Advertisement

The inflammatory response system activation model of major depression

Part of the Key Topics in Brain Research book series (KEYTOPICS)

Summary

The present paper proposes a concise inflammatory response system (IRS)- activation model of major depression. The evidence that alterations in the 1RS participate in the pathophysiology or even etiology of major depression consists of the following. 1) Confirmed findings of in vivo 1RS activation in major depression, such as increased numbers of leukocytes, monocytes, neutrophils, activated T-lymphocytes, increased secretion of neopterin and prostaglandins, and increased secretion of proinflammatory cytokines, such as interleukin-lβ (IL-lβ), IL-6 and interferon-γ (IFNγ). 2) A variety of antidepressants, such as selective serotonin reuptake inhibitors and tricyclic antidepressants, have negative immunoregulatory activities. 3) Activation of the 1RS in major depression is significantly related to some of the neuroendocrine disorders in that illness. 4) Proinflammatory cytokines, such as IL-1, IL-6 and interferons given to humans or animals can produce depressive symptoms or full blown major depression. 5) The 1RS activation model may account for the multicausal etiology of major depression whereby external or psychosocial Stressors (negative life events), and internal or organic Stressors are considered to play a pivotal role in the etiology of depression.

Keywords

Proinflammatory Cytokine Major Depression Acute Phase Protein Psychomotor Retardation Chronic Mild Stress 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Jefferson JW, Greist JH (1994) Mood disorders. In: Hales RE, Yudofsky SC, Talbott JA (eds) Textbook of psychiatry. The American Psychiatric Press, Washington, pp 470–476Google Scholar
  2. 2.
    Herbert TB, Cohen S (1993) Depression and immunity: a meta-analytic review. Psychol Bull 113: 472–486PubMedCrossRefGoogle Scholar
  3. 3.
    Maes M, Lambrechts J, Bosmans E, Jacobs J, Suy E, Vandervorst C, Dejonckheere C, Minner B, Raus J (1992) Evidence for a systemic immune activation during depression: results of leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining. Psychol Med 22: 45–53PubMedCrossRefGoogle Scholar
  4. 4.
    Muller N, Ackenheil M, Hofschuster E (1989) Altered T-cell number and reduced suppressor cell activity in patients with affective psychosis. In: Hadden JW, Masek K, Nistico G (eds) Interactions among central nervous system. Neuroendocrine and immune systems. Pythagora Press, Rome, pp 385–394Google Scholar
  5. 5.
    Sluzewska A, Rybakowski JK, Sobieska M, Bosmans E, Pollet H, Wiktorowicz K (1996) Increased levels of alpha-1-acid glycoprotein and interleukin-6 in refractory depression. DepressionGoogle Scholar
  6. 6.
    Sluzewska A, Rybakowski J, Bosmans E, Sobieska M, Berghmans R, Maes M, Wiktorowicz K (1996) Indicators of immune activation in major depression. Psychiatr Res 64: 161–167CrossRefGoogle Scholar
  7. 7.
    Seidel A, Arolt V, Hunstiger M, Rink L, Behnisch A, Kirchner H (1996) Major depressive disorder is associated with elevated monocyte counts. Acta Psychiatr Scand 94: 198–204PubMedCrossRefGoogle Scholar
  8. 8.
    Maes M, Stevens W, Declerck L, Bridts C, Peeters D, Schotte C, Cosyns P (1993) A significantly increased expression of T cell activation markers in depression: additional evidence for an inflammatory process during that illness. Prog Psychopharmacolol Biol Psychiatry 17: 214–255Google Scholar
  9. 9.
    Perini GI, Zara M, Carraro C, Tosin C, Gava F, Santucci MG, Valverde S, Defranchis G (1995) Psychoimmunoendocrine effects of panic disorder. Hum Psychopharmacol 10: 461–465CrossRefGoogle Scholar
  10. 10.
    Duch DS, Woolf JH, Nichol CA, Davidson JR, Garbutt JC (1984) Urinary excretion of biopterin and neopterin in psychiatric disorders. Psychiatr Res 11: 83–89CrossRefGoogle Scholar
  11. 11.
    Dunbar PR, Hill J, Neale TJ, Mellsop GW (1992) Neopterin measurement provides evidence of altered cell-mediated immunity in patients with depression, but not with schizophrenia. Psychol Med 22: 1051–1057PubMedCrossRefGoogle Scholar
