Serotonin transporter polymorphism mediates vulnerability to loss of incentive motivation following acute tryptophan depletion.
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The serotonin (5-HT) system is implicated in incentive motivational processes. The present study utilized the acute tryptophan depletion (ATD) procedure to investigate the effect of temporarily lowering 5-HT synthesis on motivation in healthy volunteers, stratifying the results by allelic variation at the serotonin transporter gene (5-HTTLPR). ATD resulted in a robust reduction in plasma tryptophan concentration. Consistent with a previous study, ATD attenuated motivationally speeded action on the Cued-Reinforcement Reaction Time task. The present investigation revealed that this effect was restricted to volunteers of the ss genotype, whereas ll volunteers exhibited intact motivationally speeded action following ATD (treatment x reinforcement probability x genotype interaction: F1,26=5.8, p=0.024). Furthermore, tryptophan availability to the brain was correlated positively with motivationally speeded action following ATD in the ss genotype group (rho13=0.71, p=0.006), whereas this correlation was negative in the ll genotype group (rho14=-0.60, p=0.023). This is the first study to suggest that allelic variation at the 5-HTTLPR mediates motivational responses to ATD in healthy volunteers. These data indicate that the s allele at the 5-HTTLPR may confer risk for depression via its effect on incentive motivational processing, and highlight the importance of genetic variation in determining individual responses to pharmacological treatments.
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Dayan and Huys [17] explained the serotonin-depression paradox by suggesting that people who experienced high levels of serotonin and exaggerated Pavlovian behavioural inhibition during early development would be most sensitive to effects of any interference with this inhibition in adulthood secondary to a drop in serotonin levels.
“Dayan and Huys [17] explained this paradox by suggesting that people who experienced high levels of serotonin and thus exaggerated Pavlovian behavioural inhibition during early development [32] would be most sensitive to the effects of any interference with this inhibition in adulthood secondary to a drop in serotonin levels [33], [34].”
From Bonsai trees in your head: how the pavlovian system sculpts goal-directed choices by pruning decision trees (2012) · cites this paper as [33]
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- Authors
- Roiser, J. P., Blackwell, A. D., Cools, R., Clark, L., Rubinsztein, D. C., Robbins, T. W., & Sahakian, B. J.
- Affiliations
- Addenbrooke's Hospital (GB)
- University of Cambridge (GB)
- Corresponding author
- Roiser, Jonathan P
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2006-03-15
- Volume
- 31
- Issue
- 10
- Pages
- 2264-2272
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC1852058
- OpenAlex
- W1968378085
- Cited by
- 98
- References
- 64
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 4 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 6 · 2014: 10 · 2013: 3 · 2012: 7
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Update notices
- erratum (2006-09-18)
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (076244/Z/04/Z, 019407)
- University of Oxford
- Universiteit Utrecht
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- serotonin transporter gene, 5-HTTLPR, acute tryptophan depletion, incentive motivation, reward processing, S-alleles, depression risk, genetic polymorphism, individual differences in treatment response
- MeSH terms
- Adult, Analysis of Variance, Cues, Double-Blind Method, Female, Genotype, Humans, Male, Motivation, Polymorphism, Genetic, Probability, Reaction Time, Reinforcement, Psychology, Statistics as Topic, Tryptophan, Diet, Protein-Restricted, Serotonin Plasma Membrane Transport Proteins
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