Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012
Acute tryptophan depletion increases translational indices of anxiety but not fear: serotonergic modulation of the bed nucleus of the stria terminalis?
Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Effects of tryptophan depletion on anxiety, a systematic review.Translational psychiatry · 2021Pooled it
- Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans.Molecular psychiatry · 2021Trial
- The novel vasopressin receptor (V1aR) antagonist SRX246 reduces anxiety in an experimental model in humans: a randomized proof-of-concept study.Psychopharmacology · 2021Trial
- Effect of Tryptophan Depletion on Conditioned Threat Memory Expression: Role of Intolerance of Uncertainty.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2021Trial
- Trial
- The Role of Serotonin in Fear Learning and Memory: A Systematic Review of Human Studies.Brain sciences · 2023Review
- Demonstrating a link between diet, gut microbiota and brain:Frontiers in nutrition · 2023Article
- Gut Biofactory-Neurocompetent Metabolites within the Gastrointestinal Tract. A Scoping Review.Nutrients · 2020Article
- Altered learning under uncertainty in unmedicated mood and anxiety disorders.Nature human behaviour · 2019Article
- The anxiolytic-like effects of puerarin are associated with the changes of monoaminergic neurotransmitters and biosynthesis of allopregnanolone in the brain.Metabolic brain disease · 2018Article
- Role of the bed nucleus of the stria terminalis in aversive learning and memory.Learning & memory (Cold Spring Harbor, N.Y.) · 2017Review
- Reducing State Anxiety Using Working Memory Maintenance.Journal of visualized experiments : JoVE · 2017Article
- Probing for Neuroadaptations to Unpredictable Stressors in Addiction: Translational Methods and Emerging Evidence.Journal of studies on alcohol and drugs · 2017Review
- Using a cultural and RDoC framework to conceptualize anxiety in Asian Americans.Journal of anxiety disorders · 2017Article
- Anxiety Patients Show Reduced Working Memory Related dlPFC Activation During Safety and Threat.Depression and anxiety · 2017Article
- Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders.Molecular psychiatry · 2016Review
- Stress Modulation of Opposing Circuits in the Bed Nucleus of the Stria Terminalis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Review
- The Human BNST: Functional Role in Anxiety and Addiction.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Review
- The impact of stress on financial decision-making varies as a function of depression and anxiety symptoms.PeerJ · 2015Article
- Exaggerated neurobiological sensitivity to threat as a mechanism linking anxiety with increased risk for diseases of aging.Neuroscience and biobehavioral reviews · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Serotonin is strongly implicated in the mammalian stress response, but surprisingly little is known about its mode of action. Recent data suggest that serotonin can inhibit aversive responding in humans, but this remains underspecified. In particular, data in rodents suggest that global serotonin depletion may specifically increase long-duration bed nucleus of the stria terminalis (BNST)-mediated aversive responses (ie, anxiety), but not short-duration BNST-independent responses (ie, fear). Here, we extend these findings to humans. In a balanced, placebo-controlled crossover design, healthy volunteers (n=20) received a controlled diet with and without the serotonin precursor tryptophan (acute tryptophan depletion; ATD). Aversive states were indexed by translational acoustic startle measures. Fear and anxiety were operationally defined as the increase in startle reactivity during short- and long-duration threat periods evoked by predictable shock (fear-potentiated startle) and by the context in which the shocks were administered (anxiety-potentiated startle), respectively. ATD significantly increased long-duration anxiety-potentiated startle but had no effect on short-duration fear-potentiated startle. These results suggest that serotonin depletion in humans selectively increases anxiety but not fear. Current translational frameworks support the proposition that ATD thus disinhibits dorsal raphé-originating serotonergic control of corticotropin-releasing hormone-mediated excitation of the BNST. This generates a candidate neuropharmacological mechanism by which depleted serotonin may increase response to sustained threats, alongside clear implications for our understanding of the manifestation and treatment of mood and anxiety disorders.
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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.