This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Mössner, R. Articles by Walitza, S. Search for Related Content PubMed PubMed Citation Articles by Mössner, R. Articles by Walitza, S. Social Bookmarking                         What's this?

Transmission disequilibrium analysis of the functional 5-HT_3A receptor variant C178T in early-onset obsessive—compulsive disorder

Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany, rainald.mossner{at}mail.uni-wurzberg.de

Nicole Döring

Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany

André Scherag

Institute for Medical Biometry and Epidemiology, Philipps-University Marburg, Marburg, Germany

Helmut Schäfer

Institute for Medical Biometry and Epidemiology, Philipps-University Marburg, Marburg, Germany

Beate Herpertz-Dahlmann

Department of Child and Adolescent Psychiatry, Technical University of Aachen, Aachen, Germany

Helmut Remschmidt

Clinical Research Group, Department of Child and Adolescent Psychiatry, Philipps-University Marburg, Marburg, Germany

Eberhard Schulz

Department of Child and Adolescent Psychiatry, University of Freiburg, Freiburg, Germany

Tobias Renner

Department of Child and Adolescent Psychiatry, University of Würzburg, Würzburg, Germany

Christoph Wewetzer

Department of Child and Adolescent Psychiatry, University of Würzburg, Würzburg, Germany

Andreas Warnke

Department of Child and Adolescent Psychiatry, University of Würzburg, Würzburg, Germany

Klaus-Peter Lesch

Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany

Susanne Walitza

Department of Child and Adolescent Psychiatry, University of Würzburg, Würzburg, Germany

The 5-HT₃ receptor is unique among the serotonin receptors in that it is a ligand-gated ion channel. Dysfunction of the serotonin system is thought to contribute to the pathogenesis of obsessive—compulsive disorder (OCD). Apart from the standard treatment with serotonin reuptake inhibitors and behavioural therapy, a 5-HT₃ receptor antagonist has recently been shown to benefit some OCD patients, suggesting the 5-HT₃ receptor as a serotonergic candidate gene in the polygenic aetiology of OCD. A functional regulatory variant of the 5-HT_3A receptor influences 5-HT ₃ receptor expression, serotonin metabolites in cerebrospinal fluid, and amygdala reactivity. We therefore assessed whether this C178T variant influences the risk of developing OCD. In a family-based approach employing the transmission disequilibrium test, we analysed a unique sample of 75 children and adolescents with OCD, as well as their biological parents. We found no evidence for a preferential transmission of either allele to the patients — the estimated transmission rate for the C allele was 0.51 (95% CI 0.36—0.65). This argues against an involvement of the 5-HT_3A receptor in the polygenic aetiology of early-onset OCD.

