129. Broadley AJ, Korszun A, Jones CJ, Frenneaux MP (2002) Arterial endothelial function is impaired in treated depression. Heart 88:521–523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Rybakowski JK, Wykretowicz A, Heymann-Szlachcinska A, Wysocki H (2006) Impairment of endothelial function in unipolar and bipolar depression. Biol Psychiatry 60(8):889–891

    Article  CAS  PubMed  Google Scholar 

  131. Do DP, Dowd JB, Ranjit N et al (2010) Hopelessness, depression, and early markers of endothelial dysfunction in U.S. adults. Psychosom Med 72:613–619

    Article  PubMed  PubMed Central  Google Scholar 

  132. Myint AM, Kim YK (2003) Cytokine-serotonin interaction through IDO; a neurodegeneration hypothesis of depression. Med Hypotheses 61(5–6):519–525

    Article  CAS  PubMed  Google Scholar 

  133. Myint AM, Kim YK, Verkerk R et al (2007) Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord 89(1):143–151

    Article  CAS  Google Scholar 

  134. Raison CL, Dantzer R, Kelley KW et al (2010) CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-a: relationship to CNS immune responses and depression. Mol Psychiatry 15:393–403

    Article  CAS  PubMed  Google Scholar 

  135. Halaris A, Myint AM, Savant V et al (2015) Does escitalopram reduce neurotoxicity in major depression? J Psychiatr Res 66–67:118–126

    Article  PubMed  Google Scholar 

  136. Zhu C-B, Lindler KM, Owens AW et al (2010) Interleukin-1 receptor activation by systemic lipopolysaccharide induces behavioral despair linked to MAPK regulation of CNS serotonin transporters. Neuropsychopharmacology 35:2510–2520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Baganz NL, Lindler KM, Zhu CB et al (2015) A requirement of serotonergic p38α mitogen-activated protein kinase for peripheral immune system activation of CNS serotonin uptake and serotonin-linked behaviors. Transl Psychiatry 5, e671. doi:10.1038/tp.2015.168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Hsu JW, Lirng JF, Wang SJ et al (2014) Association of thalamic serotonin transporter and interleukin-10 in bipolar I disorder: a SPECT study. Bipolar Disord 16(3):241–248. doi:10.1111/bdi.12164, Epub 20 Dec 2013

    Article  CAS  PubMed  Google Scholar 

  139. Amsterdam JD, Newberg AB, Newman CF et al (2013) Change over time in brain serotonin transporter binding in major depression: effects of therapy measured with [123I]-ADAM SPECT. J Neuroimaging 23(4):469–476. doi:10.1111/jon.12035

    Article  PubMed  PubMed Central  Google Scholar 

  140. aan het Rot M, Collins KA, Murrough JW et al (2010) Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry 67:139–145

    Google Scholar 

  141. Berman RM, Cappiello A, Anand A et al (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47:351–354

    Article  CAS  PubMed  Google Scholar 

  142. Duman RS, Li N, Liu RJ et al (2012) Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology 62:35–41

    Article  CAS  PubMed  Google Scholar 

  143. Schwarcz R (2004) The kynurenine pathway of tryptophan degradation as a drug target. Curr Opin Pharmacol 4:12–17

    Article  CAS  PubMed  Google Scholar 

  144. Tavares RG, Tasca CI, Santos CE et al (2002) Quinolinic acid stimulates synaptosomal glutamate release and inhibits glutamate uptake into astrocytes. Neurochem Int 40:621–627

    Article  CAS  PubMed  Google Scholar 

  145. Savitz J, Drevets WC, Smith CM et al (2015) Putative neuroprotective and neurotoxic kynurenine pathway metabolites are associated with hippocampal and amygdalar volumes in subjects with major depressive disorder. Neuropsychopharmacology 40:463–471

    Article  CAS  PubMed  Google Scholar 

  146. Erhardt S, Lim CK, Linderholm KR et al (2013) Connecting inflammation with glutamate agonism in suicidality. Neuropsychopharmacology 38:743–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Dantzer R, Walker A (2014) Is there a role for glutamate-mediated excitotoxicity in inflammation-induced depression? J Neural Transm (Vienna) 121:925–932

    Article  CAS  Google Scholar 

  148. Malarkey E, Parpura V (2008) Mechanisms of glutamate release from astrocytes. Neurochem Int 52:142–154

    Article  CAS  PubMed  Google Scholar 

  149. Hardingham GE, Bading H (2010) Synaptic versus extrasynaptic NMDA receptor signaling: implications for neurodegenerative disorders. Nat Rev Neurosci 11:682–696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Miller AH (2013) Conceptual confluence: the kynurenine pathway as a common target for ketamine and the convergence of the inflammation and glutamate hypotheses of depression. Neuropsychopharmacology 38:1607–1608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Haroon E, Woolwine BJ, Chen X et al (2014) IFN-alpha induced cortical and subcortical glutamate changes assessed by magnetic resonance spectroscopy. Neuropsychopharmacology 39:1777–1785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Haroon E, Felger JC, Woolwine BJ et al (2015) Age-related increases in basal ganglia glutamate are associated with TNF, reduced motivation and decreased psychomotor speed during IFN-alpha treatment: preliminary findings. Brain Behav Immun 46:17–22

    Article  CAS  PubMed  Google Scholar 

  153. Haroon E, Fleischer CC, Felger JC et al (2016) Conceptual convergence: increased inflammation is associated with increased basal ganglia glutamate in patients with major depression. Molecular Psychiatry advance online publication, 12 Jan 2016. doi:10.1038/mp.2015.206

  154. Haase J, Brown E (2015) Integrating the monoamine, neurotrophin and cytokine hypotheses of depression—a central role for the serotonin transporter? Pharmacol Ther 147:1–11. doi:10.1016/j.pharmthera.2014.10.002, Epub 1 Nov 2014. Review

    Article  CAS  PubMed  Google Scholar 

  155. Glassman AH, Bigger TJ Jr, Gaffney M (2009) Psychiatric characteristics associated with long-term mortality among 361 patients having an acute coronary syndrome and major depression. Arch Gen Psychiatry 66(9):1022–1029

    Article  PubMed  Google Scholar 

  156. Halaris A (2013) Psychocardiology: moving toward a new subspecialty. Future Cardiol 9(5):635–640

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Neuroscience, Stritch School of Medicine, Loyola University Chicago and Loyola University Medical Center, 2160 South First Avenue, Maywood, IL, 60153, USA

    Angelos Halaris

Authors
  1. Angelos Halaris
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Angelos Halaris .

Editor information

Editors and Affiliations

  1. Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Robert Dantzer

  2. Nutrition and Integrative Neurobiology, INRA, University of Bordeaux, Bordeaux, France

    Lucile Capuron

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Halaris, A. (2016). Inflammation-Associated Co-morbidity Between Depression and Cardiovascular Disease. In: Dantzer, R., Capuron, L. (eds) Inflammation-Associated Depression: Evidence, Mechanisms and Implications. Current Topics in Behavioral Neurosciences, vol 31. Springer, Cham. https://doi.org/10.1007/7854_2016_28

Download citation

Publish with us

Policies and ethics

Search

Navigation