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

临床试验表明，单次注射A型肉毒杆菌毒素可导致抑郁症状的快速和持久缓解(Wollmer等人。2012年，Finzi&Rosenthal，2014，Magid等人。2014年)。最有可能的情况是，A型肉毒杆菌毒素并没有发挥特定的抗抑郁作用，而是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：通过瘫痪表达负面情绪的肌肉(mm。通常负责维持和增强这些情绪的大脑本体感觉信号被削弱(面部反馈理论)。特别是，交界性人格障碍(BPD)似乎适合这种方法，因为它们显示出过度的负面情绪(焦虑、悲伤、愤怒、厌恶)，而且大多数功能成像研究表明，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(根据德国医学法，AMG)，该试验已获得非工业资助(Asklepios ProResearch)，并获得当地伦理委员会和监管机构的批准(NCT02728778)。这项临床试验旨在研究A型肉毒毒素单一治疗女性BPD患者眉间区域的疗效和安全性，并与头面部最小针灸治疗(n=54)进行比较。(2)一项旨在确定BPD患者这种治疗的神经元基础的实验研究。本应用仅涉及整个研究的第二部分本实验研究的目的是使用以下方法确定A型肉毒毒素注射的神经机制：(1)对不同价态的情绪面孔进行分类/处理；(2)完成包含情绪和抑制干扰的抑制任务(情绪GoNoG范式)；以及(3)使用功能磁共振成像(FMRI)检测BPD患者大脑/脑干的静息状态活动。我们假设，使用A型肉毒毒素治疗眉间区域可以减少中性或模棱两可的面部表情的负面评级，并使用GoNogo范式(行为层面)改善抑制性能。在神经元水平上，我们预计在处理负面情绪面孔的过程中，杏仁核和相关脑区的激活会减少，通过躯体感觉输入的衰减改变默认模式网络中的连通性，情绪相关脑区的活动减少，以及在GoNogo范式中前额叶抑制脑区的活动增加。

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.