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

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 +4 more·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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  • The stronger dependence on serotonin in at-risk subjects would explain why only they are sensitive to the mood effects of tryptophan depletion, and why individuals with a polymorphism in the serotonin transporter gene that reduces serotonin uptake are more liable to develop mood disturbance, especially following serotonin depletion.

    “The stronger dependence on serotonin in at-risk subjects would explain why only they are sensitive to the mood effects of tryptophan depletion [34], and why individuals with a polymorphism in the serotonin transporter gene that reduces serotonin uptake are more liable to develop mood disturbance, especially following serotonin depletion [41], [42].”

    From Bonsai trees in your head: how the pavlovian system sculpts goal-directed choices by pruning decision trees (2012) · cites this paper as [42]

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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
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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