Skip to main content
SpringerLink
Log in

Psychoneuroimmunology in Pula: A Hot Topic with a Long Past

  • Chapter
  • First Online:
Mind, Brain and Education

  • 286 Accesses

Abstract

Psychoneuroimmunology and neuroimmunology have become important topics in psychiatric and neurologic research in the last 20 years, and the growing interest in these fields and the associated increasing scientific insights are well reflected in the programs of the Pula congresses. Scientific interest in psychoneuroimmunology has grown enormously in the past few years because the pathological mechanisms of psychiatric disorders remain unknown and because of groundbreaking findings on the interaction between the immune and central nervous systems. In Pula, the fruitful discussions between neurologists and psychiatrists reflect the benefit of these interdisciplinary meetings. Neuroimmunology has been advancing for many years, in particular in multiple sclerosis research, and psychoneuroimmunology has made great methodological progress more recently. Research has focused in particular on schizophrenia, major depression, and anxiety disorders. Meanwhile, a benefit of anti-inflammatory treatment in major depression and schizophrenia has been demonstrated in clinical studies and meta-analyses. Future studies are warranted to evaluate the exact immunological mechanisms in the pathophysiology of psychiatric disorders, optimize the anti-inflammatory treatment approach, and develop more targeted, personalized therapies. Accordingly, psychoneuroimmunology will continue to be an important topic at future Pula Mind and Brain meetings.

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 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 159.99
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

Similar content being viewed by others

References

  1. Ader R, Felten DL. Psychoneuroimmunology. San Diego, New York, Toronto: Academic; 1991.

    Google Scholar 

  2. Besedovsky H, del Rey A, Sorkin E, Da Prada M, Burri R, Honegger C. The immune response evokes changes in brain noradrenergic neurons. Science. 1983;221(4610):564–6.

    Article  CAS  Google Scholar 

  3. Maes M, Bosmans E, Suy E, Vandervorst C, De Jonckheere C, Raus J. Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology. 1990;24(3):115–20.

    Article  Google Scholar 

  4. Maes M, Lambrechts J, Bosmans E, Jacobs J, Suy E, Vandervorst C, et al. Evidence for a systemic immune activation during depression: results of leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining. Psychol Med. 1992;22(1):45–53.

    Article  CAS  Google Scholar 

  5. Muller N, Ackenheil M, Eckstein R, Hofschuster E, Mempel W. Reduced suppressor cell function in psychiatric patients. Ann N Y Acad Sci. 1987;496:686–90.

    Article  CAS  Google Scholar 

  6. Muller N, Ackenheil M, Hofschuster E, Mempel W, Eckstein R. Cellular immunity in schizophrenic patients before and during neuroleptic treatment. Psychiatry Res. 1991;37(2):147–60.

    Article  CAS  Google Scholar 

  7. Muller N, Hofschuster E, Ackenheil M, Mempel W, Eckstein R. Investigations of the cellular immunity during depression and the free interval: evidence for an immune activation in affective psychosis. Prog Neuro-Psychopharmacol Biol Psychiatry. 1993;17(5):713–30.

    Article  CAS  Google Scholar 

  8. Meyer U, Schwendener S, Feldon J, Yee BK. Prenatal and postnatal maternal contributions in the infection model of schizophrenia. Exp Brain Res. 2006;173(2):243–57. https://doi.org/10.1007/s00221-006-0419-5.

    Article  Google Scholar 

  9. Muller N, Ackenheil M. Immunoglobulin and albumin content of cerebrospinal fluid in schizophrenic patients: relationship to negative symptomatology. Schizophr Res. 1995;14(3):223–8. https://doi.org/10.1016/0920-9964(94)00045-a.

    Article  CAS  Google Scholar 

  10. Muller N, Riedel M, Hadjamu M, Schwarz MJ, Ackenheil M, Gruber R. Increase in expression of adhesion molecule receptors on T helper cells during antipsychotic treatment and relationship to blood-brain barrier permeability in schizophrenia. Am J Psychiatry. 1999;156(4):634–6.

    Article  CAS  Google Scholar 

  11. Dantzer R, Kelley KW. Stress and immunity: an integrated view of relationships between the brain and the immune system. Life Sci. 1989;44(26):1995–2008.

