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Vol. 60, No. 1, 2009
Issue release date: September 2009

Blind Verification of Elevated Platelet Autoantibodies in Serum of Schizophrenic Patients – Part II: Adult Subjects

Spivak B. · Schechtman M. · Schönherz-Pine Y. · Blumensohn R. · Mostovoy S. · Amital D. · Deckmann M. · Weizman A. · Shinitzky M.
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Abstract

Background: In our preceding study, we assayed in a blind fashion the blood sera of young normal subjects and schizophrenic patients for levels of platelet autoantibodies (PAA). The recorded PAA titers of the schizophrenic patients were significantly higher than those of the normal subjects. This observation has lent support to this test being used as an objective evaluation of schizophrenia in young subjects in the future. In addition, this finding strongly suggested that the etiology of a distinct group of sufferers of this disorder could have originated from an autoimmune reaction against platelets which can, under certain conditions, cross-react with brain tissue. Aims: In the present study, PAA titers in the sera of adult schizophrenic patients and matched normal subjects were determined analogously to the preceding study. The effect of hospitalization and drug treatments on the apparent blood test scoring in adult subjects could thus be evaluated. Methods: A total of 46 schizophrenia patients (30 men and 16 women) aged 19–45 years (mean ± SD: 31.7 ± 8.0 years) with a minimum score of 60 on the Positive and Negative Symptom Scale and 43 healthy control subjects (22 men and 21 women) aged 21–44 years (mean ± SD: 31.9 ± 6.9 years) participated in the study. The blood titers of PAA were evaluated in a single-blind fashion using an optimized ELISA test scored by optical density (OD) units. A positive test was defined as a value above 1.3 OD units. Results: The titers of PAA in the group of schizophrenic patients (1.1 ± 0.55 OD units, range: 0.360–2.285 OD units) were significantly higher in comparison to those of the healthy control subjects (0.81 ± 0.37 OD units, range: 0.360–1.704 OD units; p = 0.004, two-tailed unpaired t-test). Significantly more schizophrenic patients showed a positive test (15 patients out of 46) than the control subjects (5 out of 43). However, significantly higher OD values of 1.55 ± 0.5 were recorded in the group of patients with less than 3 years of registered disease (n = 16, age 19–30 years), while in the group with 4–20 years of hospitalization (n = 30, age 24–45 years) the recorded OD values (0.85 ± 0.4 OD units) were practically indistinguishable from those of the control group. Conclusions: In the adult schizophrenic patients, the PAA blood test remains valid for patients who were hospitalized for less than 3 years. Drug treatment, length of disease and age can be assumed to reduce the PAA level considerably.



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References

  1. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. Washington, American Psychiatric Association, 1994.
  2. Freedman R: Schizophrenia. New Engl J Med 2003;349:1738–1749.
  3. Rupp A, Keith SJ: The costs of schizophrenia: assessing the burden. Psychiatr Clin North Am 1993;16:413–423.
  4. Kendler KS: The genetics of schizophrenia and related disorders: a review; in Dunner DL, Gershon ES, Barret JE (eds): Relatives at Risk for Mental Disorders. New York, Raven, 1988, pp 247–266.
  5. Kennedy JL, Giuffra LA, Moises HW, Cavalli-Sforza LL, Pakstis AJ, Kidd JR, et al: Evidence against linkage of schizophrenia to markers on chromosome 5 in a northern Swedish pedigree. Nature 1988;336:167–170.
  6. Sherrington R, Brynjolfsson J, Pettursson H, Potter M, Dudleston K, Barraclough B, et al: Localization of a susceptibility locus for schizophrenia on chromosome 5. Nature 1988;336:164–167.
  7. Boyd JH, Pulver AE, Stewart W: Season of birth: schizophrenia and bipolar disorder. Schizophr Bull 1986;12:173–186.
  8. Lewis SW, Murray RM: Obstetric complications, neurodevelopmental deviance and risk of schizophrenia. J Psychiatr Res 1987;21:413–421.
  9. Ganguli R, Rabin BS, Kelly RH, Lyte M, Ragu U: Clinical and laboratory evidence of autoimmunity in acute schizophrenia. Ann NY Acad Sci 1987;496:676–690.
  10. Amital H, Schoenfeld Y: Autoimmunity and schizophrenia: an epiphenomenon or an etiology. Isr J Med Sci 1993;29:593–597.
  11. Knight JG: Is schizophrenia an autoimmune disease? A review. Methods Find Exp Clin Pharmacol 1984;6:395–403.
  12. DeLisi LE, Crow TJ: Is schizophrenia a viral or immunological disorder? Psychiatr Clin North Am 1987;9:115–132.

    External Resources

  13. Abransky O, Litvin Y: Autoimmune response to dopamine-receptor as a possible mechanism in the pathogenesis of Parkinson’s disease and schizophrenia. Perspect Biol Med 1978;22:104–114.

