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Cited by 125Neurotransmitter Receptor Influence on BehaviorTryptophan and brain disordersTreatment of Major Depression

The effects of tyrosine depletion in normal healthy volunteers: implications for unipolar depression

McLean, Andrew, Rubinsztein, Judy S., Robbins, Trevor W., Sahakian, Barbara J.·2004·Psychopharmacology
DOI 10.1007/s00213-003-1586-8
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Abstract

Rationale In recent years, there has been a growing interest in the role of dopamine (DA) both in the pathogenesis of unipolar depression and in motivated behaviour. The innovative technique of acute tyrosine depletion presents an opportunity to characterise further its function in these domains.Objective The present study examined the physiological, subjective and cognitive effects of acute tyrosine depletion in healthy volunteers.Methods A double-blind, placebo-controlled, parallel group design was employed. Half of the participants ingested a balanced amino-acid mixture (BAL) and the other half received an identical mixture except that tyrosine and phenylalanine were absent (TYR-free). Plasma amino acid concentrations and subjective ratings were monitored at both baseline (T(0)) and 5 h following consumption (T(5)) of the mixtures. A comprehensive neuropsychological test battery was also administered at T(5).Results Relative to the BAL group, the reduction in TYR availability to the brain was more marked in the TYR-free group. Employment of psychological rating scales revealed that, compared with the BAL group, the TYR-free group became less content and more apathetic. For the affective go/no-go task, whilst the BAL group exhibited a happy latency bias, the TYR-free group demonstrated a sad latency bias. Furthermore, in the decision-making task, the rate at which the TYR-free group increased their bets in response to more likely outcomes was lower than that of the BAL group. Taken together, these neuropsychological findings strikingly paralleled those reported in previous investigations of unipolar depression. The experimental groups could not be differentiated on any of the other neuropsychological measures, including more classical assessments of fronto-executive function.Conclusion These findings are consistent with the hypothesis that dopaminergic factors are particularly involved in disrupted affect/reward-based processing characteristic of clinical depression.

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  • Tyrosine depletion experiments suggest that acute reductions in brain catecholamine levels lead people to behave in a less motivated way or to develop cognitive impairments.

    “In line with this, tyrosine depletion experiments, in which participants consume an amino acid mixture devoid of tyrosine and its precursor, phenylalanine, suggest that acute reductions in brain catecholamine levels lead people to behave in a less motivated way (McLean et al., 2004;Roiser et al., 2005;Cawley et al., 2013) or develop cognitive impairments (Harmer et al., 2001).”

    From Behavioral and cognitive effects of tyrosine intake in healthy human adults (2015) · cites this paper as McLean et al., 2004

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Authors
McLean, A., Rubinsztein, J. S., Robbins, T. W., & Sahakian, B. J.
Affiliations
University of Cambridge (GB)
Corresponding author
Sahakian, Barbara J.
ORCID
Venue
Psychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2004-01-01
Volume
171
Issue
3
Pages
286-297
ISSN
  • 0033-3158 (ISSN-L)
  • 1432-2072
DOI
10.1007/s00213-003-1586-8
OpenAlex
W1988574111
Cited by
125
References
79
Citations by year
2026: 3 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 10 · 2019: 3 · 2018: 8 · 2017: 5 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 8 · 2012: 6
FWCI
2.93
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Psychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Wellcome Trust
  • Medical Research Council
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
major depressive disorder, dopamine, phenylalanine, plasma amino acids, affective go/no-go task, decision-making, reward processing, apathy, motivated behavior, healthy volunteers
MeSH terms
Adult, Analysis of Variance, Cognition, Depressive Disorder, Double-Blind Method, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Tyrosine, Statistics, Nonparametric

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