    Article  CAS  Google Scholar 

  12. 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. https://doi.org/10.1038/nrn2297.

    Article  CAS  PubMed Central  Google Scholar 

  13. Reichenberg A, Kraus T, Haack M, Schuld A, Pollmacher T, Yirmiya R. Endotoxin-induced changes in food consumption in healthy volunteers are associated with TNF-alpha and IL-6 secretion. Psychoneuroendocrinology. 2002;27(8):945–56.

    Article  CAS  Google Scholar 

  14. Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A, et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry. 2001;58(5):445–52.

    Article  CAS  Google Scholar 

  15. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27(1):24–31. https://doi.org/10.1016/j.it.2005.11.006.

    Article  CAS  Google Scholar 

  16. Danner M, Kasl SV, Abramson JL, Vaccarino V. Association between depression and elevated C-reactive protein. Psychosom Med. 2003;65(3):347–56.

    Article  CAS  Google Scholar 

  17. Hafner S, Baghai TC, Eser D, Schule C, Rupprecht R, Bondy B, et al. C-reactive protein is associated with polymorphisms of the angiotensin-converting enzyme gene in major depressed patients. J Psychiatr Res. 2008;42(2):163–5. https://doi.org/10.1016/j.jpsychires.2007.02.002.

    Article  Google Scholar 

  18. Ford DE, Erlinger TP. Depression and C-reactive protein in US adults: data from the third National Health and Nutrition Examination Survey. Arch Intern Med. 2004;164(9):1010–4. https://doi.org/10.1001/archinte.164.9.1010.

    Article  Google Scholar 

  19. Kling MA, Alesci S, Csako G, Costello R, Luckenbaugh DA, Bonne O, et al. Sustained low-grade pro-inflammatory state in unmedicated, remitted women with major depressive disorder as evidenced by elevated serum levels of the acute phase proteins C-reactive protein and serum amyloid A. Biol Psychiatry. 2007;62(4):309–13. https://doi.org/10.1016/j.biopsych.2006.09.033.

    Article  CAS  Google Scholar 

  20. Cizza G, Eskandari F, Coyle M, Krishnamurthy P, Wright EC, Mistry S, et al. Plasma CRP levels in premenopausal women with major depression: a 12-month controlled study. Horm Metab Res. 2009;41(8):641–8. https://doi.org/10.1055/s-0029-1220717.

    Article  CAS  PubMed Central  Google Scholar 

  21. Gimeno D, Marmot MG, Singh-Manoux A. Inflammatory markers and cognitive function in middle-aged adults: the Whitehall II study. Psychoneuroendocrinology. 2008;33(10):1322–34. https://doi.org/10.1016/j.psyneuen.2008.07.006.

    Article  CAS  PubMed Central  Google Scholar 

  22. Maes M, Meltzer HY, Bosmans E, Bergmans R, Vandoolaeghe E, Ranjan R, et al. Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord. 1995;34(4):301–9.

    Article  CAS  Google Scholar 

  23. Maes M, Meltzer HY, Buckley P, Bosmans E. Plasma-soluble interleukin-2 and transferrin receptor in schizophrenia and major depression. Eur Arch Psychiatry Clin Neurosci. 1995;244(6):325–9.

    Article  CAS  Google Scholar 

  24. Irwin M. Immune correlates of depression. Adv Exp Med Biol. 1999;461:1–24. https://doi.org/10.1007/978-0-585-37970-8_1.

    Article  CAS  Google Scholar 

  25. Nunes SO, Reiche EM, Morimoto HK, Matsuo T, Itano EN, Xavier EC, et al. Immune and hormonal activity in adults suffering from depression. Braz J Med Biol Res. 2002;35(5):581–7.

    Article  CAS  Google Scholar 

  26. Müller N, Schwarz MJ. Immunology in anxiety and depression. In: Kasper S, den Boer JA, Sitsen JMA, editors. Handbook of depression and anxiety. New York: Marcel Dekker; 2002. p. 267–88.

    Google Scholar 

  27. Mikova O, Yakimova R, Bosmans E, Kenis G, Maes M. Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis. Eur Neuropsychopharmacol. 2001;11(3):203–8.

