Cited by 396Neurotransmitter Receptor Influence on BehaviorTryptophan and brain disordersStress Responses and Cortisol

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The role of serotonin in human mood and social interaction

Young, Simon N., Leyton, Marco·2002·Pharmacology Biochemistry and Behavior

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Abstract

Alterations in brain tryptophan levels cause changes in brain serotonin synthesis, and this has been used to study the implication of altered serotonin levels in humans. In the acute tryptophan depletion (ATD) technique, subjects ingest a mixture of amino acids devoid of tryptophan. This results in a transient decline in tissue tryptophan and in brain serotonin. ATD can result in lower mood and increase in irritability or aggressive responding. The magnitude of the effect varies greatly depending on the susceptibility of the subject to lowered mood or aggressivity. Unlike ATD, tryptophan can be given chronically. Tryptophan is an antidepressant in mild to moderate depression and a small body of data suggests that it can also decrease aggression. Preliminary data indicate that tryptophan also increases dominant behavior during social interactions. Overall, studies manipulating tryptophan levels support the idea that low serotonin can predispose subjects to mood and impulse control disorders. Higher levels of serotonin may help to promote more constructive social interactions by decreasing aggression and increasing dominance.

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“1899 anxiety, and pain (Young and Leyton, 2002).”
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Sensitive and Selective Measurement of Serotonin in Vivo Using Fast Cyclic Square-Wave Voltammetry
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Nutritional concerns and possible countermeasures to nutritional issues related to space flight
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Fatigue and Depression in Cancer Patients Undergoing Chemotherapy: An Emotion Approach
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St. John's wort (Hypericum perforatum) counteracts cytokine-induced tryptophan catabolism in vitro
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Truncated Electrochemical Aptasensor with Enhanced Antifouling Capability for Highly Sensitive Serotonin Detection
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The c.1460C>T Polymorphism ofMAO-AIs Associated with the Risk of Depression in Postmenopausal Women
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“The central serotoninergic system has been implicated in the pathophysiology of a number of neuropsychiatric disorders such as mood disorders, substance abuse, or alcoholism [1, 2].”
Effects of rapid tryptophan depletion on mood and urge to drink in patients with co-morbid major depression and alcohol dependence
Pierucci‐Lagha, A., Feinn, R., Modesto‐Lowe, V., Swift, R. M., Nellissery, M. J., Covault, J., & Kranzler, H. R. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1588-6 · Cited by 25
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Aqueous Extract of Echium amoenum Elevate CSF Serotonin and Dopamine Level in Depression rat
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Fluoxetine-induced changes in body weight and 5-HT1Areceptor-mediated hormone secretion in rats on a tryptophan-deficient diet
D’Souza, D. N., Zhang, Y., García, F., Battaglia, G., & de Kar, L. D. V. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00335.2003 · Cited by 24
“Additionally, tryptophan-deficient diets and tryptophan-depleting drinks have been tested in humans and were found to produce changes in sleep and mood, including a short-term reversal of the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) (2, 8, 17, 46, 58, 77).”
Background
Cortico‐limbic connectivity in MAOA‐L carriers is vulnerable to acute tryptophan depletion
Eisner, P. D., Klasen, M., Wolf, D., Zerres, K., Eggermann, T., Eisert, A., Zvyagintsev, M., Sarkheil, P., Mathiak, K. A., Zepf, F. D., et al. (2016) · Human Brain Mapping · doi:10.1002/hbm.23475 · Cited by 25
“Apparently, mood decreased in healthy men after ATD [Young and Leyton, 2002]; although, recent research suggests only small, if any, effects of the ATD challenge on the mood in healthy men [Young, 2013].”
Background
Associations among central nervous system serotonergic function and neuroticism are moderated by gender
Brummett, B. H., Boyle, S. H., Kuhn, C. M., Siegler, I. C., & Williams, R. B. (2008) · Biological Psychology · doi:10.1016/j.biopsycho.2008.03.002 · Cited by 24
Real-time monitoring of serotonin with highly selective aptamer-functionalized conducting polymer nanohybrids
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Nutritional Interventions in Clinical Depression
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“Similar studies found decreased total tryptophan levels in patients of both genders with depression (Widner, Laich, Sperner-Unterweger, Ledochowski, & Fuchs, 2002; Young & Leyton, 2002).”
BackgroundResult
Cardio-autonomic control and wellbeing due to oscillating color light exposure
Grote, V., Kelz, C., Goswami, N., Stossier, H., Tafeit, E., & Moser, M. (2013) · Physiology & Behavior · doi:10.1016/j.physbeh.2013.03.007 · Cited by 22
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“…conditions such as obsessive–compulsive disorders (Feygin, Swain, & Leckman, 2006; Marazziti, Akiskal, Rossi, & Cassano, 1999), depression (Young & Leyton, 2002), and anxiety (Leonardo & Hen, 2006), suggesting that behaviors associated with intense early stage romantic love might share…”
Background
Hypoxia-related risk factors for death by suicide in a national clinical sample
Riblet, N. B. V., Gottlieb, D. J., Watts, B. V., Cornelius, S. L., Fan, V. S., Shi, X., & Shiner, B. R. (2019) · Psychiatry Research · doi:10.1016/j.psychres.2019.01.040 · Cited by 22
“Experimental manipulations to lower tryptophan in human have been shown to lower mood as well as increase irritability and aggression in some patients (McCloskey et al., 2009; Young and Leyton, 2002).”
Background
Dietary and botanical anxiolytics
Alramadhan, E., Hanna, M. S., Hanna, M. S., Goldstein, T. G., Avila, S. M., & Weeks, B. S. (2012) · Medical Science Monitor · doi:10.12659/msm.882608 · Cited by 23
Diet and companionship modulate pain via a serotonergic mechanism
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Unbalanced IDO1/IDO2 Endothelial Expression and Skewed Keynurenine Pathway in the Pathogenesis of COVID-19 and Post-COVID-19 Pneumonia
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Constitutive depletion of brain serotonin differentially affects rats’ social and cognitive abilities
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Neurochemical Markers in the Mammalian Brain: Structure, Roles in Synaptic Communication, and Pharmacological Relevance
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Neural Circuits, Neurotransmitters, and Behavior
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“, a 3-week calorie-reducing diet or acute tryptophan depletion) will produce greater alterations of 5-HT function or lowering of mood in women than in men (Goodwin et al. 1987; Young and Leyton 2002).”
Background
Mice deficient for wild-type p53-induced phosphatase 1 display elevated anxiety- and depression-like behaviors
Ruan, C. S., Zhou, F. H., He, Z. Y., Wang, S., Yang, C., Shen, Y., Guo, Y., Zhao, H., Chen, L., Liu, D., et al. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.02.037 · Cited by 22
Generation of a highly efficient and tissue-specific tryptophan hydroxylase 1 knockout mouse model
Kim, H., Kim, Y. G., Choi, W., Moon, J. H., Hwang, I., Kim, K., Yadav, V. K., Karsenty, G., Jeong, J.-S., & Kim, H. (2018) · Scientific Reports · doi:10.1038/s41598-018-36097-6 · Cited by 22
Molecular mechanisms underlying resting-state brain functional correlates of behavioral inhibition
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“Serotonin is a highly evolutionary conserved monoamine neurotransmitter that modulates multiple psychophysiological functions (Beliveau et al., 2017; King et al., 2008; Magalhaes et al., 2010; Young and Leyton, 2002).”
Background
The effects of intermittent theta burst stimulation (iTBS) on resting-state brain entropy (BEN)
Liu, P., Song, D., Deng, X., Shang, Y., Ge, Q., Wang, Z., & Zhang, H. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00556 · Cited by 19
Dietary l -tryptophan leaves a lasting impression on the brain and the stress response
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“Dietary manipulations have been used as tool to investigate the involvement of brain 5-HT in behaviour, mood and cognition in humans((3)).”
Investigation of serotonin, free and protein-bound tryptophan in Turkish hazelnut varieties and effect of roasting on serotonin content
Taş, N. G., Yılmaz, C., & Gökmen, V. (2018) · Food Research International · doi:10.1016/j.foodres.2018.11.051 · Cited by 20
Neurobehavioral effects of acute and chronic lead exposure in a desert rodent Meriones shawi: Involvement of serotonin and dopamine
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Impact of acute tryptophan depletion on mood and eating-related urges in bulimic and nonbulimic women
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“Other studies with ATD have also found a similar lowering of mood in healthy women.(33) An implication of the preceding may be that the role played by serotonin in regulating mood in women with bulimia does not differ markedly from the role it plays in healthy women.”
Self-citation
No effect of acute tryptophan depletion on verbal declarative memory in young persons with ADHD
Zepf, F. D., Landgraf, M., Biskup, C. S., Dahmen, B., Poustka, F., Wöckel, L., & Stadler, C. (2013) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12089 · Cited by 19
Effects of Acute Tryptophan Depletion on Three Different Types of Behavioral Impulsivity
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Dietary tryptophan supplementation and affective state in pigs
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“, 2012) and in the regulation of mood in general (Castanon, 2015; Young and Leyton, 2002).”
Background
Inhibition of hormonal and behavioral effects of stress by tryptophan in rats
Gul, S., Saleem, D. M., Haleem, M. A., & Haleem, D. J. (2017) · Nutritional Neuroscience · doi:10.1080/1028415x.2017.1395551 · Cited by 19
Electrodeposited reduced graphene oxide-PEDOT:PSS/Nafion hybrid interface for the simultaneous determination of dopamine and serotonin
Ko, S. H., Kim, S. W., Lee, S. H., & Lee, Y. J. (2023) · Scientific Reports · doi:10.1038/s41598-023-47693-6 · Cited by 18

