Trial reportMolecular psychiatry2021
Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans.
Trial report in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07507266 (Evaluation of Emotions From Salivary Molecular Biomarkers in an Architectural Context), which is not on this map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Evaluation of Emotions From Salivary Molecular Biomarkers in an Architectural Context
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 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
- Computational modelling and neural correlates of reinforcement learning following three-week escitalopram: a double-blind, placebo-controlled semi-randomised study.Translational psychiatry · 2025Trial
- Chronic escitalopram in healthy volunteers has specific effects on reinforcement sensitivity: a double-blind, placebo-controlled semi-randomised study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- Revisiting the Role of Serotonin in Attention-Deficit Hyperactivity Disorder: New Insights from Preclinical and Clinical Studies.Clinical drug investigation · 2025Review
- Monoaminergic Modulation of Learning and Cognitive Function in the Prefrontal Cortex.Brain sciences · 2024Review
- Direct serotonin release in humans shapes aversive learning and inhibition.Nature communications · 2024Article
- 5-HT 2A and 5-HT 2C receptor antagonism differentially modulate reinforcement learning and cognitive flexibility: behavioural and computational evidence.Psychopharmacology · 2024Article
- Ketamine produces no detectable long-term positive or negative effects on cognitive flexibility or reinforcement learning of male rats.Psychopharmacology · 2024Article
- Delay of punishment highlights differential vulnerability to developing addiction-like behavior toward sweet food.Translational psychiatry · 2024Article
- Comparable roles for serotonin in rats and humans for computations underlying flexible decision-making.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Perseveration and Shifting in Obsessive-Compulsive Disorder as a Function of Uncertainty, Punishment, and Serotonergic Medication.Biological psychiatry global open science · 2024Article
- Prefrontal serotonin depletion delays reversal learning and increases theta synchronization of the infralimbic-prelimbic-orbitofrontal prefrontal cortex circuit.Frontiers in pharmacology · 2024Article
- Serotonin and emotion regulation: the impact of tryptophan depletion on emotional experience, neural and autonomic activity.Cognitive, affective & behavioral neuroscience · 2023Article
- Dorsal raphe neurons signal integrated value during multi-attribute decision-making.bioRxiv : the preprint server for biology · 2023Article
- A neurobiological perspective on social influence: Serotonin and social adaptation.Journal of neurochemistry · 2022Review
- Threat reversal learning and avoidance habits in generalised anxiety disorder.Translational psychiatry · 2022Article
- What Can Reinforcement Learning Models of Dopamine and Serotonin Tell Us about the Action of Antidepressants?Computational psychiatry (Cambridge, Mass.) · 2022Review
- A Role for Serotonin in Modulating Opposing Drive and Brake Circuits of Impulsivity.Frontiers in behavioral neuroscience · 2022Review
- Psychedelics, Sociality, and Human Evolution.Frontiers in psychology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 4 countries.
Funding
Abstract
Serotonin is involved in updating responses to changing environmental circumstances. Optimising behaviour to maximise reward and minimise punishment may require shifting strategies upon encountering new situations. Likewise, autonomic responses to threats are critical for survival yet must be modified as danger shifts from one source to another. Whilst numerous psychiatric disorders are characterised by behavioural and autonomic inflexibility, few studies have examined the contribution of serotonin in humans. We modelled both processes, respectively, in two independent experiments (N = 97). Experiment 1 assessed instrumental (stimulus-response-outcome) reversal learning whereby individuals learned through trial and error which action was most optimal for obtaining reward or avoiding punishment initially, and the contingencies subsequently reversed serially. Experiment 2 examined Pavlovian (stimulus-outcome) reversal learning assessed by the skin conductance response: one innately threatening stimulus predicted receipt of an uncomfortable electric shock and another did not; these contingencies swapped in a reversal phase. Upon depleting the serotonin precursor tryptophan-in a double-blind randomised placebo-controlled design-healthy volunteers showed impairments in updating both actions and autonomic responses to reflect changing contingencies. Reversal deficits in each domain, furthermore, were correlated with the extent of tryptophan depletion. Initial Pavlovian conditioning, moreover, which involved innately threatening stimuli, was potentiated by depletion. These results translate findings in experimental animals to humans and have implications for the neurochemical basis of cognitive inflexibility.
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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.