A preliminary analysis investigating immune activation in schizophrenia

  • M. H. Rapaport
  • M. P. Caliguiri
  • J. B. Lohr
  • D. Dolnak
  • S. Chavez
  • C. Kulesh
  • T. Hahn
Conference paper
Part of the Key Topics in Brain Research book series (KEYTOPICS)


This paper is an interrum analysis of a longitudinal project designed to ascertain whether immune activation is a trait marker for a small subset of patients with the syndrome we call schizophrenia. We present data from over 70 schizophrenic patients and 50 matched normal volunteers. The patients were evaluated on 2 occasions at least 30 days apart. The preliminary analyses suggest that some patients with schizophrenia may have an immune modulated component to their disorder and this seems to be a relatively stable trait marker of the syndrome for these patients.


Immune Activation Schizophrenic Patient Wrist Flexion Soft Neurological Sign Schizophrenic Subject 
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.


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  1. 1.
    Swedo S, Rapoport J, Cheslow B, et al. (1989) High prevalence of obsessive-compulsive symptoms in patients with Sydenham’ Chorea. Am J Psychiatry 146: 246–249PubMedGoogle Scholar
  2. 2.
    Sindic CJ, Laterre EC (1990) Oligoclonal free kappa and lambda bands in the cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. An immunoaffinity-mediated capillary blot study. J Neuroimmunol 33: 63–72CrossRefGoogle Scholar
  3. 3.
    Van Dam AP (1991) Diagnosis and pathogenesis of CNS lupus. Rheumatol Int 11: 1–11PubMedCrossRefGoogle Scholar
  4. 4.
    Rapaport MH, McAllister CG (1991) Neuroimmunologic factors in schizophrenia. In: Gorman J, Kertzner R (eds) Psychoimmunology update. American Psychiatric Press, Washington, DC, pp 31–47Google Scholar
  5. 5.
    Lehman-Facius H (1939) Serologisch-analytisch Verche mit Liquoren und Seren von Schizophrenien. Alg Z Psychiatr 110: 232–243Google Scholar
  6. 6.
    Johnstone E, Whaley K (1975) Antinuclear antibodies in psychiatric illness: their relationship to diagnosis and drug treatment. Br Med J 724–725Google Scholar
  7. 7.
    Kronfol Z, Turner R, Nasrallah H, et al. (1984) Leukocyte regulation in depression and schizophrenia. Psychiatry Res 13: 13–18PubMedCrossRefGoogle Scholar
  8. 8.
    Liedman R, Prilipko L (1978) The behavior for lymphocytes in schizophrenia. Original Article Series XIV, No 5: 365–377Google Scholar
  9. 9.
    Villemain F, Chatenoud L, Guillibert E, et al. (1987) Decreased production of interleukin-2 in schizophrenia. Ann NY Acad Sci 496: 669–675PubMedCrossRefGoogle Scholar
  10. 10.
    Villemain F, Chatenoud L, Galinowski A, et al. (1989) Aberrant T-cell-medi-ated immunity in untreated schizophrenic patients: deficient interleukin-2 production. Am J Psychiatry 146: 609–616PubMedGoogle Scholar
  11. 11.
    Ganguli R, Rabin BS, Belle SH (1989) Decreased interleukin-2 production in schizophrenic patients. Biol Psychiatry 26: 427–430PubMedCrossRefGoogle Scholar
  12. 12.
    Shintani F, Kanba S, Maruo N, et al. (1991) Serum interleukin-6 in schizophrenic patients. Life Sci 49: 661–664PubMedCrossRefGoogle Scholar
  13. 13.
    Maes M, Meltzer H, Bosnians E (1994) Immune-inflammatory markers in schizophrenia: comparison to normal controls and effects of clozapine. Acta Psychiatr Scand 3: 4–6Google Scholar
  14. 14.
    Katila H, Appelberg B, Hurme M, et al. (1995) Plasma levels of interleukin-1 b and interleukin-6 in schizophrenia, other psychoses, and affective disorders. Schizophr Res 12: 29–34CrossRefGoogle Scholar
  15. 15.
    Hornberg M, Arolt V, Wilke I, et al. (1995) Production of interferons and lymphokines in leukocyte cultures of patients with schizophrenia. Schizophr Res 15: 237–242PubMedCrossRefGoogle Scholar
  16. 16.
    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 244: 325–329.Google Scholar
  17. 17.
    Muller N, Manfred A, Hofschuster E, Mempel W, Eckstein R (1991) Cellular immunity in schizophrenic patients before and during neuroleptic treatment. Psychiatry Res 37: 147–160PubMedCrossRefGoogle Scholar
  18. 18.
    Maes M, Bosmans E, Calabrese J, Smith R, Meltzer HY (1995) Interleukin-2 and interleukin-6 and mania: effects of neuroleptics and mood stabilizers. J Psychiat Res 29(2): 141–152PubMedCrossRefGoogle Scholar
  19. 19.
    Rapaport MH (1994) Immune parameters in euthymic bipolar patients and normal volunteers. J Affect Disord 32: 149–156PubMedCrossRefGoogle Scholar
  20. 20.
    Rapaport MH, Stein MB (1994) Serum interleukin-2 and soluble interleukin-2 receptor in generalized social phobia. Anxiety 1: 50–53PubMedGoogle Scholar
  21. 21.
    Maes M, Stevens W, Scharpe S, et al. (1994) Seasonal variation in peripheral blood leukocyte subsets and in serum interleukin-6, and soluble interleukin-2 and-6 receptor concentrations in normal volunteersGoogle Scholar
  22. 22.