  12. 12.
    Maes M, Scharpé S, Meltzer HY, Okayli G, Bosmans E, D’Hondt P, Vanden Bossche B, Cosyns P (1994) Increased neopterin and interferon y secretion and lower availability of L-tryptophan in major depression: further evidence for activation of cell-mediated immunity. Psychiatr Res 54: 143–160CrossRefGoogle Scholar
  13. 13.
    Bonaccorso S, Lin A, Verkerk R, VanHunsel F, Libbrecht I, Scharpé S, DeClerck L, Stevens W, Biondi M, Janca A, Maes M (1998) Immune markers in fibromyalgia: comparison with major depressed patients and normal volunteers. J Affect Disord 48: 75–82PubMedCrossRefGoogle Scholar
  14. 14.
    Linnoila M, Whorton R, Rubinow DR, Cowdry RW, Ninan PT, Waters RN (1983) CSF prostaglandin levels in depressed and schizophrenic patients. Arch Gen Psychiatry 40: 405–406PubMedCrossRefGoogle Scholar
  15. 15.
    Calabrese JR, Skwerer RG, Barna B, Gulledge AD, Valenzuela R, Butkus A, Subichin S, Krupp NE (1986) Depression, immunocompetence, and prostaglandins of the E series. Psychiatr Res 17: 41–47CrossRefGoogle Scholar
  16. 16.
    Song C, Lin A, Bonaccorso S, Heide C, Verkerk R, Kenis G, Bosmans E, Scharpe S, Cosyns P, Dejong R, Maes M (1998) The inflammatory response system and the availability of tryptophan to the brain of patients with major depression and sleep disorders. J Affect Disord 49: 211–219PubMedCrossRefGoogle Scholar
  17. 17.
    Maes M, Meltzer HY, Bosmans E, Bergmans R, Vandoolaeghe E, Ranjan R, Desnyder R (1995) Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord 34: 301–309PubMedCrossRefGoogle Scholar
  18. 18.
    Seidel A, Arolt V, Hunstiger M, et al. (1995) Cytokine production and serum proteins in depression. Scand J Immunol 41: 534–538PubMedCrossRefGoogle Scholar
  19. 19.
    Seidel A, Arolt V, Hunstiger M, Rink L, Behnisch A, Kirchner H (1996) Increased CD56+ natural killer cells and related cytokines in major depression. Clin Immunol Immunopathol 78: 83–85PubMedCrossRefGoogle Scholar
  20. 20.
    Maes M, Wauters A, Verkerk R, Neels H, vanGastel A, Cosyns P, Scharpe S, Desnyder R (1996) Lower L-tryptophan availability in depression: a marker of a more generalized disorder in protein metabolism. Neuropsychopharmacol 15: 243–251CrossRefGoogle Scholar
  21. 21.
    Nassberger L, Traskman-Bendz L (1993) Increased soluble interleukin-2 receptor concentrations in suicide attempters. Acta Psychiatr Scand 88: 48–52PubMedCrossRefGoogle Scholar
  22. 22.
    Maes M (1993) Acute phase protein alterations in major depression: a review. Rev Neurosci 4: 407–416PubMedGoogle Scholar
  23. 23.
    Joyce PR, Hawes CR, Mulder RT, Sellman JD, Wilson DA, Boswell DR (1992) Elevated levels of acute phase plasma proteins in major depression. Biol Psychiatry 32: 1035–1041PubMedCrossRefGoogle Scholar
  24. 24.
    Song C, Dinan T, Leonard BE (1994) Changes in immunoglobulin, complement and acute phase protein levels in the depressed patients and normal controls. J Affect Disord 30: 283–288PubMedCrossRefGoogle Scholar
  25. 25.
    Sluzewska A, Rybakowski JK, Sobieska M, Wiktorowicz K (1996) Concentrations and microheterogeneity glycophorms of alpha-1-acid gly-coprotein in major depression. J Affect Disord 39: 149–155PubMedCrossRefGoogle Scholar
  26. 26.
    Sluzewska A, Nowakowska E, Gryska K, Mackiewicz A (1994) Haptoglobin levels in a chronic mild stress model of depression in rats before and after treatment. Eur Neuropharmacol P-l-18: 302CrossRefGoogle Scholar
  27. 27.
    Song C, Leonard BE (1994) An acute phase protein response in the olfactory bulbectomized rat: effect of sertraline treatment. Med Sci Res 22: 313–314Google Scholar
  28. 28.
    Sluzewska A, Rybakowski JK, Laciak M, Mackiewicz A, Sobieska M, Wiktorowiz K (1995) Interleukin-6 serum levels in depressed patients before and after treatment with fluoxetine. Ann NY Acad Sci 762: 474–476PubMedCrossRefGoogle Scholar
  29. 29.
