Riedel W J, Klaassen T, Deutz N E, van Someren A, van Praag H M
Department of Psychiatry and Neuropsychology, Brain and Behaviour Institute, European Graduate School for Neurosciences, Maastricht University, The Netherlands.
Psychopharmacology (Berl). 1999 Feb;141(4):362-9. doi: 10.1007/s002130050845.
Serotonin (5-hydroxytryptamine; 5-HT) circuits may play a role in cognitive performance, particularly in learning and memory. Cognitive impairment is often seen in depressed patients, in whom 5-HT turnover in the brain is thought to be lowered. A possible human pharmacological model to study the involvement of the serotonergic system in cognitive impairment is to reduce central 5-HT synthesis through L-tryptophan depletion in healthy subjects. In this study, the cognitive effects of tryptophan depletion were assessed and whether genetically or developmentally determined vulnerability factors were predictive of the cognitive impairment induced by tryptophan depletion. Sixteen healthy volunteers with a positive family history of depression and 11 without were given 100 g of an amino acid mixture with or without tryptophan, according to a double-blind, cross-over design. Tryptophan depletion specifically impaired long-term memory performance in all subjects: delayed recall performance, recognition sensitivity, and recognition reaction times were significantly impaired after tryptophan depletion relative to placebo. Short-term memory and perceptual and psychomotor functions were unchanged. There were no differences between groups with a positive and a negative family history for depression. On the basis of these results, it is concluded that tryptophan depletion specifically impairs long-term memory formation, presumably as a result of an acute decrease in 5-HT turnover in the brain.
血清素（5-羟色胺；5-HT）神经回路可能在认知表现中发挥作用，尤其是在学习和记忆方面。认知障碍在抑郁症患者中经常出现，这类患者大脑中的5-HT周转率被认为有所降低。一种用于研究血清素能系统与认知障碍关系的可能的人体药理学模型，是通过使健康受试者体内的L-色氨酸耗竭来减少中枢5-HT的合成。在本研究中，评估了色氨酸耗竭对认知的影响，以及遗传或发育决定的易感性因素是否可预测色氨酸耗竭所致的认知障碍。根据双盲交叉设计，对16名有抑郁症家族史的健康志愿者和11名无抑郁症家族史的健康志愿者给予100克含或不含色氨酸的氨基酸混合物。色氨酸耗竭特异性损害了所有受试者的长期记忆表现：相对于安慰剂，色氨酸耗竭后延迟回忆表现、识别敏感性和识别反应时间均显著受损。短期记忆以及感知和精神运动功能未发生变化。有抑郁症家族史阳性和阴性的两组之间没有差异。基于这些结果，得出结论：色氨酸耗竭特异性损害长期记忆形成，这可能是大脑中5-HT周转率急性降低的结果。
