Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.

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Volume 274 | Issue 5292
29 November 1996

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Received: 13 June 1996
Accepted: 22 October 1996
Published in print: 29 November 1996


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Klaus-Peter Lesch*
K.-P. Lesch, A. Heils, S. Petri, Department of Psychiatry, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany.
Dietmar Bengel
D. Bengel, B. D. Greenberg, J. Benjamin, D. L. Murphy, Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Armin Heils
K.-P. Lesch, A. Heils, S. Petri, Department of Psychiatry, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany.
Sue Z. Sabol
S. Z. Sabol and D. H. Hamer, Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Benjamin D. Greenberg
D. Bengel, B. D. Greenberg, J. Benjamin, D. L. Murphy, Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Susanne Petri
K.-P. Lesch, A. Heils, S. Petri, Department of Psychiatry, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany.
Jonathan Benjamin
D. Bengel, B. D. Greenberg, J. Benjamin, D. L. Murphy, Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Clemens R. Müller
C. R. Müller, Institute of Human Genetics, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Dean H. Hamer
S. Z. Sabol and D. H. Hamer, Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Dennis L. Murphy
D. Bengel, B. D. Greenberg, J. Benjamin, D. L. Murphy, Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.


* To whom correspondence should be addressed. E-mail: [email protected]

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