Principles of Rapid Tryptophan Depletion and its Use in Research on Neuropsychiatric Disorders

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Serotonin (5-HT) is a neurotransmitter which plays an important role in many psychiatric disorders. Existing evidence on the central nervous effects of 5-HT relies to a great extent on pharmacological investigations. Many studies used the administration of selective serotonin reuptake inhibitors (SSRI), which allow the investigation of how an increase in central nervous 5-HT neurotransmission influences behavioural characteristics and neural functioning. However, in order to achieve a central nervous dysfunction in 5-HT neurotransmission in animals and humans, a different approach called rapid tryptophan depletion (RTD) can be used. The fundamental concept of RTD builds on the administration of a tryptophan-free diet within an amino acid drink lacking tryptophan, the physiological precursor amino acid of 5-HT. RTD allows a short-term depletion of 5-HT synthesis in the brain. Following this there is a close link between nutritional intake of essential large neutral amino acids (such as tryptophan) and serotonergic neurotransmission in humans. The depletion of central nervous 5-HT allows the study of behavioural and neural effects of this deficit by combining RTD with behavioural test procedures, genetic markers, and imaging techniques. The data obtained under depleted conditions in such studies can serve as a human model for a central nervous 5-HT deficit, which is thought to play a decisive role in a variety of neuropsychiatric disorders. The following chapter gives an overview on the basic principles of RTD and how it can be used in an experiment involving both healthy subjects and patient populations.
Original languageEnglish
Title of host publicationAmino Acids in Human Nutrition and Health
EditorsJ.P.F. D'Mello
Place of PublicationOxfordshire
PublisherCABI Publishing
ISBN (Print)9781845937980
Publication statusPublished - 2012
Externally publishedYes


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