    Article  CAS  Google Scholar 

  28. Herbert TB, Cohen S. Depression and immunity: a meta-analytic review. Psychol Bull. 1993;113(3):472–86.

    Article  CAS  Google Scholar 

  29. Seidel A, Arolt V, Hunstiger M, Rink L, Behnisch A, Kirchner H. Major depressive disorder is associated with elevated monocyte counts. Acta Psychiatr Scand. 1996;94(3):198–204.

    Article  CAS  Google Scholar 

  30. Rothermundt M, Arolt V, Fenker J, Gutbrodt H, Peters M, Kirchner H. Different immune patterns in melancholic and non-melancholic major depression. Eur Arch Psychiatry Clin Neurosci. 2001;251(2):90–7.

    Article  CAS  Google Scholar 

  31. Duch DS, Woolf JH, Nichol CA, Davidson JR, Garbutt JC. Urinary excretion of biopterin and neopterin in psychiatric disorders. Psychiatry Res. 1984;11(2):83–9.

    Article  CAS  Google Scholar 

  32. Dunbar PR, Hill J, Neale TJ, Mellsop GW. Neopterin measurement provides evidence of altered cell-mediated immunity in patients with depression, but not with schizophrenia. Psychol Med. 1992;22(4):1051–7.

    Article  CAS  Google Scholar 

  33. Maes M, Scharpe S, Meltzer HY, Okayli G, Bosmans E, D'Hondt P, et al. Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: further evidence for an immune response. Psychiatry Res. 1994;54(2):143–60.

    Article  CAS  Google Scholar 

  34. Bonaccorso S, Lin AH, Verkerk R, Van Hunsel F, Libbrecht I, Scharpe S, et al. Immune markers in fibromyalgia: comparison with major depressed patients and normal volunteers. J Affect Disord. 1998;48(1):75–82.

    Article  CAS  Google Scholar 

  35. Muller N, Myint AM, Schwarz MJ. Inflammatory biomarkers and depression. Neurotox Res. 2011;19(2):308–18. https://doi.org/10.1007/s12640-010-9210-2.

    Article  CAS  Google Scholar 

  36. Schiweck C, Valles-Colomer M, Arolt V, Muller N, Raes J, Wijkhuijs A, et al. Depression and suicidality: a link to premature T helper cell aging and increased Th17 cells. Brain Behav Immun. 2020;87:603–9. https://doi.org/10.1016/j.bbi.2020.02.005.

    Article  CAS  Google Scholar 

  37. Simon MS, Schiweck C, Arteaga-Henriquez G, Poletti S, Haarman BCM, Dik WA, et al. Monocyte mitochondrial dysfunction, inflammaging, and inflammatory pyroptosis in major depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2021;111:110391. https://doi.org/10.1016/j.pnpbp.2021.110391.

    Article  CAS  Google Scholar 

  38. Kim YK, Myint AM, Verkerk R, Scharpe S, Steinbusch H, Leonard B. Cytokine changes and tryptophan metabolites in medication-naive and medication-free schizophrenic patients. Neuropsychobiology. 2009;59(2):123–9. https://doi.org/10.1159/000213565.

    Article  CAS  Google Scholar 

  39. Linderholm KR, Skogh E, Olsson SK, Dahl ML, Holtze M, Engberg G, et al. Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia. Schizophr Bull. 2012;38(3):426–32. https://doi.org/10.1093/schbul/sbq086.

    Article  Google Scholar 

  40. Schwarcz R, Pellicciari R. Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities. J Pharmacol Exp Ther. 2002;303(1):1–10. https://doi.org/10.1124/jpet.102.034439.

    Article  CAS  Google Scholar 

  41. Kessler M, Terramani T, Lynch G, Baudry M. A glycine site associated with N-methyl-D-aspartic acid receptors: characterization and identification of a new class of antagonists. J Neurochem. 1989;52(4):1319–28.

    Article  CAS  Google Scholar 

  42. Hilmas C, Pereira EF, Alkondon M, Rassoulpour A, Schwarcz R, Albuquerque EX. The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications. J Neurosci. 2001;21(19):7463–73.

