Journal of Clinical Immunology

, Volume 14, Issue 1, pp 73–78

Anticardiolipin antibodies are elevated in drug-free, multiply affected families with schizophrenia

  • Michael Firer
  • Pinkhas Sirota
  • Klara Schild
  • Avner Elizur
  • Hanoch Slor
Original Articles


The objective of this study was to measure anticardiolipin antibodies in patients and healthy relatives in multicase families with schizophrenia. Twenty-eight (28) multicase families with schizophrenia were examined. One hundred three drug-free patients and 66 first-degree relatives consented to evaluation by DSM-III-R criteria. Criteria for patient definition included the following: age ≥16, a confirmed hospital diagnosis of schizophrenia, knowledge of biological parents, and consent to participate. Additional data were drawn from family history and medical records. Serum samples were tested separately for IgG and IgM anticardiolipin by enzyme-linked immunosorbent assay (ELISA) and designated positive/negative by comparison to the reactivity of an age-matched control group. IgG anticardiolipin antibodies were significantly more common in both patients and relatives compared to controls. IgM anticardiolipin antibodies were significantly more common in patients. In 75% of families at least one member was anticardiolipin positive and this positivity correlated with patient positivity. The relevance of anticardiolipin antibodies in both patients and healthy relatives of some multicase families to the pathogenesis of schizophrenia is discussed.

