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Pharmacopsychiatry 2000; 33(5): 165-168
DOI: 10.1055/s-2000-7588
Original Paper
ORIGINALARBEIT
© Georg Thieme Verlag Stuttgart · New York

Increased Density of the Platelet Serotonin Transporter in Autism

D. Marazziti1 , F. Muratori2 , A. Cesari2 , I. Masala1 , S. Baroni1 , G. Giannaccini1 , L. Dell'Osso1 , A. Cosenza2 , P. Pfanner2 , G. B. Cassano1
  • 1Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie
  • 2Scientific Institute Stella Maris, Division of Child Psychiatry, University of Pisa, Italy
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Publication History

Publication Date:
31 December 2000 (online)

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Background: Various data have shown the involvement of serotonin (5-HT) in autism. The presence of the 5-HT transporter in platelets, similar to the same structure located in presynaptic serotonergic neurons, has produced a series of studies aimed at assessing its functionality in this disorder, but the ensuing findings are quite controversial. For this reason, we investigated the 5-HT transporter by means of the specific binding of [3H]-Paroxetine ([3H]-Par), which is currently considered the first-choice ligand for labeling it, in platelets of 20 autistic children and adolescents, as compared with healthy control subjects. Methods: Twenty children and adolescents of both sexes suffering from autism according to DSM IV criteria were included in the study and compared with a similar group of healthy control subjects. Platelet membranes and the binding of [3H]-Par were carried out according to standardized protocols. Results: The results showed a significantly higher density of [3H]-Par binding sites in autistic children than in healthy control subjects. Conclusions: These findings support the presence of a serotonergic dysfunction in autism and would suggest that the 5-HT transporter may have a specific role in this disorder, also in the light of its recently proposed role in brain development.