    Article  CAS  PubMed Central  Google Scholar 

  43. Kegel ME, Bhat M, Skogh E, Samuelsson M, Lundberg K, Dahl ML, et al. Imbalanced kynurenine pathway in schizophrenia. Int J Tryptophan Res. 2014;7:15–22. https://doi.org/10.4137/IJTR.S16800.

    Article  CAS  PubMed Central  Google Scholar 

  44. Gos T, Myint AM, Schiltz K, Meyer-Lotz G, Dobrowolny H, Busse S, et al. Reduced microglial immunoreactivity for endogenous NMDA receptor agonist quinolinic acid in the hippocampus of schizophrenia patients. Brain Behav Immun. 2014;41:59–64. https://doi.org/10.1016/j.bbi.2014.05.012.

    Article  CAS  Google Scholar 

  45. Benedetti F, Aggio V, Pratesi ML, Greco G, Furlan R. Neuroinflammation in Bipolar Depression. Front Psychiatry. 2020;11:71. https://doi.org/10.3389/fpsyt.2020.00071.

    Article  PubMed Central  Google Scholar 

  46. Bechter K. Schizophrenia--a mild encephalitis? Fortschr Neurol Psychiatr. 2013;81(5):250–9. https://doi.org/10.1055/s-0033-1335253.

    Article  CAS  Google Scholar 

  47. Muller N, Krause D, Dehning S, Musil R, Schennach-Wolff R, Obermeier M, et al. Celecoxib treatment in an early stage of schizophrenia: results of a randomized, double-blind, placebo-controlled trial of celecoxib augmentation of amisulpride treatment. Schizophr Res. 2010;121(1–3):118–24. https://doi.org/10.1016/j.schres.2010.04.015.

    Article  Google Scholar 

  48. Muller N, Riedel M, Schwarz MJ, Engel RR. Clinical effects of COX-2 inhibitors on cognition in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2005;255(2):149–51. https://doi.org/10.1007/s00406-004-0548-4.

    Article  Google Scholar 

  49. Laan W, Grobbee DE, Selten JP, Heijnen CJ, Kahn RS, Burger H. Adjuvant aspirin therapy reduces symptoms of schizophrenia spectrum disorders: results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2010;71(5):520–7. https://doi.org/10.4088/JCP.09m05117yel.

    Article  CAS  Google Scholar 

  50. Zheng W, Cai DB, Yang XH, Ungvari GS, Ng CH, Muller N, et al. Adjunctive celecoxib for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials. J Psychiatr Res. 2017;92:139–46. https://doi.org/10.1016/j.jpsychires.2017.04.004.

    Article  Google Scholar 

  51. Nitta M, Kishimoto T, Muller N, Weiser M, Davidson M, Kane JM, et al. Adjunctive use of nonsteroidal anti-inflammatory drugs for schizophrenia: a meta-analytic investigation of randomized controlled trials. Schizophr Bull. 2013;39(6):1230–41. https://doi.org/10.1093/schbul/sbt070.

    Article  PubMed Central  Google Scholar 

  52. Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, et 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(7):680–4. https://doi.org/10.1038/sj.mp.4001805.

    Article  CAS  Google Scholar 

  53. Kohler O, Benros ME, Nordentoft M, Farkouh ME, Iyengar RL, Mors O, et al. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry. 2014;71(12):1381–91. https://doi.org/10.1001/jamapsychiatry.2014.1611.

    Article  Google Scholar 

  54. 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(1):31–41. https://doi.org/10.1001/2013.jamapsychiatry.4.

    Article  CAS  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany

    Norbert Müller

Authors
  1. Norbert Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Norbert Müller .

Editor information

Editors and Affiliations

  1. International Institute for Brain Health, Zagreb, Croatia

    Vida Demarin

  2. Department of Neuroscience, Università di Padova, Padova, Padova, Italy

    Leontino Battistin

  3. Department of Neurology, Sveti Duh University Hospital, Zagreb, Croatia

    Hrvoje Budinčević

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Müller, N. (2023). Psychoneuroimmunology in Pula: A Hot Topic with a Long Past. In: Demarin, V., Battistin, L., Budinčević, H. (eds) Mind, Brain and Education. Springer, Cham. https://doi.org/10.1007/978-3-031-33013-1_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-33013-1_15

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-33012-4

  • Online ISBN: 978-3-031-33013-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation