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The role of serotonin in human mood and social interaction
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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“A substantial body of literature implicates 5-HT neurotransmission in social processing and behavior (e.g. Del-Ben et al. 2008; Young and Leyton, 2002).”
From Effects of MDMA on sociability and neural response to social threat and social reward (2009) · cites this paper as Young and Leyton, 2002
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“This molecule is a derivative of tryptophan and can be metabolized into 5-hydroxytryptamine (5-HT), and activation of 5-HT receptors can lead to an increase in body temperature (69, 70).”
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Henry, J. S., Giribaldi, B., Nutt, D. J., Erritzøe, D., Carhart-Harris, R. L., & Lyons, T. (2025) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2025.06.003 · Cited by 5
Mohammed, S. G. A. A., & Qoronfleh, M. W. (2020) · Advances in neurobiology · doi:10.1007/978-3-030-30402-7_10 · Cited by 5
Brainstem Activity Predicts Attachment-Related Anxiety
Kikuchi, Y., Matsutani, Y., Mori, K., Hanada, K., Shirakawa, Y., Shirato, M., & Noriuchi, M. (2018) · Neuropsychiatry · doi:10.4172/neuropsychiatry.1000354 · Cited by 3
“Depletion of central serotonin is also found in several psychiatric disorders including obsessivecompulsive disorder (OCD) [43], depression [44], eating disorders [45], and anxiety disorders [46].”
Wang, J. S., Conley, Y. P., Sereika, S. M., Bender, C. M., Godbole, P., & Wesmiller, S. W. (2018) · Supportive Care in Cancer · doi:10.1007/s00520-018-4332-9 · Cited by 4
Bonassi, A., Carollo, A., Cataldo, I., Gabrieli, G., Tandiono, M., Foo, J. N., Lepri, B., & Esposito, G. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18147547 · Cited by 3
“In particular, serotonin seems to be crucial for social learning and interpersonal behavior, being positively associated with social dominance [28,29] and negatively correlated with aggression [30,31].”
BackgroundPriyadarshini, S., Pradhan, B., & Aich, P. (2018) · Biology Open · doi:10.1242/bio.034629 · Cited by 4
“Enterochromaffin cells in the gut-lining produce 95% of the body ’ s serotonin (Gli š ic ́ et al., 2006; Young and Leyton, 2002), and it is carried by platelets and mast-cells to the site of inflammation (Dürk et al., 2013; Peckett et al., 2011; Sepiashvili et al., 2013).”
Acute tryptophan depletion in healthy subjects increases preferences for negative reciprocity
Bengart, P., Gruendler, T. O. J., & Vogt, B. (2021) · PLoS ONE · doi:10.1371/journal.pone.0249339 · Cited by 5
“This measurement was included due to ATD’s reported effects on mood [35].”
MethodEating Disorders: Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder
Steiger, H., Bruce, K. R., & Israël, M. (2012) · Wiley eBooks · doi:10.1002/9781118133880.hop208003 · Cited by 4
Prevalence and Determinants of Cognitive Impairment: A Study from Punjab, North India
Yadav, N., Chaudhary, V., Saraswathy, K. N., & Devi, N. K. (2025) · Neurology India · doi:10.4103/neurol-india.neurol-india-d-23-00363 · Cited by 5
Therapeutic effects of positive emotions on neural pathways and neurotransmitter systems
El‐Mansoury, B., Laadraoui, J., Razouqi, Y., Haj-Khlifa, A., Fatimi, H. E., Hiba, O. E., & Jayakumar, A. R. (2025) · Progress in brain research · doi:10.1016/bs.pbr.2025.02.006 · Cited by 3
Luczynski, P., Neufeld, K. M., Clarke, G. A., Dinan, T. G., & Cryan, J. F. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802304-4.00007-4 · Cited by 3
Perreau-Linck, E., Beauregard, M., Gravel, P., Paquette, V., Soucy, J., Dikšić, M., & Benkelfat, C. (2007) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0743 · Cited by 3
van Donkelaar, E. L. (2013) · Translational Developmental Psychiatry · doi:10.3402/tdp.v1i0.18658 · Cited by 3
Dietary tryptophan depletion in humans using a simplified two amino acid formula – a pilot study
Linden, M., Helmbold, K., Kempf, J., Sippas, S., Filß, C., Langen, K., Eisert, A., & Zepf, F. D. (2016) · Food & Nutrition Research · doi:10.3402/fnr.v60.29272 · Cited by 3
Biological Vulnerabilities to the Development of Psychopathology
Pihl, R. O., & Nantel‐Vivier, A. (2005) · Sage eBooks · doi:10.4135/9781452231655.n4 · Cited by 3
Human Behavior During Spaceflight - Evidence From an Analog Environment
Arnaldi, K., Smith, G., & Thropp, J. E. (2015) · The Journal of Aviation/Aerospace Education and Research · doi:10.15394/jaaer.2015.1676 · Cited by 3
“Consuming doses of serotonin can help reduce aggressive behavior and promote social interactions (Young & Leyton, 2002).”
BackgroundKertzman, S., Vainder, M., Reznik, I., Gotzlav, Y., Weizman, A., Kotler, M., & Iancu, I. (2012) · International Clinical Psychopharmacology · doi:10.1097/yic.0b013e3283524d5c · Cited by 3
“Our results are also consistent with previous reports that demonstrated that low central serotonergic function is characterized by negative affective experience and lesser affiliative behavior (Knutson et al., 1998; Moskowitz et al., 2001; Tse and Bond, 2002; Young and Leyton, 2002).”
ResultOn the environmental genetics of depressive symptoms: Focus on two serotonergic genes
Jokela, M. M. (2007) · Työväentutkimus Vuosikirja · Cited by 3
Nod-like receptors are critical for gut-brain axis signalingPreprint
Pusceddu, M. M., Barboza, M., Schneider, M., Stokes, P., Sladek, J. A., Torres‐Fuentes, C., Goldfild, L. R., Gillis, S. E., Brust‐Mascher, I., Rabasa, G., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/647032 · Cited by 3
“and centrally produced 5-HT (44), and reduced serum Trp levels correlate with alterations in 405 mood and cognition (45, 46), serum Trp concentrations were assessed by LC/MS.”
Method
Metadata
- Authors
- Young, S. N., & Leyton, M.
- Affiliations
- McGill University (CA)
- Corresponding author
- Young, Simon N.
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 71
- Issue
- 4
- Pages
- 857-865
- ISSN
- 0091-3057 (ISSN-L)
- 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
- 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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