Levels of soluble adhesion molecules in schizophrenia: relation to psychopathology

  • M. J. Schwarz
  • M. Riedel
  • M. Ackenheil
  • N. Müller
Part of the Key Topics in Brain Research book series (KEYTOPICS)


The intercellular adhesion molecule-1 (sICAM-1) and the vascular adhesion molecule-1 (VCAM-1) are involved in the penetration of lymphocytes through the blood-brain-barrier (BBB). Since a BBB disturbance has been observed in some schizophrenic patients, but also a lack of the CNS/peripheral immune system has been hypothesized to be involved in schizophrenia, we measured the serum levels of soluble ICAM-1 (sICAM-1) and soluble VCAM-1 (sVCAM-1) in unmedicated schizophrenic patients and the relationship to psychopathology. The results show lower levels of sICAM-1 in schizophrenics, but no difference between schizophrenics and controls regarding the sVCAM-1 levels. Patients with more pronounced negative symptoms showed higher levels of sICAM-1 and lower levels of sVCAM-1. These results point out that the ICAM-1 related adhesion system is involved in schizophrenia, while the VCAM-1 system plays a minor role. The regulatory process of antigen recognition and cellular immune activation and/or the regulation of the BBB is impaired at least in a subgroup of schizophrenic patients.


Schizophrenic Patient Soluble Adhesion Molecule Cerebral Endothelial Cell Peripheral Immune System Bioi Psychiatry 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Burkly LC, Jakubowski A, Newman BM, Rosa MD, Chi-Rosso G, Lobb RR (1991) Signaling by vascular cell adhesion molecule-1 (VCAM-1) through VLA-4 promotes CD3-dependent T cell proliferation. Eur J Immunol 21: 2871–2875PubMedCrossRefGoogle Scholar
  2. De Vries HE, Moor ACE, Blom-Roosemalen MCM, de Broer AG, Breimer DD, van Berkel TJC, Kuiper J (1994) Lymphocyte adhesion to brain capillary endothelial cells in vitro. J Neuroimmunol 52: 1–8PubMedCrossRefGoogle Scholar
  3. Fabry Z, Waldschmidt MM, Hendrickson D, Keiner J, Love-Homann L, Takei F, Hart MN (1992) Adhesion molecules on murine brain micro vascular endothelial cells: expression and regulation of ICAM-1 and Lgp 55. J Neuroimmunol 36: 1–11PubMedCrossRefGoogle Scholar
  4. Gallien M, Schnetzler JP, Morin J (1977) Antinuclear antibodies and lupus cells in 600 hospitalized phenothiazine treated patients. Ann Med Psychol Med 1: 237–248Google Scholar
  5. Hampel H, Schwarz M, Kötter HU, Schneider C, Müller N (1996) Cell adhesion molecules in the central nervous system. Drug News Perspect 9: 69–81Google Scholar
  6. Héry Ch, Sébire G, Peudenier S, Tardieu M (1995) Adhesion to human neurons and astrocytes of monocytes: the role of interaction of CR3 and ICAM-1 and modulating by cytokines. J Neuroimmunol 57: 101–109PubMedCrossRefGoogle Scholar
  7. Katila H, Appelberg B, Hurme M, Rimon R (1995) Plasma levels of Interleukin-1 beta and Interleukin-6 in schizophrenia, other psychoses, and affective disorders. Schizophr Res 12: 29–34CrossRefGoogle Scholar
  8. Kilidireas K, Latov N, Strauss DH, Gorig AD, Hashim GA, Gorman JM, Sadiq SA (1992) Antibodies to the human 60kDa heat-shock protein in patients with schizophrenia. Lancet 340: 569–572PubMedCrossRefGoogle Scholar
