Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls
Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls
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DOI：
10.1001/archpsyc.61.8.765
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发表时间：
2004-08-01
影响因子：
--
通讯作者：
Drevets, WC
中科院分区：
文献类型：
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作者：
Neumeister, A;Nugent, AC;Drevets, WC
内容：研究脑5-羟色胺功能与重性抑郁症（MDD）之间关系的一个有指导意义的范例是对色氨酸耗竭（TD）的反应，色氨酸耗竭是由口服负荷除5-羟色胺前体色氨酸以外的所有必需氨基酸引起的。目的：确定5-羟色胺功能障碍是否代表MDD中的一种特质异常，其背景是特定神经回路异常参与MDD的发病机制。设计：随机双盲交叉研究。设置：门诊。参与者：27例无药物治疗的MDD缓解患者（18名女性和9名男性;平均+/- SD年龄，39.8 ± 12.7岁）和19名对照（10名女性和9名男性;平均SD年龄，34.4 +/-11.5岁）。干预：我们通过施用含有不含色氨酸的氨基酸混合物的胶囊来诱导TD。假消耗使用含有含水乳糖的相同胶囊。TD后6小时进行氟脱氧葡萄糖F18正电子发射断层扫描研究。磁共振成像获得所有participant.Main结果Measures：定量正电子发射断层扫描的区域脑葡萄糖利用率，研究假耗竭和TD的神经效应。行为评估使用修改后的（24项）版本的汉密尔顿抑郁量表。结果：色氨酸耗竭引起抑郁症状的缓解患者，但在对照组中没有短暂的回报（P <0.001）。与假耗竭相比，TD与缓解的MDD患者的眶额皮质、内侧丘脑、前扣带皮质和后扣带皮质以及腹侧纹状体的局部脑葡萄糖利用率增加相关，但在对照组中不相关。TD诱导的MDD缓解患者局部脑葡萄糖利用变化的模式表明，TD揭示了一种疾病特异性，5-羟色胺系统相关的特质功能障碍，并确定了一个电路，可能在MDD的发病机制中发挥关键作用。
Context: An instructive paradigm for investigating the relationship between brain serotonin function and major depressive disorder (MDD) is the response to tryptophan depletion (TD) induced by oral loading with all essential amino acids except the serotonin precursor tryptophan.Objective: To determine whether serotonin dysfunction represents a trait abnormality in MDD in the context of specific neural circuitry abnormalities involved in the pathogenesis of MDD.Design: Randomized double-blind crossover study.Setting: Outpatient clinic.Participants: Twenty-seven medication-free patients with remitted MDD (18 women and 9 men; mean +/- SD age, 39.8 +/- 12.7 years) and 19 controls (10 women and 9 men; mean SD age, 34.4 +/- 11.5 years).Interventions: We induced TD, by administering capsules containing an amino acid mixture without tryptophan. Sham depletion used identical capsules containing hydrous lactose. Fluorodeoxyglucose F 18 positron emission tomography studies were performed 6 hours after TD. Magnetic resonance images were obtained for all participants.Main Outcome Measures: Quantitative Positron emission tomography of regional cerebral glucose utilization to study the neural effects of sham depletion and TD. Behavioral assessments used a modified (24-item) version of the Hamilton Depression Rating Scale.Results: Tryptophan depletion induced a transient return of depressive symptoms in patients with remitted MDD but not in controls (P < .001). Compared with sham depletion, TD was associated with an increase in regional cerebral glucose utilization in the orbitofrontal cortex, medial thalamus, anterior and posterior cingulate cortices, and ventral striatum in patients with remitted MDD but not in controls.Conclusion: The pattern of TD-induced regional-cerebral glucose utilization changes in patients with remitted MDD suggests that TD unmasks a disease-specific, serotonin system-related trait dysfunction and identifies a circuit that probably plays a key role in the pathogenesis of MDD.