    External Resources

  14. Knight JR: Dopamine receptor stimulating autoantibodies: a possible cause of schizophrenia. Lancet 1982;13:1073–1076.

    External Resources

  15. Sugerman AA, Southern DL, Curran JF: A study of antibody levels in alcoholic, depressive and schizophrenic patients. Ann Allergy 1982;48:166–171.
  16. Eaton WW, Byrne M, Eweld H, Mors O, Chen CY, Agerpo E, Mortensen PB: Association of schizophrenia and autoimmune diseases: linkage of Danish National registers. Am J Psychiatry 2006;163:521–528.
  17. Jones AL, Mowry BJ, Pender MP, Greer JM: Immune dysregulation and self-reactivity in schizophrenia: do some cases of schizophrenia have an autoimmune basis? Immunol Cell Biol 2005;83:9–17.
  18. Mellsop GW, Koadlow L, Syme J, Whittington S: Absence of rheumatoid arthritis in schizophrenia. Aust NZ J Med 1974;4:247–252.
  19. Ostenberg E: Schizophrenia and rheumatic disease: a study on the concurrence of inflammatory joint diseases and a review of 58 case-records. Acta Psychiatr Scand 1978;58:339–359.
  20. Allebeck P, Rodvall Y, Wistedt B: Incidence of rheumatoid arthritis among patients with schizophrenia, affective psychosis and neurosis. Acta Psychiatr Scand 1985;71:615–619.
  21. Malck-Ahmadi P: Rheumatoid arthritis and schizophrenia: are they mutually exclusive? Semin Arthritis Rheum 1985;15:70–72.
  22. Spector TD, Silman AJ: Does the negative association between rheumatoid arthritis and schizophrenia provide clues to the aetiology of rheumatoid arthritis? Br J Rheumatol 1987;26:307–310.
  23. Spector TD, Silman AJ: Rheumatoid arthritis, diabetes, and schizophrenia. Lancet 1990;335:228–229.
  24. Vinogradov S, Gottesman II, Moises HW, Nicol S: Negative association between schizophrenia and rheumatoid arthritis. Schizophr Bull 1991;17:669–678.
  25. Strous RD, Shoenfeld Y: Schizophrenia, autoimmunity and immune system dysregulation: a comprehensive model updated and revisited. J Autoimmun 2006;27:71–80.
  26. Eaton WW, Hayward C, Ram R: Schizophrenia and rheumatoid arthritis: a review. Schizophr Res 1992;6:181–192.
  27. Levine J, Susnovski M, Handzel ZT, Leykin I, Shinitzky M: Treatment of schizophrenia with an immunosuppressant. Lancet 1994;34:59–60.

    External Resources

  28. Shinitzky M, Deckman M, Kessler A, Sirota P, Rabbs A, Elizur A: Platelet autoantibodies in dementia and schizophrenia – possible implication for mental disorders. Ann NY Acad Sci 1991;621:205–217.
  29. Kessler A, Shinitzky M: Platelets from schizophrenic patients bear autoimmune antibodies that inhibit dopamine uptake. Psychobiology 1993;21:299–306.
  30. Deckmann M, Shinitzky M, Leykin I, Cheng D, Guy J, Sirota P, et al: Humoral and cellular response against autologous platelets in schizophrenia – clinical and pathophysiological implications. Ital J Psych Behav Sci 1996;6:29–34.
  31. Shinitzky M, Leykin I, Deckmann M: Autoimmunity against platelets in schizophrenia; in Shoenfeld Y (ed): The Decade of Autoimmunity. Amsterdam, Elsevier, 1999, pp 277–284.
  32. Rotman A: Blood platelets in psychopharmacological research. Prog Neuropsychopharmacol Biol Psychiatry 1983;6:135–151.

    External Resources

  33. Pletscher A: Platelets as peripheral models for neuropsychiatry: a brief review; in Racagni GEA (ed): Biological Psychiatry. Amsterdam, Elsevier, 1991, pp 354–356.
  34. Lesch KP, Wolozin BL, Murphy DL, Reiderer P: Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem 1993;6:2319–2322.