References

  • 1 American Psychiatric Association Committee on Nomenclature and Statistics .Diagnostic and Statistical Manual for Mental Disorders. American Psychiatric Press Washington, D.C; 1994 Fourth Edition
    Google Scholar
  • 2 Anderson G M, Minderaa R B, van Benthem P G, Volkmar F R, Cohen D J. Platelet imipramine binding in autistic subjects.  Psychiatry Res. 1984;  11 133-141
    CrossrefPubMedGoogle Scholar
  • 3 Azmitia E C, Whitaker-Azmitia P M. Development and adult plasticity of serotonergic neurons and their target cells. In: Baumgartner HG, Goethert M, eds. Serotonergic neurons and 5-HT receptors in the CNS. New York; Springer 1997: 1-39
    Google Scholar
  • 4 Boullin D, Freeman B J, Geller E, Ritvo E, Rutter M, Yuwiler A. Toward the resolution of conflicting findings.  J Autism Dev Disord. 1982;  12 97-103
    PubMedGoogle Scholar
  • 5 Bruening G, Liangos O, Baumgartner H G. Prenatal development of the serotonin transporter in mouse brain.  Cell Tissue Res. 1997;  289 211-221
    CrossrefPubMedGoogle Scholar
  • 6 Cook E H, Arora R C, Anderson G M, Berry-Kravis E M, Yan S, Yeoh H C. Platelet serotonin studies in hyperserotonemic relatives of children with autistic disorder.  Life Sci. 1993;  52 20056-20015
    PubMedGoogle Scholar
  • 7 Cook E H, Courchesne R, Lord C, Cox N J, Yan S, Lincoln A. Evidence of linkage between the serotonin transporter and autistic disorder.  Mol Psychiatry. 1997;  2 247-250
    CrossrefPubMedGoogle Scholar
  • 8 Chugani D C, Muzik O, Rothermel R. Altered serotonin synthesis in the dentato-thalamo-cortical pathway in autistic boys.  Ann Neurol. 1997;  42 666-669
    CrossrefPubMedGoogle Scholar
  • 9 Hoffman B J, Mezey E, Brownstein M J. Cloning of a serotonin transporter affected by antidepressants.  Science. 1991;  254 579-580
    PubMedGoogle Scholar
  • 10 Hoshino Y, Yamamoto T, Kaneko M. Blood serotonin and free tryptophan concentration in autistic children.  Neuropsychobiology. 1984;  11 22-27
    PubMedGoogle Scholar
  • 11 Ieni J R, Zukin S R, Van Praag H M. Human platelets possess multiple 3H-imipramine binding sites.  Eur J Pharmacol. 1985;  106 669-672
    PubMedGoogle Scholar
  • 12 Klauch S, Poustka F, Brenner A, Lesch K P, Poustka A. Serotonin transporter (5-HTT) gene variants associated with autism?.  Hum Mol Genet. 1997;  6 2233-2238
    CrossrefPubMedGoogle Scholar
  • 13 Laruelle M, Vanisberg M A, Maloteaux J M. Regional and subcellular localization in human brain of 3H-paroxetine binding, a marker of serotonin uptake sites.  Biol Psychiatry. 1988;  24 299-309
    CrossrefPubMedGoogle Scholar
  • 14 Lauder J M. Neurotransmitters as growth regulatory signals: role of receptors and second messengers.  Trends Neurosci. 1993;  16 233-240
    CrossrefPubMedGoogle Scholar
  • 15 Lesch K P, Wolozin B L, Murphy D L, Riederer A. Primary structure of the human platelet serotonin uptake: identity with the brain serotonin transporter.  J Neurochem. 1993;  60 2319-2322
    CrossrefPubMedGoogle Scholar
  • 16 Lingjaerde O. Serotonin uptake and efflux in blood platelets from untreated and neuroleptic-treated schizophrenics.  Biol Psychiatry. 1983;  18 1345-1356
    PubMedGoogle Scholar
  • 17 Marazziti D, Rossi A, Gemignani A, Giannaccini G, Pfanner C, Milanfranchi A, Presta S, Lucaccini A, Cassano G B. Decreased 3H-paroxetine binding in obsessive-compulsive patients.  Neuropsychobiology. 1996;  4 184-187
    PubMedGoogle Scholar
  • 18 Marazziti D, Rossi A, Giannaccini G, Baroni S, Lucaccini A, Cassano G B. Presence and characterization of the serotonin transporter in human resting lymphocytes.  Neuropsychopharmacology. 1998;  19 154-159
    CrossrefPubMedGoogle Scholar
  • 19 Marcusson J O, Ross S B. Binding of some antidepressants to the 5-hydroxytryptamine transporter in brain and platelets.  Psychopharmacology. 1991;  102 145-155
    PubMedGoogle Scholar
  • 20 McDougle C J, Naylor S T, Cohen C J. Effect of tryptophan depletion in drug-free adults with autistic disorder.  Arch Gen Psychiatry. 1996;  53 993-1000
    PubMedGoogle Scholar
  • 21 McPherson G A. Kinetic, EBDA, LIGAND, Lowry: a collection of radioligand binding analysis programs. Cambridge; Biosoft 1985
    Google Scholar
  • 22 Mellerup E T, Plenge P, Engelstoft M. High-affinity binding of 3H-paroxetine and 3H-imipramine to human platelet membranes.  Eur J Pharmacol. 1983;  96 303-309
    CrossrefPubMedGoogle Scholar
  • 23 Meyerson L R, Ieni J R, Wennogle L P. Allosteric interaction between the site labelled by 3H-imipramine and the serotonin transporter in human platelets.  J Neurochem. 1987;  48 560-565
    PubMedGoogle Scholar
  • 24 Nie N H, Hull C H, Steinbrenner K, Bent D H. Statistical Package for the Social Sciences (SPSS). New York; McGraw-Hill Company 2nd edition 1975
    Google Scholar
  • 25 Peterson G L. A simplification of the protein assay method that is more generally applicable.  Analyt Biochem. 1977;  83 346-356
    CrossrefPubMedGoogle Scholar
  • 26 Potenza M C, Dougle C J. The role of serotonin in autism-spectrum disorders.  CNS Spectrum. 1997;  2 25-42
    PubMedGoogle Scholar
  • 27 Ramamoorthy S, Bauman A L, Moore K R, Han H, Yang-Feng T, Chang A S, Ganapathy V, Blakely R D. Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression and chromosomal Iocalization.  Proc Natl Acad Sci. 1993;  90 2542-2546
    PubMedGoogle Scholar
  • 28 Rausch J J, Hutchinson J, Li X. Correlations of drug action between human platelets and human brain SHT.  Biol Psychiatry. 1995;  137 (suppl) 600
    PubMedGoogle Scholar
  • 29 Schain R J, Freedman D X. Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children.  J Pediatr. 1961;  58 315-320
    CrossrefPubMedGoogle Scholar
  • 30 Schmahmann J J. In: Bauman ML, Kemper TL, eds. The neurobiology of autism. Baltimore; John Hopkins University Press 1994: 195-226
    Google Scholar
  • 31 Sette M, Briley M R, Langer S Z. Complex inhibition of 3H-imipramine binding by serotonin and non-tricyclic serotonin uptake blockers.  J Neurochem. 1983;  40 622-628
    PubMedGoogle Scholar
  • 32 Shopler E, Reichler R J, Rochen Renner B. Western Psychological Service Los Angeles, CA, USA; 1988
  • 33 Singh V KK, Singh E A, Warren R P. Hyperserotonemia and serotonin receptor antibodies in children with autism but not mental retardation.  Biol. Psychiatry. 1997;  41 753-755
    CrossrefPubMedGoogle Scholar
  • 34 Todd R D, Ciaranello R D. Demonstration of inter- and intraspecies differences in serotonin binding sites by antibodies from an autistic child.  Proc Natl Acad Sci USA. 1985;  82 612-616
    PubMedGoogle Scholar
  • 35 Wennogle L P, Meyerson L R. Serotonin uptake inhibitors differentially modulate high affinity imipramine dissociation in human platelet membranes.  Eur J Pharmacol. 1985;  86 303-307
    PubMedGoogle Scholar

MD Donatella Marazziti

Dipartmento di Psichiatria, Neurobiologia

Farmacologia e Biotecnologie University of Pisa

via Roma, 67

56100 Pisa

Italy

Phone: + 39 050/835412

Fax: + 39 050/21581

Email: dmarazzi@psico.med.unipi.it