Vagus Nerve Stimulation for Depression: PET Studies

描述（由申请人提供）：重度抑郁症（MOD）是美国致残的主要原因。大约20%的MOD患者（约400万美国人）在反复的抗抑郁药（AD）试验中失败，导致“治疗难治性抑郁症”（TRD）。治疗TRD的有效方法很少。即使是电惊厥治疗（ECT）对TRD的疗效也较差，-68%接受ECT治疗的TRD患者在一年内复发为重度抑郁症。2005年，美国食品药品监督管理局批准了trd用于迷走神经刺激（VMS）的特异性适应症。一项具有开放标签扩展的VMS随机临床试验表明，TRD合并MDD患者的缓解率为27%，缓解率为15.8%。大多数有反应的患者将AD反应维持了12个月。虽然这些结果很有希望，但大多数TRD-VNS受试者没有表现出AD反应。VMS也是侵入性的，而且价格昂贵，需要手术植入VNS装置。因此，事先确定哪些患者可能从迷走神经刺激中获益的能力是一个重要的问题。此外，人们对大脑如何对VNS产生AD反应知之甚少。功能成像，包括正电子发射断层扫描或PET扫描，在识别人脑中MDD和AD反应的解剖和生理相关性方面起着关键作用。我们对TRD患者的初步PET研究揭示了VNS诱导的脑活动变化，这提示了VNS的可能作用机制。我们提出一项前瞻性PET-VNS研究，检查TRD患者对VNS反应的急性、亚急性（3个月）和慢性（12-18个月）脑区域活动的变化。此外，区域大脑活动的变化将与阿尔茨海默病的结果相关。在神经生理水平上提高对VNS作用机制的理解将增强对MDD和AD反应的理论认识，可能有助于MDD治疗的发展，并可能允许提前识别最有可能从VNS获益的患者。在美国，抑郁症是导致残疾的主要原因。数百万人患有标准治疗无效的抑郁症。迷走神经刺激（VNS）是一种很有前途的治疗这些患者的新方法。这项拟议的研究将着眼于大脑对VNS治疗的反应是如何变化的。此外，该研究将研究这些大脑变化与抑郁症的变化之间的关系。

DESCRIPTION (provided by applicant): Major Depressive Disorder (MOD) is a leading cause of disability in the US. About 20% of people with MOD (~4 million Americans) fail repeated antidepressant (AD) trials, resulting in "treatment resistant depression" (TRD). Few effective treatments exist for TRD. Even electroconvulsive therapy (ECT) is less efficacious in TRD, with -68% of ECT-treated TRD patients relapsing into MDD within one year. In 2005, the US FDA granted TRD-specific indication for Vagus Nerve Stimulation (VMS). A randomized clinical trial of VMS with an open-label extension indicated a 27% response rate and a 15.8% remission rate in TRD patients with MDD. Most patients who responded maintained AD response for a 12 month period. Although these results are promising, the majority of TRD-VNS subjects did not show AD response. VMS is also invasive and expensive, requiring surgery for VNS device implantation. The ability to determine beforehand which patients are likely to benefit from VNS is therefore an important issue. Further, little is known about how the brain responds to VNS to produce AD response. Functional imaging, including Positron Emission Tomography or PET scanning, plays a key role in identifying anatomical and physiological correlates of MDD and AD response in the human brain. Our pilot PET studies of TRD patients revealed VNS-induced changes in brain activity that suggest possible mechanisms of action for VNS. We propose a prospective PET-VNS study that examines acute, subacute (3 month), and chronic (12-18 month) changes in regional brain activity in response to VNS in TRD patients. Further, regional brain activity changes will be correlated with AD outcomes. Improved understanding of VNS mechanisms of action at the neurophysiological level will enhance theoretical knowledge of MDD and AD response, may assist development of MDD treatments, and may allow for advance identification of patients most likely to benefit from VNS. Depression is a leading cause of disability in the US. Millions of people suffer from depression that does not respond to standard treatments. Vagus nerve stimulation (VNS) is a promising new treatment for these patients. The proposed study will look at how the brain changes in response to VNS treatment. Further, the study will examine how these brain changes relate to changes in depression.