Advertisement
Research Article| Volume 30, ISSUE 2, P121-130, July 15, 1991

Platelet 5-HT2 serotonin receptor binding sites in autistic children and their first-degree relatives

  • Bruce D. Perry
    Correspondence
    Address reprint request to Bruce D. Perry, Ph.D., Laboratory of Developmental Neurosciences, Department of Psychiatry Box 411, The University of Chicago, Chicago, IL 60637.
    Footnotes
    Affiliations
    Section of Child and Adolescent Psychiatry, Departments of Psychiatry and Pediatrics, The University of Chicago, Chicago, IL 60637, USA
    Search for articles by this author
  • Edwin H. Cook Jr.
    Footnotes
    Affiliations
    Section of Child and Adolescent Psychiatry, Departments of Psychiatry and Pediatrics, The University of Chicago, Chicago, IL 60637, USA
    Search for articles by this author
  • Bennett L. Leventhal
    Footnotes
    Affiliations
    Section of Child and Adolescent Psychiatry, Departments of Psychiatry and Pediatrics, The University of Chicago, Chicago, IL 60637, USA
    Search for articles by this author
  • Mark S. Wainwright
    Footnotes
    Affiliations
    Section of Child and Adolescent Psychiatry, Departments of Psychiatry and Pediatrics, The University of Chicago, Chicago, IL 60637, USA
    Search for articles by this author
  • Daniel X. Freedman
    Footnotes
    Affiliations
    Neuropsychitric Institute, University of California, Los Angeles, CA, USA
    Search for articles by this author
  • Author Footnotes
    ∗ The autors would like to thank the local chapters of the National Society for Autistic Citizens and the families participating in the present studies. Dr. Judith Wopner provided laboratory facilities for samples collected and processed in Indianapolis.Domenico Vigilante and Zheng L: provided expert technical assistance. Technical support was provided by Erik Kupperman, Joseph Cuenco, Grace Lay, and Steve Dayan. Matthew Leventhal assisted in blood collection.
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      We examined platelet serotonin2 [5-hydroxytryptamine2 (5-HT2)] receptor binding sites, whole blood serotonin (5-HT), and plasma norepinephrine (NE) in male autistic children and their first-degree relatives. Saturation studies utilizing 125I-spiroperidol labeled the 5-HT2 sites with an affinity of 224.6 ± 84.4 pmol/L (Kd). No group differences, i.e., autistic (n = 12), siblings (n = 6), parents (n = 22), control (adult; n = 7: child; n = 10), were seen for either the Kd or the total number of sites (Bmax: 14.3 ± 10.9 fmol/mg protein). No correlations were found in any group between binding parameters (Kd or Bmax) and whole blood 5-HT. For the parental group, inverse correlations were found between NE and Bmax standing NE,rs = − 0.67, n = 21, p = 0.001; supine NE, rs = − 0.49, n = 22, p = 0.021). In the autistic group, no correlation was seen between plasma NE and Bmax. A correlation between the autistic boys' Bmax and their fathers' Bmax was observed (rs = 0.79, n = 11, p = 0.004). These findings suggest
      • 1.
        (1) circulating NE may be involved in heterologous regulation of 5-HT2 receptors in the platelet and
      • 2.
        (2) genetic (paternal-filial) factors may play a role in the expression of 5-HT2 binding sites in the platelet.
      These preliminary findings are discussed in relation to heterologous receptors regulation. The relationships between these findings and either the pathophysiology of autism or hyperserotonemia in autism are unknown.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • American Psychiatric Association, Committee on Nomenclature and Statistics
        Diagnostic and Statistical Manual of Mental Disorders.
        in: 3rd ed rev. American Psychiatric Press, Washington, DC1987
        • Anderson G.M.
        • Young J.G.
        • Cohen D.J.
        • Schlicht K.R.
        • Patel N.
        Liquid-chromatographic determination of serotonin and tryptophan in whole blood and plasma.
        Clin Chem. 1981; 27: 775
        • Anderson G.M.
        • Feibel F.C.
        • Cohen D.J.
        Determination of serotonin in whole blood, platelet-rich plasma, platelet-poor plasma, and plasma ultrafiltrate.
        Life Sci. 1987; 40: 1063-1070
        • Anderson G.M.
        • Freedman D.X.
        • Cohen D.J.
        • et al.
        Whole blood serotonin in autistic and normal subjects.
        J Child Psychol Psychiatry. 1987; 28: 885-900
        • Cook E.H.
        • Leventhal B.L.
        • Freedman D.X.
        Free serotonin in plasma: Austistic children and their first-degree relatives.
        Biol Psychiatry. 1988; 24: 488-491
        • Cook E.H.
