The effects of tyrosine depletion in normal healthy volunteers: implications for unipolar depression
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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.
The present study examined the physiological, subjective and cognitive effects of acute tyrosine depletion in healthy volunteers.
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 (T0) and 5 h following consumption (T5) of the mixtures. A comprehensive neuropsychological test battery was also administered at T5.
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.
These findings are consistent with the hypothesis that dopaminergic factors are particularly involved in disrupted affect/reward-based processing characteristic of clinical depression.
KeywordsTyrosine Depletion Dopamine Neuropsychology Reward Affective processing
We thank the volunteers for participating and the staff of ward R4 for their assistance and patience. The study was funded by a Wellcome Trust Programme Grant awarded to Professors Trevor Robbins, Barry Everitt and Barbara Sahakian, and Dr. Angela Roberts, and was completed within the MRC Centre for Behavioural and Cognitive Neuroscience. A.M. was supported by a MRC Research Studentship and J.S.R. was the recipient of the Betty Behrens Research Fellowship at Clare Hall, Cambridge, and received a Sackler studentship. We thank Dr. Sarah McTavish for methodological advice and Dr. Mike Franklin and his team for performing the biochemical analyses of the blood samples.
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