    External Resources

  35. Pletcher A, Affolter H, Cesura M, Erne E, Mueller K: Blood platelets as models for neurons: similarities of the 5-hydroxytryptamine system; in Schlossberger HG, Kochen W, Linzen B, Steinhart H (eds): Progress in Tryptophan and Serotonin Research. Berlin, De Gruyter, 1984, pp 231–239.
  36. Rotman A, Munitz H, Modai J, Tjano S, Wijsenbeck H: Comparative uptake study of serotonin, dopamine and norepinephrine by platelets of acute schizophrenic patients. Psychological Rev 1980;3:239–246.
  37. Spivak B, Schechtman M, Blumensohn R, Schönherz-Pine Y, Yoran-Hegesh R, Deckmann M, Mayer R, Weizman A, Shinitzky M: Blind verification of elevated platelet autoantibodies in serum of schizophrenic patients. Part I. Young subjects. Neuropsychobiology 2009;60:44–48.
  38. First MB, Spitzer RL, Gibbon M, et al: Structured Clinical Interview for Axis I DSM-IV Disorders, Patient Version (SCID-I/P), Version 2. New York, New York State Psychiatric Institute Biometrics Research Department, 1995.
  39. Kay S, Fiszbein A, Opler LA: The Positive and Negative Syndrome Scale for schizophrenia. Schizophr Bull 1987;13:261–276.
  40. DeLisi LE, King AC, Tagrum S: Serum immunoglobulin concentrations in patients admitted to an acute psychiatric in-patient service. Brit J Psychiatry 1984;145:661–665.
  41. Ganguli R, Rabin BS: Increased serum interleukin 2 receptor concentration in schizophrenic and brain-damaged subjects. Arch Gen Psychiatry 1989;46:292.
  42. Ganguli R, Rabin BS, Belle SH: Decreased interleukin-2 production in schizophrenic patients. Biol Psychiatry 1989;26:427–430.
  43. Wilke I, Arolt V, Rothermundt M, Weitzsch CH, Hornberg M, Kirchner H: Investigations of cytokine production in whole blood cultures of paranoid and residual schizophrenic patients. Eur Arch Psychiatry Clin Neurosci 1996;246:279–284.
  44. Ganguli R, Brar JS, Solomon W, Chengappa KN, Rabin BS: Altered interleukin-2 production in schizophrenia: association between clinical state and autoantibody production. Psychiatry Res 1992;44:113–123.
  45. Ganguli R, Brar JS, Chengappa KR, DeLeo M, Yang ZW, Shurin G, Rabin BS: Mitogen-stimulated interleukin-2 production in never-medicated, first-episode schizophrenic patients: the influence of age at onset and negative symptoms. Arch Gen Psychiatry 1995;52:668–672.
  46. Shintani F, Kanba S, Maruo N, Nakaki T, Nibuya M, Suzuki E, Kioshita N, Yagi G: Serum interleukin-6 in schizophrenic patients. Life Sci 1991;49:661–664.
  47. Vartanian ME, Kolyaskina GI, Lozovsky OV, Burbaeva GS, Ignatov SA: Aspects of humoral and cellular immunity in schizophrenia. Birth Defects Orig Artic Ser 1978;14:339–364.
  48. Chengappa KN, Ganguli R, Yang ZW, Shurin G, Brar JS, Rabin BS: Impaired mitogen (PHA) responsiveness and increased autoantibodies in Caucasian schizophrenic patients with the HLA B8/DR3 phenotype. Biol Psychiatry 1995;37:546–549.
  49. Nyland H, Naess A, Lunde H: Lymphocyte subpopulations in peripheral blood from schizophrenic patients. Acta Psychiatr Scand 1980;61:313–318.
  50. Masserini C, Vita A, Basile R, Morseli R, Boato P, Peruzzi C, Pugnetti L, Ferrante P, Cazzullo CL: Lymphocyte subsets in schizophrenic disorders: relationship with clinical, neuromorphological and treatment variables. Schizophr Res 1990;3:269–275.
  51. Coffey CE, Sullivan JL, Rice JR: T lymphocytes in schizophrenia. Biol Psychiatry 1983;18:113–119.
  52. Noy S, Achiron A, Laor N: Schizophrenia and autoimmunity – a possible etiological mechanism? Neuropsychobiology 1994;30:157–159.
  53. Heath RG, McCarron KL, O’Neil CE: Antiseptal brain antibody in IgG of schizophrenic patients. Biol Psychiatry 1989;25:725–733.
  54. Knight JG, Knight A, Menkes DB, Mullen PE: Autoantibodies against brain septal region antigens specific to unmedicated schizophrenia? Biol Psychiatry 1990;28:467–474.
  55. Henneberg AE, Horter S, Ruffert S: Increased prevalence of antibrain antibodies in the sera from schizophrenic patients. Schizophr Res 1994;14:15–22.
  56. Yang ZW, Chengappa KN, Shurin G, Brer JS, Rabin BS, Gubbi AV, Ganguli R: An association between anti-hippocampal antibody concentration and lymphocyte production of IL-2 in patients with schizophrenia. Psychol Med 1994;24:449–455.
  57. Pandey RS, Gupta AK, Chaturvedi UC: Autoimmune model of schizophrenia with special reference to antibrain antibodies. Biol Psychiatry 1981;16:1123–1136.
  58. Deckmann M, Mamillapalli R, Schechtman L, Shinitzky M: A conformational epitope which detects autoantibodies from schizophrenic patients. Clin Chim Acta 2002;322:91–98.


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