Vagus Nerve Stimulation for Depression: PET Studies

描述（由申请人提供）：严重抑郁症（MOD）是美国残疾的主要原因。大约20%的MOD患者（约400万美国人）反复抗抑郁药（AD）试验失败，导致“治疗抵抗性抑郁症”（TRD）。对于TRD，几乎没有有效的治疗方法。即使是电休克治疗（ECT）在TRD中也不太有效，约68%的ECT治疗的TRD患者在一年内复发为MDD。2005年，美国FDA批准了迷走神经刺激（VMS）的TRD特定适应症。一项具有开放标签扩展的VMS随机临床试验表明，MDD TRD患者的缓解率为27%，缓解率为15.8%。大多数有应答的患者维持AD应答12个月。虽然这些结果是有希望的，但大多数TRD-VNS受试者没有显示出AD应答。VMS也是侵入性的且昂贵的，需要进行VNS装置植入手术。因此，事先确定哪些患者可能从VNS中受益的能力是一个重要的问题。此外，关于大脑如何响应VNS以产生AD响应知之甚少。功能成像，包括正电子发射断层扫描或PET扫描，在识别人类大脑中MDD和AD反应的解剖学和生理学相关性方面起着关键作用。我们对TRD患者进行的初步PET研究揭示了VNS诱导的脑活动变化，提示了VNS可能的作用机制。我们提出一项前瞻性PET-VNS研究，检查TRD患者VNS引起的局部脑活动的急性、亚急性（3个月）和慢性（12-18个月）变化。此外，局部脑活动变化将与AD结果相关。在神经生理学水平上对VNS作用机制的进一步理解将增强MDD和AD反应的理论知识，可能有助于MDD治疗的开发，并可能允许提前识别最有可能从VNS中获益的患者。抑郁症是美国残疾的主要原因。数百万人患有抑郁症，对标准治疗没有反应。迷走神经刺激（VNS）是一种很有前途的新的治疗这些患者。这项拟议中的研究将着眼于大脑如何对VNS治疗作出反应。此外，该研究将研究这些大脑变化如何与抑郁症的变化相关。

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.