Receptor inhibition by immunoglobulins: Specific inhibition by autistic children, their relatives, and control subjects

  • Edwin H. CookJr.
  • Bruce D. Perry
  • Glyn Dawson
  • Mark S. Wainwright
  • Bennett L. Leventhal
Article

Abstract

Forty-two parents of children with autistic disorder, 15 children with autistic disorder, 17 siblings of children with autistic disorder, and 12 unrelated normal adult controls were studied to determine if immunoglobulins isolated from their plasma would inhibit binding of the 5HT 1A agonist, [ 3 H]-8-hydroxy-N,N-dipropyl-2-aminotetralin (DPAT) to 5HT 1A receptors in human hippocampal membranes. There were no significant differences among the means of percentage inhibition of DPAT binding of parents, children with autistic disorder, siblings, or unrelated controls. In addition, there were no differences in the proportion of subjects with >15% DPAT inhibition among autistic children, their parents, their siblings, or unrelated controls. Immunoglobulin inhibition was not specific for the 5HT 1A receptor binding site, since immunoglobulins inhibited binding to 5HT 2 , D 1 , D 2 , and α2-adrenergic binding sites. The immunoglobulins isolated from normal controls inhibited [ 3 H]-rauwolscine binding at α2-adrenergic sites less than immunoglobulins of children with autistic disorder and their parents and siblings. This study did not support the hypothesis that autoantibodies to 5HT 1A or 5HT 2 receptors are characteristic of autistic disorder.

Keywords

Normal Control Receptor Binding Specific Inhibition 5HT1A Receptor 5HT2 Receptor 
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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References

