Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects
Open accessAbstract
The acute tryptophan depletion (ATD) technique has been used extensively to study the effect of low serotonin in the human brain. This review assesses the validity of a number of published criticisms of the technique and a number of previously unpublished potential criticisms. The conclusion is that ATD can provide useful information when results are assessed in conjunction with results obtained using other techniques. The best-established conclusion is that low serotonin function after tryptophan depletion lowers mood in some people. However, this does not mean that other variables, altered after tryptophan depletion, are necessarily related to low serotonin. Each aspect of brain function has to be assessed separately. Furthermore, a negative tryptophan depletion study does not mean that low serotonin cannot influence the variable studied. This review suggests gaps in knowledge that need to be filled and guidelines for carrying out ATD studies.
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The inhibitory actions of acute escitalopram on terminal 5-HT release, through actions at auto-receptors on raphé 5-HT neurons, may be analogous to the presumed transient reduction in 5-HT activity caused by ATD.
“The inhibitory actions of acute escitalopram administration on terminal 5-HT release, through actions at auto-receptors on raphé 5-HT neurons [8], may be analogous to the presumed transient reduction in 5-HT activity caused by ATD [49].”
From Dissociable effects of acute SSRI (escitalopram) on executive, learning and emotional functions in healthy humans (2018) · cites this paper as [49]
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“However, the effect of ATD on mood depends on the characteristics of the individuals being studied, with effects ranging from nothing, to a dramatic lowering of mood in newly discovered depressed patients who are treated with serotonergic antidepressants.(25) The lack of mood lowering could be due to adaptive processe…”
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“The main insight into the variable mood response after ATD is in the study of Yatham and colleagues.(28) In recovered depressed patients who showed no lowering of mood after ATD, there was an ATD-induced reduction of serotonin 2 receptors.”
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- Authors
- Young, S. N.
- Affiliations
- McGill University (CA)
- Corresponding author
- Young, Simon N.
- ORCID
- Young, Simon N.
- Venue
- Journal of Psychiatry and Neuroscience
- Publisher
- Canadian Science Publishing
- Published
- 2013-09
- Volume
- 38
- Issue
- 5
- Pages
- 294-305
- ISSN
- 1180-4882 (ISSN-L)
- 1488-2434
- PMC
- PMC3756112
- OpenAlex
- W2098120777
- Cited by
- 110
- References
- 9
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 5 · 2023: 13 · 2022: 15 · 2021: 8 · 2020: 8 · 2019: 7 · 2018: 11 · 2017: 10 · 2016: 8 · 2015: 5 · 2014: 3 · 2013: 3
- FWCI
- 0.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Psychiatry and Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- acute tryptophan depletion, serotonin, mood, methodological validity, research ethics, negative results, brain function
- MeSH terms
- Affect, Animals, Brain, Food, Formulated, Humans, Serotonin, Tryptophan, Bioethical Issues
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