Ruhé H G, Mason N S, Schene A H
Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Mol Psychiatry. 2007 Apr;12(4):331-59. doi: 10.1038/sj.mp.4001949. Epub 2007 Jan 16.
Dysfunction in the monoamine systems of serotonin (5-HT), norepinephrine (NE) and dopamine (DA) may causally be related to major depressive disorder (MDD). Monoamine depletion studies investigate the direct effects of monoamines on mood. Acute tryptophan depletion (ATD) or para-chlorophenylalanine (PCPA) deplete 5-HT, acute phenylalanine/tyrosine depletion (APTD) or alpha-methyl-para-tyrosine (AMPT) deplete NE/DA. Available depletion studies found conflicting results in heterogeneous populations: healthy controls, patients with previous MDD in remission and patients suffering from MDD. The decrease in mood after 5-HT and NE/DA depletion in humans is reviewed and quantified. Systematic search of MEDLINE and EMBASE (1966-October 2006) and cross-references was carried out. Randomized studies applying ATD, PCPA, APTD or AMPT vs control depletion were included. Pooling of results by meta-analyses was stratified for studied population and design of the study (within or between subjects). Seventy-three ATD, 2 PCPA, 10 APTD and 8 AMPT studies were identified of which 45 ATD and 8 APTD studies could be meta-analyzed. 5-HT or NE/DA depletion did not decrease mood in healthy controls. 5-HT or NE/DA depletion slightly lowered mood in healthy controls with a family history of MDD. In drug-free patients with MDD in remission, a moderate mood decrease was found for ATD, without an effect of APTD. ATD induced relapse in patients with MDD in remission who used serotonergic antidepressants. In conclusion, monoamine depletion studies demonstrate decreased mood in subjects with a family history of MDD and in drug-free patients with MDD in remission, but do not decrease mood in healthy humans. Although depletion studies usefully investigate the etiological link of 5-HT and NE with MDD, they fail to demonstrate a causal relation. They presumably clarify a vulnerability trait to become depressed. Directions for further investigation of this vulnerability trait are proposed.
血清素（5-羟色胺，5-HT）、去甲肾上腺素（NE）和多巴胺（DA）单胺系统功能障碍可能与重度抑郁症（MDD）存在因果关系。单胺耗竭研究旨在探究单胺对情绪的直接影响。急性色氨酸耗竭（ATD）或对氯苯丙氨酸（PCPA）可耗尽5-HT，急性苯丙氨酸/酪氨酸耗竭（APTD）或α-甲基对酪氨酸（AMPT）可耗尽NE/DA。现有的耗竭研究在异质性人群（健康对照者、既往MDD缓解期患者和MDD患者）中得出了相互矛盾的结果。本文对人体5-HT以及NE/DA耗竭后情绪的下降情况进行了综述和量化。我们系统检索了MEDLINE和EMBASE数据库（1966年至2006年10月）及相关参考文献。纳入了应用ATD、PCPA、APTD或AMPT与对照耗竭的随机研究。通过荟萃分析汇总结果，并根据研究人群和研究设计（受试者内或受试者间）进行分层。共识别出73项ATD研究、2项PCPA研究、10项APTD研究和8项AMPT研究，其中45项ATD研究和8项APTD研究可进行荟萃分析。5-HT或NE/DA耗竭并未使健康对照者的情绪下降。5-HT或NE/DA耗竭使有MDD家族史的健康对照者的情绪略有降低。在未服用药物的MDD缓解期患者中，发现ATD可使情绪适度下降，而APTD则无此作用。ATD可导致正在使用5-羟色胺能抗抑郁药的MDD缓解期患者复发。总之，单胺耗竭研究表明，有MDD家族史的受试者以及未服用药物的MDD缓解期患者的情绪会下降，但健康人不会。尽管耗竭研究有效地探究了5-HT和NE与MDD的病因学联系，但未能证明它们之间存在因果关系。它们可能阐明了一种易患抑郁症的脆弱特质。本文提出了进一步研究这种脆弱特质的方向。