        • Leventhal B.L.
        • Heller W.
        • Metz J.
        • Wainwright M.
        Autistic children and their first-degree relatives: Relationships between serotonin and norepinephrine levels andintelligence.
        J Neuropsychiatry Clin Neurosci. 1990; 2: 268-274
        • Dunn L.M.
        Peabody Picture Vocabulary Test-Revised.
        American Guidance Service, Circle Pines, MN1981
        • Hamon M.
        Radioactive ligand binding studies: Identification of central serotonin receptor.
        in: Brain Receptor Methodologies. vol 1. Academic, New York1984: 309-335
        • Harden K.
        Agonist induced desensitization of the beta-adrenergic receptor-linked adenylate cyclase.
        Pharmacol Rev. 1983; 35: 5-32
        • Hoffmann B.B.
        • Mullkin-Kilpatrick D.
        • Lefkowitz R.J.
        Heterogeneity of radioligand binding to alpha-adrenergic receptors: Analysis of guanine nucleotide regulation of agonist binding in relation to receptor subtypes.
        J Biol Chem. 1980; 255: 4645-4650
        • Hollingshead A.B.
        • Redlich F.
        Social Class and Mental Illness.
        Wiley, New York1958
        • Kuperman S.
        • Beeghly J.H.
        • Burns T.L.
        • Tsai L.Y.
        Serotonin relationships of autistic probands and their first-degree relatives.
        J Am Acad Child Adolesc Psychiatry. 1985; 24: 186-190
        • Leventhal B.L.
        • Cook E.H.
        • Morford M.
        • Ravitz A.
        • Freedman D.X.
        Relationships of whole blood serotonin plasma and norepinephrine within families of autistic children.
        J Austin Devel Disord. 1990; 20: 499-511
        • Limbird L.
        Receptors linked to inhibition of adenylate cyclase: Additional signaling mechanisms.
        FASEB J. 1988; 2: 2686-2695
        • Maggi A.
        • U'Prichard D.C.
        • Enna S.J.
        Beta-adrenergic regulation of alpha2-adrenergic receptors in the central nervous system.
        Science. 1980; 207: 645-647
        • McBride P.A.
        • Anderson G.M.
        • Hertzig M.E.
        • et al.
        Serotonergic responsivity in male young adults with autistic disorder: Results of a pilot study.
        Arch Gen Psychiatry. 1989; 46: 213-221
        • McPherson G.A.
        Analysis of radioligand binding experiments: A collection of computer programs for the IBM-PC.
        J Pharmacol Methods. 1985; 14: 213-228
        • Mefford I.N.
        • Ward M.M.
        • Miles L.
        • et al.
        Determination of plasma catecholamines and free 3,4-dihydroxyphenolacetic acid in continuously collected human plasma by high performance liquid chromatography with electrochemical detection.
        Life Sci. 1981; 28: 477-483
        • Munson P.J.
        • Rodbard D.
        LIGAND: A versatile computerized approach for the characterization of ligand binding systems.
        Anal Biochem. 1980; 107: 220-239
        • Perry B.D.
        Homeostasis and dysregulation of blood element adrenergic receptors: A model for examining parameters of membrane receptor functioning in psychiatric populations.
        Soc Neurosci Abstr. 1986; 12: 414
        • Perry B.D.
        Placental and blood element neurotransmitter receptor regulation in humans: Potential models for studying neurochemical and mechanisms underlying behavioral teratology.
        Prog. Brain Res. 1988; 73: 189-205
        • Schain R.J.
        • Freedman D.X.
        Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children.
        J Pediatr. 1961; 58: 315-320
        • Scott J.A.
        • Crews F.T.
        Increase in serotonin2 receptor density in rat cerebral cortex slices by stimulation of beta-adrenergic receptors.
        Biochem Pharmacol. 1985; 34: 1585-1588
        • Todd R.D.
        • Ciaranello R.D.
        Demonstration of inter- and intraspecies differences in serotonin binding sites by antibodies from an autistic child.
        in: Proc Natl Acad Sci (USA). 82. 1985: 612-616
        • Wechsler D.
        Manual for the Wechsler Preschool and Primary Scale of Intelligence. The Psychological Corporation, New York1967
        • Wechsler D.
        Manual for the Wechsler Intelligence Scale for Children—Revised. The Psychological Corporation, New York1974
        • Wechsler D.
        Manual for the Wechsler Adult Intelligence Scale—Revised. The Psychological Corporation, 1981
        • Yuwiler A.
        • Freedman D.X.
        Neurotransmitter research in autism.
        in: Schopler E. Mesibov G.B. Neurobiological Issues in Autism. Plenum, New York1987: 263-284