Serotonin transporter genetic variation and the response of the human amygdala

Ahmad R. Hariri, Venkata Mattay, Alessandro Tessitore, Bhaskar Kolachana, Francesco Fera, David Goldman, Michael F. Egan, Daniel Weinberger

Research output: Contribution to journalArticle

Abstract

A functional polymorphism in the promoter region of the human serotonin transporter gene (SLC6A4) has been associated with several dimensions of neuroticism and psychopathology, especially anxiety traits, but the predictive value of this genotype against these complex behaviors has been inconsistent. Serotonin [5-hydroxytryptamine, (5-HT)] function influences normal fear as well as pathological anxiety, behaviors critically dependent on the amygdala in animal models and in clinical studies. We now report that individuals with one or two copies of the short allele of the serotonin transporter (5-HTT) promoter polymorphism, which has been associated with reduced 5-HTT expression and function and increased fear and anxiety-related behaviors, exhibit greater amygdala neuronal activity, as assessed by BOLD functional magnetic resonance imaging, in response to fearful stimuli compared with individuals homozygous for the long allele. These results demonstrate genetically driven variation in the response of brain regions underlying human emotional behavior and suggest that differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.

Original languageEnglish (US)
Pages (from-to)400-403
Number of pages4
JournalScience
Volume297
Issue number5580
DOIs
StatePublished - Jul 19 2002
Externally publishedYes

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Serotonin Plasma Membrane Transport Proteins
Amygdala
Anxiety
Fear
Alleles
Serotonin
Psychopathology
Genetic Promoter Regions
Animal Models
Genotype
Magnetic Resonance Imaging
Brain
Genes

ASJC Scopus subject areas

  • General

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Serotonin transporter genetic variation and the response of the human amygdala. / Hariri, Ahmad R.; Mattay, Venkata; Tessitore, Alessandro; Kolachana, Bhaskar; Fera, Francesco; Goldman, David; Egan, Michael F.; Weinberger, Daniel.

In: Science, Vol. 297, No. 5580, 19.07.2002, p. 400-403.

Research output: Contribution to journalArticle

Hariri, AR, Mattay, V, Tessitore, A, Kolachana, B, Fera, F, Goldman, D, Egan, MF & Weinberger, D 2002, 'Serotonin transporter genetic variation and the response of the human amygdala', Science, vol. 297, no. 5580, pp. 400-403. https://doi.org/10.1126/science.1071829
Hariri AR, Mattay V, Tessitore A, Kolachana B, Fera F, Goldman D et al. Serotonin transporter genetic variation and the response of the human amygdala. Science. 2002 Jul 19;297(5580):400-403. https://doi.org/10.1126/science.1071829
Hariri, Ahmad R. ; Mattay, Venkata ; Tessitore, Alessandro ; Kolachana, Bhaskar ; Fera, Francesco ; Goldman, David ; Egan, Michael F. ; Weinberger, Daniel. / Serotonin transporter genetic variation and the response of the human amygdala. In: Science. 2002 ; Vol. 297, No. 5580. pp. 400-403.
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