    Maes M, Delange J, Ranjan R, Meltzer HY, Desnyder R, Cooremans W, Scharpé S (1997) Acute phase proteins in schizophrenia, mania and major depression: modulation by psychotropic drugs. Psychiatr Res 66: 1–11CrossRefGoogle Scholar
  30. 30.
    Xia II, DePierre JW, Nassberger L (1996) Tricyclic antidepressants inhibit IL-6, IL-lβ and TNF-α release in human blood monocytes and IL-2 and interferon-y in T cells. Immunopharmacol 34: 27–37CrossRefGoogle Scholar
  31. 31.
    Maes M, Bosmans E, Meltzer HY, Scharpé S, Suy E (1993) Interleukin-lß: a putative mediator of HPA-axis hyperactivity in major depression? Am J Psychiatry 150: 1189–1193PubMedGoogle Scholar
  32. 32.
    Pariante CM, Pearce BD, Pisell TL, et al. (1997) Steroid-independent modulation of the glucocorticoid receptor: relevance for psychiatry and immunology. In: Abstract Book WPA Symposium “Psychiatry in the Three Ages of Man”. WPA, Rome, pp 21Google Scholar
  33. 33.
    Kent S, Bluthé R-M, Kelley KW, Dantzer R (1992) Sickness behavior as a new target for drug development. TiPS 13: 24–28PubMedGoogle Scholar
  34. 34.
    Yirmiya R (1996) Endotoxin produces a depressive-like episode in rats. Brain Res 711: 163–174PubMedCrossRefGoogle Scholar
  35. 35.
    McDonald EM, Mann AH, Thomas HC (1987) Interferons as mediators of psychiatric morbidity. Lancet 2: 1175–1178PubMedCrossRefGoogle Scholar
  36. 36.
    Maes M, Meltzer HY, Scharpé S, Cooreman W, Uyttenbroeck W, Suy E, Vandervorst C, Raus J, Cosyns P (1993) Psychomotor retardation, anorexia, weight loss, sleep disturbances and loss of energy: psychopathological correlates of hyperhaptoglobinemia in major depression. Psychiatr Res 47: 229–241CrossRefGoogle Scholar
  37. 37.
    Maes M (1997) The immune pathophysiology of major depression. In: Honig A, van Praag HM (eds) Depression: neurobiological, psychopathological and therapeutic advances. John Wiley, London, pp 197–215Google Scholar
  38. 38.
    Yirmiya R (1997) Behavioral and psychological effects of immune activation: implications for depression due to a general medical condition. Curr Opin Psychiatry 10: 470–476CrossRefGoogle Scholar
  39. 39.
    LeMay LG, Vander AJ, Kluger MJ (1990) The effects of psychological stress on plasma interleukin-6 activity in rats. Physiol Beh 47: 957–961CrossRefGoogle Scholar
  40. 40.
    Zhou D, Kusnecov AW, Shurin MR, De Paoli M, Rabin B (1993) Exposure to physical and psychological Stressors elevates plasma interleukin-6: relationship to the activation of hypothalamic-pituitary-adrenal axis. Endocrinol 133: 2523–2530CrossRefGoogle Scholar
  41. 41.
    Soszynski D, Kozak W, Conn CA, Rudolph K, Kluger MJ (1996) Beta-adrenoceptor antagonists suppress elevation in body temperature and increase plasma IL-6 in rats exposed to open field. Neuroendocrinol 63: 459–467CrossRefGoogle Scholar
  42. 42.
    Minami M, Kuraishi Y, Yamaguchi T, Nakai S, Hirai Y, Satoh M (1990) Immobilization stress induces interleukin-1 beta mRNA in the rat hypothalamus. Neurosci Lett 25: 254–256Google Scholar
  43. 43.
    Maes M, Song C, Lin A, Gabriels L, DeJongh R, Van Gastel A, Kenis G, Bosmans E, DeMeester I, Benoyt I, Neels H, Demedts P, Janca A, Scharpe S, Smith RS (1998) The effects of psychological stress on humans: increased production of proinflammatory cytokines and a Th-1-like response in stress-induced anxiety. Cytokine 10: 313–318PubMedCrossRefGoogle Scholar
  44. 44.
    Maes M, Song C, Lin A, Dejong R, Kenis G, Bosmans E, DeMeester I, Neels H, Scharpe S (1998) Immune and clinical correlates of psychological stress-induced production of interferon-y and IL-10 in humans. In: Plotnikoff NP et al. (eds) Cytokines, stress, and immunity. CRC Press, Boca Raton, pp 39–50Google Scholar

Copyright information

© Springer-Verlag Wien 1999

Authors and Affiliations

  • M. Maes
    • 1
    • 2
  1. 1.Clinical Research Center for Mental Health, and University Department of PsychiatryAntwerpBelgium
  2. 2.Department of PsychiatryVanderbilt UniversityNashvilleUSA

Personalised recommendations