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The Effects of Acute Tryptophan Depletion on Neuropsychological Function

University of Newcastle upon Tyne, Department of Psychiatry, The Royal Victoria Infirmary, Newcastle upon Tyne, UK

Peter Gallagher

University of Newcastle Upon Tyne, Department of Psychiatry, The Royal Victoria Infirmary, Newcastle Upon Tyne, UK

Mary E. Stewart

University of Newcastle Upon Tyne, Department of Psychiatry, The Royal Victoria Infirmary, Newcastle upon Tyne, UK

David Matthews

University of Newcastle Upon Tyne, Department of Psychiatry, The Royal Victoria Infirmary, Newcastle Upon Tyne, UK

Tom P. Kelly

University of Newcastle Upon Tyne, Department of Psychiatry, The Royal Victoria Infirmary, Newcastle Upon Tyne, UK

Allan H. Young

University of Newcastle Upon Tyne, Department of Psychiatry, The Royal Victoria Infirmary, Newcastle Upon Tyne, UK, a.h.young{at}ncl.ac.uk

Serotonin (5-HT, 5-hydroxytryptamine) may have an important role in the maintenance of normal neuropsychological functioning. The method of acute tryptophan depletion (ATD) provides a pharmacological challenge by which central 5-HT levels can be temporarily decreased and effects on learning, memory and mood examined. Twenty healthy male volunteers were recruited to take part in this within-subject, double-blind, crossover study. Neuropsychological function was evaluated 4-6 h after ingestion of a control or 52 g tryptophan (TRP) depleting amino-acid drink. ATD significantly lowered levels of plasma total and free TRP (p < 0.001), but this did not affect mood or performance on tests of verbal and visuo-spatial learning and memory, attention or executive function. These results contradict previous findings; however, the degree of disruption of central 5-HT levels resulting from the use of the 52 g amino-acid protocol may be an important factor in explaining the lack of effect. By utilizing more specific probes of individual 5-HT receptor subtypes, future studies can fully explore the role of 5-HT in neuropsychological functioning and may elucidate the factors determining vulnerability to the effects of serotonergic dysfunction.

Key Words: acute tryptophan depletion • attention • CANTAB • learning • memory • mood • serotonin

Journal of Psychopharmacology, Vol. 17, No. 3, 300-309 (2003)
DOI: 10.1177/02698811030173012


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