McLean Andrew, Rubinsztein Judy S, Robbins Trevor W, Sahakian Barbara J
Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
Psychopharmacology (Berl). 2004 Jan;171(3):286-97. doi: 10.1007/s00213-003-1586-8. Epub 2003 Sep 4.
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 (T(0)) and 5 h following consumption (T(5)) of the mixtures. A comprehensive neuropsychological test battery was also administered at T(5).
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.
近年来，人们对多巴胺（DA）在单相抑郁症发病机制及动机行为中的作用越来越感兴趣。急性酪氨酸耗竭这一创新技术为进一步阐明其在这些领域的功能提供了契机。
本研究考察了急性酪氨酸耗竭对健康志愿者生理、主观及认知方面的影响。
采用双盲、安慰剂对照、平行组设计。一半参与者摄入平衡氨基酸混合物（BAL），另一半则摄入除不含酪氨酸和苯丙氨酸外其他成分相同的混合物（无酪氨酸组）。在摄入混合物的基线期（T(0)）及5小时后（T(5)）监测血浆氨基酸浓度及主观评分。在T(5)时还进行了一套全面的神经心理学测试。
与BAL组相比，无酪氨酸组大脑酪氨酸可利用性的降低更为显著。心理评定量表的使用结果显示，与BAL组相比，无酪氨酸组变得不那么满足且更加冷漠。对于情感性停止信号任务，BAL组表现出愉快潜伏期偏差，而无酪氨酸组表现出悲伤潜伏期偏差。此外，在决策任务中，无酪氨酸组根据更可能的结果增加赌注的速度低于BAL组。综合来看，这些神经心理学发现与先前对单相抑郁症的研究结果惊人地相似。在包括额叶执行功能更经典评估在内的任何其他神经心理学指标上，实验组之间均无差异。
这些发现与多巴胺能因素特别参与临床抑郁症特征性的情感/奖赏相关加工障碍这一假说一致。