  9. Krenn V, Schedel J, Döring A, Huppertz HI, Gohlke F, Tony HP, Vollmers HP, Müller-Hermelink HK (1997) Endothelial cells are the major source of. sICAM-1 in rheumatoid synovial tissue. Rheumatol Int 17: 17–27PubMedCrossRefGoogle Scholar
  10. Kuhlmann P, Moy VT, Lollo BA, Brian AA (1991) The accessory function of murine intercellular adhesion molecule-1 in T-lymphocyte activation: contribution of adhesion and co-activation. J Immunol 146: 1773–1782Google Scholar
  11. Lewandowski G, Hobbs MV, Blomom FE (1994) Alteration of intracerebral cytokine production in mice infected with herpes simplex virus types I and 2. J Neuroimmunol 55: 23–34PubMedCrossRefGoogle Scholar
  12. Licinio J, Seibyl JP, Altemus M, Charney DS, Krystal JH (1993) Elevated levels of Interleukin-2 in neuroleptic-free schizophrenics. Am J Psychiatry 150: 1408–1410PubMedGoogle Scholar
  13. Marker O, Scheynius A, Christensen JP, Thomsen AR (1995) Virus-activated T cells regulate expression of adhesion molecules on endothelial cells in sites of infection. J Neuroimmunol 62: 35–42PubMedCrossRefGoogle Scholar
  14. McAllister CG, Rapaport MH, Pickar D, Podruchny TA, Christison G, Alphs LD, Paul SM (1989) Increased number of CD5+ B-lymphocytes in schizophrenic patients. Arch Gen Psychiatry 46: 890–894PubMedCrossRefGoogle Scholar
  15. McAllister CG, van Kammen DP, Rehn TJ, Miller AL, Gurklis J, Kelley ME, Yao J, Peters JL (1995) Increases in CSF levels of interleukin-2 in schizophrenia: effects of recurrence of psychosis and medication status. Am J Psychiatry 152: 1291–1297PubMedGoogle Scholar
  16. Müller N, Ackenheil M (1995) Immunoglobulin and albumin contents of cere-brospinal fluid in schizophrenic patients: the relationship to negative symptomatology. Schizophr Res 14: 223–228PubMedCrossRefGoogle Scholar
  17. Müller N, Ackenheil M (1998) Psychoneuroimmunology and the cytokine-network in the CNS: implications of psychiatric disorders. Prog Neuropsy-chopharmacol Biol Psychiatry 22: 1–33CrossRefGoogle Scholar
  18. Müller N, Ackenheil M, Hofschuster E, Mempel W, Eckstein R (1991) Cellular immunity in schizophrenic patients before and during neuroleptic therapy. Psychiatry Res 37: 147–160PubMedCrossRefGoogle Scholar
  19. Müller N, Riedel M,. Schwarz MJ, Gruber R, Ackenheil M (1997) Immuno-modulatory effects of neuroleptics to the cytokine system and the cellular immune system in schizophrenia. In: Wieselmann G (ed) Current update in psychoimmunology. Springer, Wien New York, pp 57–67CrossRefGoogle Scholar
  20. Müller N, Hadjamu M, Riedel M, Schwarz MJ, Ackenheil M, Gruber R (1999) Adhesion-molecule receptor expression on T-cells and the role of the blood-brain-barrier in schizophrenia. Am J Psychiatry 156: 634–636PubMedGoogle Scholar
  21. Özek M, Toreci K, Akkok M, Guvener Z (1971) Influence of neuroleptic therapy on antibody formation. Psychopharmacologia (Berl) 21: 401–412CrossRefGoogle Scholar
  22. Oppenheimer-Marks N, Davis LS, Bogue DT, Ramberg J, Lipsky PE (1991) Differential utilisation of ICAM-1 and VCAM-1 during the adhesion and transendothelial migration of human T-lymphocytes. J Immunol 147: 2913–2921PubMedGoogle Scholar
  23. Raine CS, Canella B, Duijvestijn AM, Cross AH (1990) Homing to central nervous vasculature by antigen-specific lymphocytes. II. Lymphocyte/ endothelial cell adhesion during the initial stages of autoimmune demyeli-nation. Lab Invest 63: 476–479PubMedGoogle Scholar
