Treatment of Borderline Personality Disorder with Botulinumtoxin A: Neuronal Foundations of Emotion Processing and Impulse Control (BTX-BPS)

临床试验表明，在眉间区域单次注射肉毒杆菌毒素A可导致抑郁症状的快速和持久缓解（Wollmer et al. 2012，Finzi & Rosenthal 2014，Magid et al. 2014）。最有可能的是，肉毒杆菌毒素A不发挥特定的抗抑郁作用，但通过中断面部反馈，导致焦虑和悲伤等负面情绪的普遍减弱：通过麻痹表达负面情绪的肌肉（mm. corrugatores supercilii和m.大脑的本体感受信号，通常负责维持和增强这些情绪，减少了（面部反馈理论）。特别是，边缘型人格障碍（BPD）似乎适合这种方法，因为他们表现出过多的负面情绪（焦虑，悲伤，愤怒，厌恶），大多数功能成像研究显示这些患者的杏仁核激活增加。整个研究由两部分组成：（1）临床随机对照试验（根据德国医药法，AMG），已获得非工业资助（Asklepios proresearch）并获得当地伦理委员会和监管机构的批准（NCT 02728778）。该临床试验的目的是研究与头面部最小针灸治疗相比，用肉毒杆菌毒素A对BPD女性患者的眉间区域进行单次治疗的有效性和安全性（n=54）。(2)一项旨在确定BPD患者这种治疗的神经基础的实验研究。本申请仅涉及整个研究的第二部分。实验研究的目的是使用以下方法识别肉毒杆菌毒素A注射的神经元机制：（1）不同效价的情绪面孔的分类/处理;（2）完成抑制任务（情绪GoNoG范式）结合情绪和抑制的干预;（3）采用功能性磁共振成像（fMRI）检测BPD患者脑/脑干的静息态活动。我们假设，治疗的眉间区域与肉毒杆菌毒素A导致较少的负面评级中性或模糊的面部表情和改善的抑制性能使用GoNogo范式（行为水平）。在神经元水平上，我们预期在处理负面情绪面孔的过程中杏仁核和相关脑区的激活减少，通过减弱体感输入和减少情绪相关脑区的活动以及增加前额叶抑制性脑区的活动，在GoNogo范式中，默认模式网络内的连接性改变。

Clinical trials have shown that a single injection with botulinum toxin A of the glabella region can lead to a rapid and long lasting alleviation of depressive symptoms (Wollmer et al. 2012, Finzi & Rosenthal 2014, Magid et al. 2014). Most probably botulinum toxin A does not exert specific antidepressant effects but leads to a general attenuation of negative emotions such as anxiety and sadness through interruption of a facial feedback: By paralysing muscles that express negative emotions (mm. corrugatores supercilii and m. procerus) proprioceptive signals to the brain, normally responsible for maintenance and enhancement of these emotions, are diminished (Facial Feedback Theory). In particular, Borderline Personality Disorders (BPD) seem appropriate for such an approach as they show an excess of negative emotions (anxiety, sadness, anger, disgust), and most of functional imaging studies show an increased activation of the amygdala in these patients. The entire study consists of two parts: (1) A clinical randomised controlled trial (according to German Medicine Law, AMG) which already received non-industrial funding (Asklepios proresearch) and approval of the local ethics committee and regulatory authorities (NCT02728778). The clinical trial aims at investigating the efficacy and safety of a single treatment of the glabella region with botulinum toxin A in female patients with BPD compared to a minimal acupuncture treatment of head and face (n=54). (2) An experimental study aiming at identifying the neuronal underpinnings of such a treatment in patients with BPD. The application refers only to this second part of the entire study Purpose of the experimental study is the identification of neuronal mechanisms of botulinum toxin A injections using the following approach: (1) classification/processing of emotional faces of different valence; (2) completion of an inhibitory task (emotional GoNoG paradigm) incorporating the interference of emotion and inhibition; and (3) resting state activity of the brain/brainstem in patients with BPD using functional magnet resonance imaging (fMRI). We hypothesize that the treatment of the glabella region with botulinum toxin A leads to less negative ratings of neutral or ambiguous facial expressions and an improved inhibitory performance using the GoNogo paradigm (behavioral level). On the neuronal levels we expect a diminished activation of the amygdala and associated brain areas during processing of negative emotional faces, an altered connectivity within the default mode network through attenuation of somatosensory input and a decreased activity of emotion related brain regions as well as increased activity of prefrontal inhibitory brain regions during the GoNogo paradigm.