    Rubin LA, Nelson DL (1990) The soluble interleukin-2 receptor: biology, function and clinical application. Ann Intern Med 113: 619–627PubMedGoogle Scholar
  23. 23.
    Barbanel G, Ixart G, Szafarczyk A, et al. (1990) Intrahypothalamic infusion of interleukin-b increases the release of corticotropin-releasing hormone (CRH 41) and adrenocorticotropic hormone (ACTH) in free-moving rats bearing a push-pull cannula in the median eminence. Brain Res 516: 31–36PubMedCrossRefGoogle Scholar
  24. 24.
    Nistico G, De Sarro G (1991) Is interleukin-2 a neuromodulator in the brain? TINS 14: 146–150PubMedGoogle Scholar
  25. 25.
    Besedowsky H, Del Rey A, Sorkin E et al. (1983) The immune response evokes changes in brain noradrenergic neurons. Science 221: 564–566CrossRefGoogle Scholar
  26. 26.
    Lapchak PA (1992) A role for interleukin-2 in the regulation of striatal dopaminergic function. Neuroreport 3: 165–168PubMedCrossRefGoogle Scholar
  27. 27.
    Lapchak PA, Araujo DM (1993) Interleukin-2 regulates monoamine and opioid peptide release from the hypothalamus. Neuroreport 4: 303–306PubMedCrossRefGoogle Scholar
  28. 28.
    Lapchak PA, Araujo DM, Quirion R, et al. (1991) Immunoradiographic localization of interleukin 2-like immunoreactivity and interleukin 2 receptors (Tac antigen-like immunoreactivity) in the rat brain. Neuroscience 44: 173–184PubMedCrossRefGoogle Scholar
  29. 29.
    Saper CB, Breder CD The neurologic basis of fever. N Engl J Med 330: 1880–1886Google Scholar
  30. 30.
    Banks WA, Ortiz L, Plotkin R et al. (1990) Human interleukin (IL) la, murine IL-la and murine IL-lb are transported form blood to brain in the mouse by a shared saturable mechanism. J Pharmacol Exp Ther 259: 988–996Google Scholar
  31. 31.
    Waguespack P, Banks W, Kastin A (1993) Interleukin-2 does not cross the blood-brain barrier by a saturable transport system. Brain Res Bull 34: 103–109CrossRefGoogle Scholar
  32. 32.
    McAllister C, Konicki E, Kirch D, et al. (1991) Increased percentage of T-lymphocytes in CSF of schizophrenic patients. Schizophr Res 4: 373CrossRefGoogle Scholar
  33. 33.
    Mittleman BB, Castellanos FX, Jacobsen LK, Rapoport JL, Swedo SE, Shearer GM (1997) Cerebrospinal fluid cytokines in pediatric neuropsychiatric disease. J Immunol 159: 2994–2999PubMedGoogle Scholar
  34. 34.
    Durham S, Ying S, Varney V, et al. (1992) Cytokine messenger RNA expression for IL-3, IL-4, IL-5, and granulocyte/macrophage-colony stimulating factor in the nasal mucosa after local allergen provocation: relationship to tissue rosinophilia. J Immunol 148: 2390–2394PubMedGoogle Scholar
  35. 35.
    Psicopoulos A, Hamid W, Varney V (1992) Preferential messenger RNA expression of TH1 type cells (IFN-gamma, IL-2+) in classical delayed-type (tuberculin) hypersensitivity reactions in human skin. J Immunol 148: 2058–2061Google Scholar
  36. 36.
    Earronichi P, Macchia D, Piccinni M (1991) Allergen and bacterial antigen-specific T-cell clones established form atopic donors show a different profile of cytokine production. Proc Natl Acad Sci USA 88: 4538–4542CrossRefGoogle Scholar
  37. 37.
    Licinio J, Seibyl JP, Altemus M, et al (1998) Elevated CSF levels of interleukin-2 in neuroleptic-free schizophrenic patients. Am J Psychiatry 150: 1408–1410Google Scholar
  38. 38.
    Denicoff KD, Rubinow DR, Papa MZ, Simpson C, Seipp CA, Lotze MR, Change AE, Rosenstein D, Rosenberg SA (1987) The neuropsychiatrie effects of treatment with interleukin-2 and lymphokine activated killer cells. Ann Intern Med 107: 293–300PubMedGoogle Scholar
  39. 39.
    Rapaport MH, Lohr JB (1994) Serum interleukin-2 receptors in neuroleptic naïve schizophrenic subjects and in medicated schizophrenic subjects with and without tardive dyskinesia. Acta Psychiatr Scand 90: 311–315PubMedCrossRefGoogle Scholar
  40. 40.
    Rapaport MH, Caliguiri MP, Lohr JB (1997) An association between increased serum soluble interleukin-2 receptors and a disturbance in motor muscle force in schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry 21(5): 817–827PubMedCrossRefGoogle Scholar
  41. 41.
    Schmidt RA, Zelaznik HN, Hawkins B, et al. (1979) Motor output variability: a theory for the accuracy of rapid motor acts. Psychol Rev 86: 415–451CrossRefGoogle Scholar
  42. 42.
    Schmidt RA (1982) Motor control and learning. University of Illinois Press, Champaign, ILGoogle Scholar
  43. 43.
    Bizzi E, Polit A, Morasso P (1976) Mechanisms underlying the achievement of final head position. J Neurophysiol 39: 435–444PubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 1999

Authors and Affiliations

  • M. H. Rapaport
    • 1
  • M. P. Caliguiri
    • 1
  • J. B. Lohr
    • 1
  • D. Dolnak
    • 1
  • S. Chavez
    • 1
  • C. Kulesh
    • 1
  • T. Hahn
    • 1
  1. 1.Department of PsychiatryU.C. San Diego School of Medicine and the San Diego Veterans’Affairs Health SystemSan DiegoUSA

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