Serotonin and the neurobiology of depression. Effects of tryptophan depletion in drug-free depressed patients.
Serotonin and the neurobiology of depression. Effects of tryptophan depletion in drug-free depressed patients.
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DOI：
10.1001/archpsyc.1994.03950110025005
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发表时间：
1994-11
影响因子：
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通讯作者：
P. Delgado;L. Price;H. Miller;R. Salomon;G. Aghajanian;G. Heninger;D. Charney
中科院分区：
文献类型：
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作者：
P. Delgado;L. Price;H. Miller;R. Salomon;G. Aghajanian;G. Heninger;D. Charney
目的探讨色氨酸耗竭对未经治疗的抑郁症患者的影响。饮食中5-羟色胺合成的前体色氨酸的快速消耗，导致67%的抗抑郁治疗反应的患者短暂恢复抑郁。方法43例未经治疗的抑郁症患者在一项双盲、安慰剂对照的交叉研究中接受色氨酸耗竭。测试后，他们接受了开放式序贯抗抑郁治疗。结果：色氨酸耗竭后，受试者的情绪没有变化，但在耗竭试验后的第二天发生了变化。相对于对照试验，37%的患者的汉密尔顿抑郁评定量表（Ham-D）评分下降10分或更多，而23%的患者在色氨酸耗竭试验后的第二天Ham-D评分增加10分或更多。测试后情绪的变化与治疗反应相关。病情恶化的患者被证明对治疗非常难治，而那些表现出改善的患者更有可能做出反应。结论：色氨酸缺乏并没有迅速恶化抑郁症，这表明5-羟色胺功能与抑郁症的水平不是线性相关的，如果5-羟色胺功能降低确实导致抑郁症，那么它要么是诱发因素，要么是由于5-羟色胺利用的突触后缺陷。
OBJECTIVE To investigate the effects of tryptophan depletion in untreated depressed patients. Rapid dietary depletion of the precursor of serotonin synthesis, tryptophan, causes a transient return of depression in 67% of patients who have had a therapeutic antidepressant response. METHOD Forty-three untreated depressed patients underwent tryptophan depletion in a double-blind, placebo-controlled cross-over study. After testing, they received open sequential antidepressant treatment. RESULTS Mood did not change when tryptophan was depleted but did change on the day after the depletion test. Relative to the control test, 37% of the patients had 10-point or greater decrease in Hamilton Depression Rating Scale (Ham-D) score, while 23% had a 10-point or greater increase in Ham-D score on the day after the tryptophan depletion test. Change in mood was correlated to treatment response after testing. Patients whose condition worsened proved to be highly refractory to treatment while those who showed improvement were more likely to respond. CONCLUSIONS That tryptophan depletion did not rapidly worsen depression argues that serotonin function is not linearly related to the level of depression and if reduced serotonin function does cause depression, then it is either as predisposing factor or due to a postsynaptic deficit in the utilization of serotonin.