Cited by 223Neurotransmitter Receptor Influence on BehaviorTryptophan and brain disordersGenetic Associations and Epidemiology

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Association between serotonin transporter gene promoter polymorphism (5HTTLPR) and behavioral responses to tryptophan depletion in healthy women with and without family history of depression.

Neumeister, Alexander, Konstantinidis, Anastasios, Stastny, Juergen, Schwarz, Markus J., Vitouch, Oliver, Willeit, Matthaus, Praschak-Rieder, Nicole, Zach, Johanna, de Zwaan, Martina, Bondy, Brigitta, Ackenheil, Manfred, Kasper, Siegfried·2002·Archives of General Psychiatry

DOI 10.1001/archpsyc.59.7.613

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Abstract

BACKGROUND: Evidence suggests that serotonin transporter gene promoter polymorphism (5HTTLPR)-dependent low transcriptional activity of the human serotonin transporter gene may be a genetic susceptibility factor for depression. We studied the behavioral responses to tryptophan depletion (TD) in healthy women with and without a first-degree family history of depression and examined the relationship to 5HTTLPR alleles. METHODS: Twenty-four healthy women with a negative family history of depression and 21 women with a positive family history of depression were genotyped for the polymorphism of the 5HTTLPR and then entered a double-blind, placebo-controlled, randomized crossover TD study. The effects of these interventions were assessed with measures of depression and plasma tryptophan levels. RESULTS: The TD induced a robust decrease of plasma tryptophan levels in all women irrespective of family history of depression or 5HTTLPR genotypes. The s/s genotype of the 5HTTLPR was associated with an increased risk of developing depressive symptoms during TD irrespective of family history. In contrast, individuals with the l/l genotype did not develop depressive symptoms, irrespective of family history. Finally, s/l subjects without family history showed a mood response that was intermediate between the s/s and l/l subjects, while s/l subjects with a family history of depression showed the same depressiogenic effect of TD as seen in the s/s subjects. CONCLUSIONS: The results of the present study suggest that the s-allele of the 5HTTLPR and a positive family history of depression are additive risk factors for the development of depression during TD.

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Authors: Neumeister, A., Konstantinidis, A., Stastny, J., Schwarz, M. J., Vitouch, O., Willeit, M., Praschak-Rieder, N., Zach, J., de Zwaan, M., Bondy, B., Ackenheil, M., & Kasper, S.
Affiliations: National Institutes of Health (US)
Max Planck Society (DE)
ORCID: Schwarz, Markus J.
Vitouch, Oliver
Praschak-Rieder, Nicole
Kasper, Siegfried
Venue: Archives of General Psychiatry
Publisher: American Medical Association (AMA)
Published: 2002-07-01
Volume: 59
Issue: 7
Pages: 613
ISSN: 0003-990X (ISSN-L)
DOI: 10.1001/archpsyc.59.7.613
OpenAlex: W2111173241
Cited by: 223
References: 78
Citations by year: 2026: 3 · 2024: 1 · 2023: 6 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 3 · 2013: 8 · 2012: 10
FWCI: 6.28
Type: journal article
Language: en
Open access: closed
Locations: Archives of General Psychiatry (publishedVersion)
PubMed (publishedVersion)
Max Planck Institute for Plasma Physics (submittedVersion)
MPG.PuRe (Max Planck Society) (submittedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: 5-HTTLPR, serotonin transporter gene, tryptophan depletion, family history of depression, genetic susceptibility to depression, S-alleles, depressive symptoms, women, gene-environment interaction
MeSH terms: Adult, Carrier Proteins, Depressive Disorder, Family, Female, Genotype, Humans, Membrane Glycoproteins, Nerve Tissue Proteins, Placebos, Polymorphism, Genetic, Promoter Regions, Genetic, Risk Factors, Serotonin, Tryptophan, Genetic Predisposition to Disease, Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins

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Association between serotonin transporter gene promoter polymorphism (5HTTLPR) and behavioral responses to tryptophan depletion in healthy women with and without family history of depression.

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