Neumeister Alexander, Hu Xian-Zhang, Luckenbaugh David A, Schwarz Markus, Nugent Allison C, Bonne Omer, Herscovitch Peter, Goldman David, Drevets Wayne C, Charney Dennis S
Molecular Imaging Program of the Clinical Neuroscience Division, Department of Psychiatry, Yale University School of Medicine, 950 Campbell Avenue, West Haven, CT 06516, USA.
Arch Gen Psychiatry. 2006 Sep;63(9):978-86. doi: 10.1001/archpsyc.63.9.978.
Tryptophan depletion (TD) is a model used to study the contribution of reduced serotonin transmission to the pathogenesis of major depressive disorder (MDD). Recent studies have not sufficiently addressed the relative contribution of a functional-length triallelic polymorphism in the promoter of the serotonin transporter, 5-HTTLPR, to the behavioral and neural responses to TD in individuals with remitted MDD (rMDD) and controls.
To determine the role of 5-HTTLPR on the behavioral and neural responses to TD in medication-free patients with rMDD and individually matched controls.
Participants were stratified according to diagnosis and 5-HTTLPR genotypes and underwent TD on one test day and sham depletion on the other test day in a prospective, double-blind, randomized order.
Outpatient clinic.
Twenty-seven medication-free patients with rMDD (18 women and 9 men) and 26 controls (17 women and 9 men).
Tryptophan depletion was induced by administration of capsules containing an amino acid mixture without tryptophan. Sham depletion used identical capsules containing lactose. Fludeoxyglucose F 18 positron emission tomography was performed 6 hours after TD. Magnetic resonance images were obtained for each participant.
Quantitative positron emission tomography of regional cerebral metabolic rates for glucose and measures of depression using the Hamilton Depression Rating Scale.
Behavioral responses to TD are affected by 5-HTTLPR in patients with rMDD and controls. A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex.
Variations in 5-HTTLPR modulate the sensitivity of patients with rMDD and controls to the behavioral effects of TD. In patients with rMDD, variations in triallelic 5-HTTLPR have a direct effect on regulation of regional cerebral metabolic rates for glucose in a corticolimbic circuit that has been implicated in rMDD.
色氨酸耗竭（TD）是一种用于研究血清素传递减少对重度抑郁症（MDD）发病机制影响的模型。近期研究尚未充分探讨血清素转运体启动子区功能性长度三态性多态性（5-HTTLPR）对缓解期MDD（rMDD）患者及对照者对TD的行为和神经反应的相对贡献。
确定5-HTTLPR在未服药的rMDD患者及个体匹配对照者对TD的行为和神经反应中的作用。
参与者根据诊断和5-HTTLPR基因型进行分层，并在前瞻性、双盲、随机顺序下，在一个测试日接受TD，在另一个测试日接受假耗竭。
门诊诊所。
27名未服药的rMDD患者（18名女性和9名男性）和26名对照者（17名女性和9名男性）。
通过给予不含色氨酸的氨基酸混合物胶囊诱导色氨酸耗竭。假耗竭使用含乳糖的相同胶囊。TD后6小时进行氟脱氧葡萄糖F 18正电子发射断层扫描。为每位参与者获取磁共振图像。
葡萄糖区域脑代谢率的定量正电子发射断层扫描以及使用汉密尔顿抑郁量表测量抑郁情况。
rMDD患者及对照者对TD的行为反应受5-HTTLPR影响。在rMDD患者中，发现5-HTTLPR对杏仁核、海马体和膝下前扣带回皮质的葡萄糖区域脑代谢率调节有直接影响。
5-HTTLPR的变异调节rMDD患者及对照者对TD行为效应的敏感性。在rMDD患者中，三态性5-HTTLPR的变异对涉及rMDD的皮质边缘回路中葡萄糖区域脑代谢率的调节有直接影响。
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