  24. Rieckmann P, Nunke K, Burchhardt M, Albrecht M, Wiltfang J (1993) Soluble intercellular adhesion molecule-1 in cerebrospinal fluid: an indicator for the inflammatory impairment of the blood-cerebrospinal fluid barrier. J Neuroimmunol 47: 133–140PubMedCrossRefGoogle Scholar
  25. Rieckmann P, Michel U, Albrecht M, Bruck W, Wockel L, Felgenhauer K (1995) Soluble forms of intercellular adhesion molecule-1 (ICAM 1) block lymphocyte attachment to cerebral endothelial cells. J Neuroimmunol 60: 9–15PubMedCrossRefGoogle Scholar
  26. Rothermund M, Arolt V, Weitzsch C, Eckhoff D, Kirchner H (1996) Production of Interferon gamma is reduced in acute schizophrenia. Biol Psychiatry 40: 1294–1296CrossRefGoogle Scholar
  27. Rothlein R, Mainolfi EA, Czajkowski M, Marlin SD (1991) A form of circulating ICAM-1 in human serum. J Immunol 147: 3788–3793PubMedGoogle Scholar
  28. Russo R, Ciminale M, Ditommaso S, Siliquini R, Zotti C, Ruggenini AM (1994) Hepatitis B vaccination in psychiatric patients. Lancet 343: 394CrossRefGoogle Scholar
  29. Schwarz MJ (1998) Die Bedeutung von Autoantikörpern gegen 60kD und 70 kD Hitzeschock-Proteine für die Pathogenese schizophrener Erkrankungen. Thesis, University of MunichGoogle Scholar
  30. Schwarz MJ, Ackenheil M, Riedel M, Müller N (1998a) Blood-CSF barrier impairment as indicator for an immune process in schizophrenia. Neurosci Lett 254: 1–3CrossRefGoogle Scholar
  31. Schwarz MJ, Riedel M, Ackenheil M, Müller N (1998b) Autoantibodies against heat shock-protein 60 in schizophrenia. Eur Arch Psychiatry Clin Neurosci 248: 282–288PubMedCrossRefGoogle Scholar
  32. Schwarz MJ, Ackenheil M, Riedel M, Müller N (1999) Soluble intercellular adhesion molecule-1 (ICAM-1) receptor levels are decreased in unmedicated and medicated schizophrenic patients. Biol Psychiatry (submitted)Google Scholar
  33. Sharief MK, Noori MA, Ciardi M, Cirelli A, Thompson EJ (1993) Increased levels of circulating ICAM-1 in serum and cerebrospinal fluid of patients with active multiple sclerosis. Correlation with TNF-alpha and blood-brain barrier damage. J Neuroimmunol 43: 15–21PubMedCrossRefGoogle Scholar
  34. Sirota P, Schild K, Elizur A, Djaldetti M, Fishman P (1995) Increased Interleukin-1 and Interleukin-3 like activity in schizophrenic patients. Prog Neuropsy-chopharmacol Biol Psychiatry 19: 75–83CrossRefGoogle Scholar
  35. Springer TA (1990) Adhesion receptors of the immune system. Nature 346: 425–434PubMedCrossRefGoogle Scholar
  36. Van Seventer GA, Shimizu Y, Horgan KJ, Shaw S (1990) The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T-cell receptor mediated activation of resting T-cells. J Immunol 144: 4579PubMedGoogle Scholar
  37. Zarrabi MH, Zucker S, Miller F, Derman RM, Romano GS, Hartnett JA, Varma AO (1979) Immunologic and coagulation disorders in chlorpromazine-treated patients. Ann Int Med 91: 194–199PubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 1999

Authors and Affiliations

  • M. J. Schwarz
    • 1
  • M. Riedel
    • 1
  • M. Ackenheil
    • 1
  • N. Müller
    • 1
  1. 1.Psychiatric HospitalLudwig-Maximilian UniversityMunichFederal Republic of Germany

Personalised recommendations