  1. American Psychiatric Association. (1987).Diagnostic and statistical manual of mental disorders (3rd ed., rev.). Washington, DC: Author.Google Scholar
  2. Anderson, G. M., Young, J. G., Cohen, D. J., & Schlicht, K. R. (1981). Liquidchromatographic determination of serotonin and tryptophan in whole blood and plasma.Clinical Chemistry, 27, 775–776.Google Scholar
  3. Burd, L., & Kerbeshian, J. (1988). Diagnosis of autism and other pervasive developmental disorders.Neuroscience and Biobehavioral Review, 12, 275–282.Google Scholar
  4. Cook, E. H., Leventhal, B. L., & Freedman, D. X. (1988). Free serotonin in plasma: Autistic children and their first-degree relatives.Biological Psychiatry, 24, 488–491.Google Scholar
  5. Cook, E. H., Leventhal, B. L., Heller, W., Metz, J., Wainwright, M., & Freedman, D. X. (1990). Autistic children and their first-degree relatives: Relationships between serotonin and norepinephrine levels and intelligence.Journal of Neuropsychiatry and Clinical Neurosciences, 2, 268–274.Google Scholar
  6. Creese, I., Schneider, R., & Snyder, S. H. (1977). [3 H]-Spiroperidol labels dopamine receptors in pituitary and brain.European Journal of Pharmacology, 46, 377–381.Google Scholar
  7. Crowley, S. C., & Walters, R. R. (1983). Determination of immunoglobulins in blood serum by high-performance affinity chromatography.Journal of Chromatography, 266, 157–162.Google Scholar
  8. Dahl, E. K., Cohen, D. J., & Provence, S. (1986). Clinical and multivariate approaches to the nosology of pervasive developmental disorders.Journal of the American Academy of Child Psychiatry, 25, 170–180.Google Scholar
  9. DeLong, G. R., Bean, S. C., & Brown, F. R. (1981). Acquired reversible autistic syndrome in acute encephalopathic illness in children.Archives of Neurology, 38, 191–194.Google Scholar
  10. Ferrari, P., Marescot, M. R., Moulias, R., Bursztejn, C., Deville, C. A., Thiollet, M., Lesourd, B., Braconnier, A., Dreux, C., Zarifian, E., & Fermanian, J. (1988). Etat immunitaire dans l'autisme infantile: Corrélations entre état immunitaire, symptomes autistiques et taux de sérotonine.L'Encéphale, 14, 339–344.Google Scholar
  11. Gillberg, C. (1986). Brief report: Onset at age 14 of a typical autistic syndrome. A case report of a girl with herpes simplex encephalitis.Journal of Autism and Developmental Disorders, 16, 369–375.Google Scholar
  12. Hamon, M. (1984). Radioligand binding studies: Identification of central serotonin receptors. In P. J. Marangos, I. Campbell, & R. M. Cohen (Eds.),Brain receptor methodologies-Part A: General methods and concepts, amines and acetylcholine (pp. 309–338). New York: Academic Press.Google Scholar
  13. Josic, D., Hoffman, W., Habermann, R., Schulzke, J. D., & Reutter, W. (1988). Isolation of immunoglobulins and their use in immunoaffinity HPLC.Journal of Clinical Chemistry and Clinical Biochemistry, 26, 559–568.Google Scholar
  14. Kotsopoulos, S., & Kutty, K. M. (1979). Histidinemia and infantile autism.Journal of Autism and Developmental Disorders, 9, 55–60.Google Scholar
  15. Launay, J. M., Ferrari, P., Haimart, M. D., Bursztejn, C., Tabuteau, F., Braconnier, A., Pasques, B. D., Luong, C., & Dreux, C. (1988). Serotonin metabolism and other biochemical parameters in infantile autism. A controlled study of 22 autistic children.Neuropsychobiology, 20, 1–11.Google Scholar
  16. Lotter, V. (1974). Factors related to outcome in autistic children.Journal of Autism and Childhood Schizophrenia, 4, 263–277.Google Scholar
  17. McBride, P. A., Anderson, G. M., Hertzig, M. E., Sweeney, J. A., Kream, J., Cohen, D. J., & Mann, J. J. (1989). Serotonergic responsivity in male young adults with autistic disorder.Archives of General Psychiatry.46, 205–212.Google Scholar
  18. Money, J., Bobrow, N. A., & Clarke, F. C. (1971). Autism and autoimmune disease: A family study.Journal of Autism and Childhood Schizophrenia, 1, 146–160.Google Scholar
  19. Peroutka, S. J. (1985). Selective labeling of 5-HT1A and 5-HTIB binding sites in bovine brain.Brain Research, 344, 167–171.Google Scholar
  20. Peroutka, S. J. (1987). Serotonin receptors. In H. Y. Meltzer (Ed.),Psychopharmacology: The third generation of progress (pp. 303–311). New York: Raven.Google Scholar
  21. Perry, B. D., Cook, E. H., Leventhal, B. L., Wainwright, M. S., & Freedman, D. X. (1991). Platelet 5-HT2-serotonin receptor binding sites in autistic children and their first-degree relatives.Biological Psychiatry, 30, 1–10.Google Scholar
  22. Perry, B. D., & U'Prichard, D. C. (1981).3H-Rauwolscine (alpha-yohimbine): A specific antagonist radioligand for brain alpha2-adrenergic receptors.European Journal of Pharmacology, 76, 461–464.Google Scholar
  23. Piven, J., Berthier, M. L., Starkstein, S. E., Nehme, E., Pearlson, G., & Folstein, S. (1990). Magnetic resonance imaging evidence for a defect of cerebral cortical development in autism.American Journal of Psychiatry, 147, 734–739.Google Scholar
  24. Roy, B. F., Rose, J. W., McFarland, H. F., McFarlin, D. E., & Murphy, D. L. (1986). Anti-β-endorphin immunoglobulin G in humans.Proceedings of the National Academy of Sciences of the United States of America, 83, 8739–8743.Google Scholar
  25. Sahley, T. L., & Panksepp, J. (1987). Brain opioids and autism: An updated analysis of possible linkages.Journal of Autism and Developmental Disorders, 17, 201–216.Google Scholar
  26. Sidhu, A., & Kebabian, J. W. (1985). An iodinated ligand identifying the D-1 dopamine receptor.European Journal of Pharmacology, 113, 437–440.Google Scholar
  27. Singh, V. K., Fudenberg, H. H., Emerson, D., & Coleman, M. (1988). Immunodiagnosis and immunotherapy in autistic children.Annals of the New York Academy of Sciences, 540, 602–604.Google Scholar
  28. Stubbs, E. G. (1976). Autistic children exhibit undetectable hemagglutination-inhibition antibody titers despite previous rubella vaccination.Journal of Autism and Childhood Schizophrenia, 6, 269–274.Google Scholar
  29. Stubbs, E. G., Crawford, M. L., Burger, D. R., & Vandenbark, A. A. (1977). Depressed lymphocyte responsiveness in autistic children.Journal of Autism and Childhood Schizophrenia, 7, 49–55.Google Scholar
  30. Todd, R. D., & Ciaranello, R. D. (1985). Demonstration of inter- and intraspecies differences in serotonin binding sites by antibodies from an autistic child.Proceedings of the National Academy of Sciences of the United States of America, 82, 612–616.Google Scholar
  31. Todd, R. D., Hickok, J. M., Anderson, G. M., & Cohen, D. J. (1988). Antibrain antibodies in infantile autism.Biological Psychiatry, 23, 644–647.Google Scholar
  32. Warren, R. P., Margaretten, N. C., & Foster, A. (1987). Reduced natural killer cell activity in autism.Journal of the American Academy of Child and Adolescent Psychiatry, 26, 333–335.Google Scholar
  33. Warren, R. P., Nadine, C. M., Pace, N. C., & Foster, A. (1986). Immune abnormalities in patients with autism.Journal of Autism and Developmental Disorders, 16, 189–197.Google Scholar
  34. Warren, R. P., Yonk, L. J., Burger, R. A., Cole, P., Odell, J. D., Warren, W. L., White, E., & Singh, V. K. (1990). Deficiency of suppressor-inducer (CD4+CD45RA+) T cells in autism.Immunological Investigations, 19, 245–251.Google Scholar
  35. Weizman, A., Gonen, N., Tyano, S., Szekely, G. A., & Rehavi, M. (1987). Platelet [3H]imipramine binding in autism and schizophrenia.Psychopharmacology, 91, 101–103.Google Scholar
  36. Weizman, A., Weizman, R., Szekely, G. A., Wijsenbeek, H., & Livni, E. (1982). Abnormal immune response to brain tissue antigen in the syndrome of autism.American Journal of Psychiatry, 139, 1462–1465.Google Scholar
  37. Yuwiler, A., & Freedman, D. X. (1987). Neurotransmitter research in autism. In E. Schopler (Ed.),Neurobiological issues in autism (pp. 263–283). New York: Plenum Press.Google Scholar
  38. Yuwiler, A., Shih, J. C., Chen, C.-H., Ritvo, E. R., Hanna, G., Ellison, G. W., & King, B. H. (1992). Hyperserotoninemia and antiserotonin antibodies in autism and other disorders.Journal of Autism and Developmental Disorders, 22, 33–45.Google Scholar

Copyright information

© Plenum Publishing Corporation 1993

Authors and Affiliations

  • Edwin H. CookJr.
    • 1
  • Bruce D. Perry
    • 1
  • Glyn Dawson
    • 2
  • Mark S. Wainwright
    • 1
  • Bennett L. Leventhal
    • 1
  1. 1.Child and Adolescent Psychiatry, Department of PsychiatryUniversity of ChicagoChicago
  2. 2.Department of Pediatrics and Pharmacology and PhysiologyUniversity of ChicagoChicagoUSA

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