ArticlePsychopharmacology2012
Tryptophan depletion disinhibits punishment but not reward prediction: implications for resilience.
Article in Psychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Differential Associations of Dopamine and Serotonin With Reward and Punishment Processes in Humans: A Systematic Review and Meta-Analysis.JAMA psychiatry · 2025Pooled it
- The behavioural effects of the serotonin 1A receptor agonist buspirone on reward processing in healthy volunteers: A randomised, placebo-controlled study.Journal of psychopharmacology (Oxford, England) · 2026Trial
- Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans.Molecular psychiatry · 2021Trial
- Cortico-limbic connectivity in MAOA-L carriers is vulnerable to acute tryptophan depletion.Human brain mapping · 2017Trial
- Beyond negative valence: 2-week administration of a serotonergic antidepressant enhances both reward and effort learning signals.PLoS biology · 2017Trial
- Serotonin reuptake inhibitors and serotonin transporter genotype modulate performance monitoring functions but not their electrophysiological correlates.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Trial
- Trial
- Acute tryptophan depletion increases translational indices of anxiety but not fear: serotonergic modulation of the bed nucleus of the stria terminalis?Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Trial
- The influence of serotonin on fear learning.PloS one · 2012Trial
- Brain serotonin transporter is associated with cognitive-affective biases in healthy individuals.Human brain mapping · 2022Article
- Article
- Article
- Review
- Effects of SSRI Antidepressants on Attentional Bias toward Emotional Scenes in First-Episode Depressive Patients: Evidence from an Eye-Tracking Study.Psychiatry investigation · 2020Article
- The Role of Tryptophan and Tyrosine in Executive Function and Reward Processing.International journal of tryptophan research : IJTR · 2020Review
- Dissociable Effects of Tryptophan Supplementation on Negative Feedback Sensitivity and Reversal Learning.Frontiers in behavioral neuroscience · 2019Article
- The role of prefrontal-subcortical circuitry in negative bias in anxiety: Translational, developmental and treatment perspectives.Brain and neuroscience advances · 2018Article
- The Neural Mechanism Underlying Cognitive and Emotional Processes in Creativity.Frontiers in psychology · 2018Review
- 5-HT modulation of pain perception in humans.Psychopharmacology · 2017Article
- Toward a multiscale modeling framework for understanding serotonergic function.Journal of psychopharmacology (Oxford, England) · 2017Review
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3 authors at 3 institutions in 2 countries.
Funding
Abstract
rationaleWe have previously shown that tryptophan depletion enhances punishment but not reward prediction (Cools et al. in Neuropsychopharmacology 33:2291-2299, 2008b). This provided evidence for a valence-specific role of serotonin (which declines under depleted tryptophan) in aversive processing. Recent theoretical (Dayan and Huys in PLoS Comput Biol 4:e4, 2008) and experimental (Crockett et al. in J Neurosci 29:11993-11999, 2009) approaches have, however, further specified this role by showing that serotonin is critical for punishment-induced inhibition.
objectivesWe sought to examine the role of serotonin in punishment-induced inhibition. We also examined the impact of induced mood on this effect to assess whether effects of tryptophan depletion on affective inhibition are moderated by mood.
methodsHealthy females consumed a balanced amino acid mixture with (N = 20) or without (N = 21) the serotonin precursor tryptophan. Each subject completed either negative or neutral mood induction. All subjects completed the reward and punishment reversal learning task adopted in the previous study.
resultsWe demonstrate a punishment prediction impairment in individuals who consumed tryptophan which was absent in individuals who were depleted of tryptophan. This effect was impervious to mood state.
conclusionsOur results suggest that serotonin promotes the inhibition of responses to punishing outcomes. This may lead to reduced punishment prediction accuracy in the presence of tryptophan and may contribute to resilience to affective disorders. Reduction of serotonin via tryptophan depletion then removes this inhibition. As such, we highlight a mechanism by which reduced serotonin can contribute to disorders of impulsivity and compulsivity as well as disorders of emotion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.