Key words

Anticardiolipin schizophrenia multicase families autoimmune disease enzyme-linked immunosorbent assay (ELISA) 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Sirota P: Is schizophrenia an autoimmune disease? Isr J Med Sci 26:694–697, 1990PubMedGoogle Scholar
  2. 2.
    Sirota P, Firer MA, Schild K, Zurgil N, Barak Y, Slor H: (1993). Anti-Sm antibodies are elevated in patients with schizophrenia and their first degree relatives. Prog Neuropharm Biol Psychiat (in press)Google Scholar
  3. 3.
    Sirota P, Firer MA, Schild K, Amir T, Avner E, Meytes D, Slor H: Autoantibodies to DNA in multicase families with schizophrenia. Biol Pysch 33:450–455Google Scholar
  4. 4.
    Ganguli R, Rasin BS, Kelly RH: Multiple autoantibodies and autoimmune disease in schizophrenic patients: Evidence for an autoimmune pathogenesis. In Interactions Among CNS, Neuroendocrine and Immune Systems, JW Hadden, K Masek, G Nistico (eds). Pythagora Press, 1989, p 365Google Scholar
  5. 5.
    Zarrabi MH, Zucker S, Miller F: Immunologic and coagulation disorders in chlorpromazine treated patients. Ann Intern Med 91:194–196, 1979PubMedGoogle Scholar
  6. 6.
    Von Brauchitsch H: Antinuclear factor in psychiatric disorders. Am J Psychiat 128:4552–4555, 1972Google Scholar
  7. 7.
    Harris EN, Asherson RA, Hughes GRV: Antiphospholipid antibodies: Autoantibodies with a difference. Annu Rev Med 39:261–267, 1988PubMedGoogle Scholar
  8. 8.
    Alarcon-Segovia D: Pathogenic potential of antiphospholipid antibodies. J Rheumatol 15:890–893, 1989Google Scholar
  9. 9.
    Sammaritano LR, Gharavi AG, Lockshin MD: Antiphospholipid syndrome: Immunological and clinical aspects. Semin Arth Rheum 20:81–88, 1990Google Scholar
  10. 10.
    McNeil HP, Hunt JE, Krilis SA: Antiphospholipid antibodies—new insights into their specificity and clinical importance. Scand J Immunol 36:647–652, 1992PubMedGoogle Scholar
  11. 11.
    Asherson RA: Antiphospholipid antibodies and “syndromes”: Many questions and few answers. Isr J Med Sci 26:284–286, 1990PubMedGoogle Scholar
  12. 12.
    Canoso RT, Sise HS: Chlorpromazine-induced lupus anticoagulant and associated immunologie abnormalities. Am J Haematol 113:121–125, 1982Google Scholar
  13. 13.
    Manoussakis MV, Gharavi AE, Droses AA, Kitridou RG, Moutsopoulas HM: Anticardiolipin antibodies in unselected autoimmune rheumatic disease patients. Clin Immunol Immunopathol 44:297–303, 1987PubMedGoogle Scholar
  14. 14.
    Manoussakis MN, Tzioufas AG, Silus MP, Pange PJE, Goudevenbos J, Moutsopoulos HM: High prevalence of anti-cardiolipin and other autoantibodies in healthy elderly patients. Clin Exp Immunol 69:557–563, 1987PubMedGoogle Scholar
  15. 15.
    Yannitsi SG, Manoussakis MN, Mavridis AK: Factors related to the presence of autoantibodies in patients with chronic mental disorders. Biol Psychiat 27:747–751, 1990PubMedGoogle Scholar
  16. 16.
    Canoso RT, de Oliveira RM, Nixon RA: Neuroleptic-associated autoantibodies. A prevalence study. Biol Psychiat 27:863–888, 1990PubMedGoogle Scholar
  17. 17.
    Chengappa KNR, Carpentor AB, Keshavan MS, Yang ZW, Kelly RH, Rabin BS, Ganguli R: Elevated IgG and IgM anticardiolipin antibodies in a subgroup of medicated and unmedicated schizophrenics. Biol Psychiat 30:731–735, 1991PubMedGoogle Scholar
  18. 18.
    Evaes L, Schulz SC, Sharp R: Genetics, immunology and virology. Schizo Bull 14:305–311, 1988Google Scholar
  19. 19.
    American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders (ed 3 rev) (DSM-3-R). APA, Washington, DC, 1987Google Scholar
  20. 20.
    Endicott J, Spitzer R: A diagnostic interview: The schedule for affective disorders and schizophrenia. Arch Gen Psychiat 35:837–844, 1979Google Scholar
  21. 21.
    Firer MA, Spivak T, Shoenfeld Y, Slor H: The effect of incubation temperature and coating procedure on the measurement of antibodies to cardiolipin. J Immunol Methods 143:31–38, 1991PubMedGoogle Scholar
  22. 22.
    Harris EN: The Second International Anti-Cardiolipin Standardization Workshop/The Kingston Anti-Phospholipid Antibody Study (KAPS) Group. Am J Clin Pathol 94:476–484, 1990PubMedGoogle Scholar
  23. 23.
    Zucker S, Zarrabi MH, Romano GS, Miller F: IgM inhibitor of the contract activation phase of coagulation in chlorpro-mazine-treated patients. Br J Haematol 40:441–445, 1978Google Scholar
  24. 24.
    Rotrosen J, Nolkin A: Phospholipid and prostaglandin hypothesis of schizophrenia. In Psychopharmacology: The Third Generation of Progress, HV Meltzer (ed). New York, Raven Press, 1987, p 759Google Scholar
  25. 25.
    Keshavan MS, Pettegren JW, Panchalingam K: In vivo 31P nuclear magnetic resonance (NMR) spectroscopy of the frontal lobe metabolism in neuroleptic-naive first episode psychoses. Preliminary studies. Schizo Res 2:122, 1989 (abstr)Google Scholar
  26. 26.
    McNeil HP, Hunt JE, Krillis SA: New aspects of anticardiolipin antibodies. Clin Exp Rheumatol 8:525–527, 1990PubMedGoogle Scholar
  27. 27.
    Tomer Y, Buskila D, Shoenfeld Y: Pathogenic significance and diagnostic value of lupus autoantibodies. Int Arch Allergy Immunol 100:293–306, 1993PubMedGoogle Scholar
  28. 28.
    McNeil HP, Simpson RJ, Chesterman CN, Krillis SA: Antiphospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: Beta-2-glycoprotein 1 (apolipoprotein H). Proc Natl Acad Sci USA 87:4120–4124, 1990PubMedGoogle Scholar
  29. 29.
    Galli M, Comfurius P, Maassen C: Anticardiolipid antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 336:177–178, 1990Google Scholar
  30. 30.
    Harris EN, Pierangeli S, Barquinero J, Ordi-Ros J: Anticardiolipin antibodies and binding of anionic phospholipids and serum protein. Lancet 336:505–506, 1990PubMedGoogle Scholar
  31. 31.
    Gharavi AE, Sammaritano LR, Morse JH, Zarrabi MH, Lockshin MD: Binding characteristics of HIV and chlorpromazine-induced anti-phospholipid antibodies. Arth Rheum 36:R34, 1993Google Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Michael Firer
    • 1
  • Pinkhas Sirota
    • 2
    • 3
  • Klara Schild
    • 2
    • 3
  • Avner Elizur
    • 2
    • 3
  • Hanoch Slor
    • 3
  1. 1.Biohytech (Israel) Ltd.ArielIsrael
  2. 2.Abarbanel Mental Health CenterBat YamIsrael
  3. 3.Department of Human Genetics, Sackler School of MedicineTel Aviv UniversityIsrael
  4. 4.School of Engineering and Research InstituteTechnical College of Judea & SamariaArielIsrael

Personalised recommendations