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, [3H]-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 [3H]-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.
References
American Psychiatric Association. (1987).Diagnostic and statistical manual of mental disorders (3rd ed., rev.). Washington, DC: Author.
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.
Burd, L., & Kerbeshian, J. (1988). Diagnosis of autism and other pervasive developmental disorders.Neuroscience and Biobehavioral Review, 12, 275–282.
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.
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.
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.
Crowley, S. C., & Walters, R. R. (1983). Determination of immunoglobulins in blood serum by high-performance affinity chromatography.Journal of Chromatography, 266, 157–162.
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.
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.
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.
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.
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.
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.
Kotsopoulos, S., & Kutty, K. M. (1979). Histidinemia and infantile autism.Journal of Autism and Developmental Disorders, 9, 55–60.
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.
Lotter, V. (1974). Factors related to outcome in autistic children.Journal of Autism and Childhood Schizophrenia, 4, 263–277.
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.
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.
Peroutka, S. J. (1985). Selective labeling of 5-HT1A and 5-HTIB binding sites in bovine brain.Brain Research, 344, 167–171.
Peroutka, S. J. (1987). Serotonin receptors. In H. Y. Meltzer (Ed.),Psychopharmacology: The third generation of progress (pp. 303–311). New York: Raven.
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.
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.
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.
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.
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.
Sidhu, A., & Kebabian, J. W. (1985). An iodinated ligand identifying the D-1 dopamine receptor.European Journal of Pharmacology, 113, 437–440.
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.
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.
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.
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.
Todd, R. D., Hickok, J. M., Anderson, G. M., & Cohen, D. J. (1988). Antibrain antibodies in infantile autism.Biological Psychiatry, 23, 644–647.
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.
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.
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.
Weizman, A., Gonen, N., Tyano, S., Szekely, G. A., & Rehavi, M. (1987). Platelet [3H]imipramine binding in autism and schizophrenia.Psychopharmacology, 91, 101–103.
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.
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.
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.
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Cook, E.H., Perry, B.D., Dawson, G. et al. Receptor inhibition by immunoglobulins: Specific inhibition by autistic children, their relatives, and control subjects. J Autism Dev Disord 23, 67–78 (1993). https://doi.org/10.1007/BF01066419
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DOI: https://doi.org/10.1007/BF01066419