Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women
Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women
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DOI：
10.1001/archpsyc.63.11.1199
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发表时间：
2006-11-01
影响因子：
--
通讯作者：
Zubieta, Jon-Kar
中科院分区：
文献类型：
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作者：
Kennedy, Susan E.;Koeppe, Robert A.;Zubieta, Jon-Kar
背景：有大量证据表明，人类重度抑郁症（MDD）的病理生理机制中存在应激反应和应激适应功能障碍。内源性阿片神经传递激活mu-阿片受体参与应激和情绪调节过程，并进一步与重度抑郁症有关。目的：探讨多阿片神经递质在重度抑郁症患者情感状态调节中的作用及其与抗抑郁治疗临床反应的关系。设计：通过正电子发射断层扫描和中性状态下的mu-阿片受体选择性放射性示踪剂碳11标记的卡芬太尼，获得了体内mu-阿片受体可用性（结合电位[BP]）的测量。通过将持续悲伤挑战与中性状态进行比较，获得了持续悲伤挑战期间BP的变化，反映了这种情绪体验期间内源性阿片神经传递的变化。环境：大学医疗中心的诊所和神经成像设施。参与者：14名健康女性志愿者和14名被诊断为重度抑郁症的患者志愿者通过广告和门诊诊所招募。干预措施：持续的中性和悲伤状态，随机和平衡顺序，由提示回忆与该情绪相关的自传体事件引起。在影像学检查后，患者接受20 - 40mg盐酸氟西汀的10周疗程。主要结局指标：中性和持续悲伤状态时mu-阿片受体BP的变化，消极和积极影响评分，血浆皮质醇和促肾上腺皮质激素水平，以及抗抑郁药物的临床反应。结果：持续悲伤状态与重度抑郁症患者左侧下颞叶皮层mu-阿片受体BP下降相关，并与抑郁期间经历的负面情绪评分相关。相反，在健康对照组中，在前扣带吻侧区观察到明显增加的mu-阿片受体BP。在该区域，对抗抑郁药物治疗无效的MDD患者在悲伤期间观察到mu-阿片受体BP显著下降。MDD患者与对照组的比较显示，MDD患者后丘脑中性状态mu-阿片受体BP显著降低，与促肾上腺皮质激素和皮质醇血浆水平相关。悲伤时，MDD患者在岛叶前部皮层、丘脑前部和后部、基底神经节腹侧、杏仁核和杏仁核周围皮层的mu-阿片系统血压有较大的降低。同样的挑战引起对照组前扣带、腹侧基底神经节、下丘脑、杏仁核和杏仁核周围皮层的血压测量更大的增加。结论：研究结果表明MDD女性和对照组女性在中性状态下的mu-阿片受体可用性存在差异，而在实验诱导的持续悲伤状态下，该神经递质系统的反应则相反。这些数据表明，在诊断为重度抑郁症的患者中，与应激反应和情绪调节有关的mu-阿片受体的内源性阿片神经传递发生了改变。
Context: There is extensive evidence implicating dysfunctions in stress responses and adaptation to stress in the pathophysiological mechanism of major depressive disorder (MDD) in humans. Endogenous opioid neurotransmission activating mu-opioid receptors is involved in stress and emotion regulatory processes and has been further implicated in MDD.Objective: To examine the involvement of mu-opioid neurotransmission in the regulation of affective states in volunteers with MDD and its relationship with clinical response to antidepressant treatment.Design: Measures of mu-opioid receptor availability in vivo ( binding potential [BP]) were obtained with positron emission tomography and the mu-opioid receptor selective radiotracer carbon 11-labeled carfentanil during a neutral state. Changes in BP during a sustained sadness challenge were obtained by comparing it with the neutral state, reflecting changes in endogenous opioid neurotransmission during the experience of that emotion.Setting: Clinics and neuroimaging facilities at a university medical center.Participants: Fourteen healthy female volunteers and 14 individually matched patient volunteers diagnosed with MDD were recruited via advertisement and through outpatient clinics.Interventions: Sustained neutral and sadness states, randomized and counterbalanced in order, elicited by the cued recall of an autobiographical event associated with that emotion. Following imaging procedures, patients underwent a 10-week course of treatment with 20 to 40 mg of fluoxetine hydrochloride.Main Outcome Measures: Changes in mu-opioid receptor BP during neutral and sustained sadness states, negative and positive affect ratings, plasma cortisol and corticotropin levels, and clinical response to antidepressant administration.Results: The sustained sadness condition was associated with a statistically significant decrease in mu-opioid receptor BP in the left inferior temporal cortex of patients with MDD and correlated with negative affect ratings experienced during the condition. Conversely, a significant increase in mu-opioid receptor BP was observed in healthy control subjects in the rostral region of the anterior cingulate. In this region, a significant decrease in mu-opioid receptor BP during sadness was observed in patients with MDD who did not respond to antidepressant treatment. Comparisons between patients with MDD and controls showed significantly lower neutral-state mu-opioid receptor BP in patients with MDD in the posterior thalamus, correlating with corticotropin and cortisol plasma levels. Larger reductions in mu-opioid system BP during sadness were obtained in patients with MDD in the anterior insular cortex, anterior and posterior thalamus, ventral basal ganglia, amygdala, and periamygdalar cortex. The same challenge elicited larger increases in the BP measure in the control group in the anterior cingulate, ventral basal ganglia, hypothalamus, amygdala, and periamygdalar cortex.Conclusions: The results demonstrate differences between women with MDD and control women in mu-opioid receptor availability during a neutral state, as well as opposite responses of this neurotransmitter system during the experimental induction of a sustained sadness state. These data demonstrate that endogenous opioid neurotransmission on mu-opioid receptors, a system implicated in stress responses and emotional regulation, is altered in patients diagnosed with MDD.