Key Words: OCD • serotonin • HTR3A

References

• Andrews G., Stewart G., Allen R., Henderson A.S. (1990) The genetics of six neurotic disorders: a twin study . J Affect Disord 19: 23—29 [CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Apa (2000) DSM-IV: diagnostic and statistical manual of mental disorders. American Psychiatric Association, Washington, DC
• Arnold P.D., Richter M.A. (2001) Is obsessive—compulsive disorder an autoimmune disease? Cmaj 165: 1353—1358 [Abstract/Free Full Text]
• Baumgarten H.G., Grozdanovic Z. (1998) Role of serotonin in obsessive—compulsive disorder . Br J Psychiatry (35) (suppl.): 13—20
• Brandes M., Soares C.N., Cohen L.S. (2004) Postpartum onset obsessive—compulsive disorder: diagnosis and management. Arch Womens Ment Health 7: 99—110
• Casella G. (1986) Refining binomial confidence intervals . Canadian Journal of Statistics 14: 113—129 [CrossRef]
• Chabane N., Delorme R., Millet B., Mouren M.C., Leboyer M., Pauls D. (2005) Early-onset obsessive—compulsive disorder: a subgroup with a specific clinical and familial pattern? J Child Psychol Psychiatry 46: 881—887 [CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Costall B., Naylor R.J., Tyers M.B. (1990) The psychopharmacology of 5-HT3 receptors . Pharmacol Ther 47: 181—202 [CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Eisensamer B., Rammes G., Gimpl G., Shapa M., Ferrari U., Hapfelmeier G., Bondy B., Parsons C., Gilling K., Zieglgänsberger W., Holsboer F., Rupprecht R. (2003) Antidepressants are functional antagonists at the serotonin type 3 (5-HT3) receptor. Molecular Psychiatry 8: 994—1007
• Fan P. ( 1994) Inhibition of a 5-HT3 receptor-mediated current by the selective serotonin uptake inhibitor, fluoxetine . Neuroscience Letters 173: 210—212 [CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Fineberg N.A., Gale T.M. (2005) Evidence-based pharmacotherapy of obsessive—compulsive disorder . Int J Neuropsychopharmacol 8: 107—129 [CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Goodman W.K., Price L.H., Rasmussen S.A., Mazure C., Delgado P., Heninger G.R., Charney D.S. (1989) The Yale-Brown Obsessive Compulsive Scale. II. Validity . Arch Gen Psychiatry 46: 1012—1016 [Abstract/Free Full Text]
• Hewlett W.A., Schmid S.P., Salomon R.M. (2003) Pilot trial of ondansetron in the treatment of 8 patients with obsessive—compulsive disorder. Journal of Clinical Psychiatry 64: 1025—1030
• Hoekstra P.J., Minderaa R.B. (2005) Tic disorders and obsessive—compulsive disorder: is autoimmunity involved? Int Rev Psychiatry 17: 497—502 [CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Iidaka T., Ozaki N., Matsumoto A., Nogawa J., Kinoshita Y., Suzuki T., Iwata N., Yamamoto Y., Okada T., Sadato N. (2005) A variant C178T in the regulatory region of the serotonin receptor gene HTR3A modulates neural activation in the human amygdala . Journal of Neuroscience 25: 6460—6466 [Abstract/Free Full Text]
• Jönsson E.G., Bah J., Melke J., Jamra R.A., Schumacher J., Westberg L., Ivo R., Cichon S., Propping P., Nöthen M.M., Eriksson E., Sedvall G.C. (2004) Monoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers . BMC Psychiatry 4: 4 [CrossRef][Medline] [Order article via Infotrieve]
• Kilpatrick G.J., Jones B.J., Tyers M.B. (1987) Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding . Nature 330: 746—748 [CrossRef][Medline] [Order article via Infotrieve]
• Mössner R., Schmitt A., Hennig T., Benninghoff J., Gerlach P., Riederer P., Deckert J., Lesch K P. (2004) Quantitation of 5HT3 receptors in forebrain of serotonin transporter deficient mice . Journal of Neural Transmission 111: 27—35 [CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Nestadt G., Samuels J., Riddle M., Bienvenu O.J., Liang K.Y., LaBuda M., Walkup J., Grados M., Hoehn-Saric R. (2000) A family study of obsessive—compulsive disorder . Arch Gen Psychiatry 57: 358—363 [Abstract/Free Full Text]
• Niesler B., Flohr T., Nöthen M M., Fischer C., Rietschel M., Franzek E., Albus M., Propping P., Rappold G A. (2001) Association between the 5'UTR variant C178T of the serotonin receptor gene HTR3A and bipolar affective disorder . Pharmacogenetics 11: 471—475 [CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Pauls D L., Alsobrook J P II, Goodman W., Rasmussen S., Leckman J F. (1995) A family study of obsessive-compulsive disorder . Am J Psychiatry 152: 76—84 [Abstract/Free Full Text]
• Spielman R S., McGinnis R E., Ewens W J. (1993) Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM) . Am J Hum Genet 52: 506—516 [Web of Science][Medline] [Order article via Infotrieve]
• Torgersen S. (1990) Comorbidity of major depression and anxiety disorders in twin pairs . Am J Psychiatry 147: 1199—1202 [Abstract/Free Full Text]
• Unnewehr S. (1995) [Diagnosis of psychiatric disorders in children and adolescents using structured interviews] . Z Kinder Jugendpsychiatr 23: 121—132 [Web of Science][Medline] [Order article via Infotrieve]
• Who (1993) The ICD-10 classification of mental and behavioural disorders, World Health Organization: Geneva
• Zohar J., Chopra M., Sasson Y., Amiaz R., Amital D. (2000) Obsessive compulsive disorder: serotonin and beyond. World J Biol Psychiatry 1: 92—100 [Medline] [Order article via Infotrieve]

This version was published on November 1, 2007

Journal of Psychopharmacology, Vol. 21, No. 8, 833-836 (2007)
DOI: 10.1177/0269881106073560


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Mössner, R. Articles by Walitza, S. Search for Related Content PubMed PubMed Citation Articles by Mössner, R. Articles by Walitza, S. Social Bookmarking                         What's this?