Neural response to catecholamine depletion in unmedicated subjects with major depressive disorder in remission and healthy subjects
Neural response to catecholamine depletion in unmedicated subjects with major depressive disorder in remission and healthy subjects
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未服药的重度抑郁症缓解期患者和健康人对儿茶酚胺消耗的神经反应
DOI：
10.1001/archpsyc.65.5.521
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发表时间：
2008-05-01
影响因子：
--
通讯作者：
Drevets, Wayne C.
中科院分区：
文献类型：
--
作者：
Hasler, Gregor;Fromm, Stephen;Drevets, Wayne C.
背景：各种间接证据表明，重度抑郁症（MDD）的病理生理机制一直与儿茶酚胺能功能改变有关，尤其是多巴胺神经传递减少。儿茶酚胺能功能与抑郁之间关系的一个更直接的研究范式涉及实验性儿茶酚胺耗竭（CD）的情绪反应。目的：确定儿茶酚胺能功能障碍是否代表MDD的一种特征异常，并确定参与MDD病理生理机制的脑回路异常。设计：随机、双盲、安慰剂对照、交叉、单点试验。地点：精神科门诊。参与者：15名未服药且完全缓解的重度抑郁症患者（以下简称RMDD患者）和13名健康对照者。干预：通过口服α -甲基对酪氨酸诱导CD。假消耗使用含有含水乳糖的相同胶囊。主要观察指标：定量脑葡萄糖利用正电子发射断层扫描研究CD和假性耗竭对神经系统的影响。行为评估包括蒙哥马利-阿斯伯格抑郁评定量表和斯奈斯-汉密尔顿快乐量表（快感缺乏）。结果：与对照组相比，RMDD受试者在CD期间抑郁和快感缺乏症状增加的程度更大。在两组中，CD增加了前腹侧纹状体的代谢，降低了眶回的代谢。在由腹内侧额极皮层、扣带中皮层和亚属前扣带皮层、颞极皮层、腹侧纹状体和丘脑组成的边缘-皮质-纹状体-丘脑网络中，RMDD受试者的代谢增加，但对照组的代谢减少或保持不变。CD诱导的左腹内侧额极皮质代谢变化与抑郁症状呈正相关，而前腹内侧纹状体代谢变化与快感缺乏症相关。结论：本研究为儿茶酚胺能功能障碍作为重度抑郁症的一种特征异常提供了直接证据。研究表明，由于儿茶酚胺能神经传递减少而导致的抑郁和快感缺乏症状与边缘-皮质-纹状体-苍白-丘脑回路内活动升高有关。
Context: The pathophysiologic mechanism of major depressive disorder (MDD) has been consistently associated with altered catecholaminergic function, especially with decreased dopamine neurotransmission, by various sources of largely indirect evidence. An instructive paradigm for more directly investigating the relationship between catecholaminergic function and depression has involved the mood response to experimental catecholamine depletion (CD).Objectives: To determine whether catecholaminergic dysfunction represents a trait abnormality in MDD and to identify brain circuitry abnormalities involved in the pathophysiologic mechanism of MDD.Design: Randomized, double-blind, placebo-controlled, crossover, single-site experimental trial.Setting: Psychiatric outpatient clinic.Participants: Fifteen unmedicated subjects with MDD in full remission (hereinafter referred to as RMDD subjects) and 13 healthy controls.Intervention: Induction of CD by oral administration of alpha-methylparatyrosine. Sham depletion used identical capsules containing hydrous lactose.Main Outcome Measures: Quantitative positron emission tomography of regional cerebral glucose utilization to study the neural effects of CD and sham depletion. Behavioral assessments included the Montgomery-Asberg Depression Rating Scale and the Snaith-Hamilton Pleasure Scale (anhedonia).Results: Depressive and anhedonic symptoms increased during CD to a greater extent in RMDD subjects than in controls. In both groups, CD increased metabolism in the anteroventral striatum and decreased metabolism in the orbital gyri. In a limbic-cortical-striatal-pallidal-thalamic network previously implicated in MDD, composed of the ventromedial frontal polar cortex, midcingulate and subgenual anterior cingulate cortex, temporopolar cortex, ventral striatum, and thalamus, metabolism increased in RMDD subjects but decreased or remained unchanged in controls. Metabolic changes induced by CD in the left ventromedial frontal polar cortex correlated positively with depressive symptoms, whereas changes in the anteroventral striatum were correlated with anhedonic symptoms.Conclusions: This study provides direct evidence for catecholaminergic dysfunction as a trait abnormality in MDD. it demonstrates that depressive and anhedonic symptoms as a result of decreased catecholaminergic neurotransmission are related to elevated activity within the limbic-cortical-striatal-pallidal-thalamic circuitry.