Authors: Young, S. N., & Leyton, M.
Affiliations: McGill University (CA)
Corresponding author: Young, Simon N.
ORCID: Young, Simon N.
Leyton, Marco
Venue: Pharmacology Biochemistry and Behavior
Publisher: Elsevier BV
Published: 2002-04
Volume: 71
Issue: 4
Pages: 857-865
ISSN: 0091-3057 (ISSN-L)
DOI: 10.1016/s0091-3057(01)00670-0
OpenAlex: W1934200177
Cited by: 396
References: 127
Citations by year: 2026: 8 · 2025: 19 · 2024: 7 · 2023: 19 · 2022: 16 · 2021: 15 · 2020: 17 · 2019: 20 · 2018: 23 · 2017: 17 · 2016: 11 · 2015: 24 · 2014: 13 · 2013: 18 · 2012: 18
FWCI: 1.31
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacology Biochemistry and Behavior (publishedVersion)
PubMed (publishedVersion)
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 › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: serotonin, tryptophan, acute tryptophan depletion, mood, aggression, irritability, depression, social interaction, impulse control disorders, serotonin synthesis
MeSH terms: Affect, Humans, Interpersonal Relations, Serotonin, Tryptophan, Antidepressive Agents, Second-Generation

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The role of serotonin in human mood and social interaction

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