Novel approaches to the investigation of psychobiological mechanisms in functional neurological disorder

功能性（分离性）神经症状障碍（FND）定义为令人痛苦和致残的身体症状（例如，癫痫发作、震颤、瘫痪），而不是由已知的神经损伤或疾病引起的。患有FND的人在日常功能方面有困难（例如，工作、人际关系）和生活满意度降低。FND还与耻辱和获得治疗的障碍有关，部分原因是FND的原因还没有得到很好的理解，患者经常“通过身体和精神健康服务之间的差距”。FND患者报告创伤和压力性生活事件的发生率更高，挑战性的人际关系和一系列心理健康症状（例如，抑郁症，焦虑症），与普通人群相比（Brown & Rumber，2016; Ludwig et al.，2019; Pick等人，2016年; 2017年）。研究表明，患有FND的人在识别和调节情绪方面遇到困难，可能对压力源有更强的身体反应，但往往没有意识到这一点（Pick等人，2016年; 2017年; 2018年; 2019年）。然而，目前还不清楚这些心理因素如何导致FND症状，也不清楚它们如何与一些脑扫描研究中报告的细微异常相关。需要更多的研究来探索这些心理因素的相关性，以及它们如何与FND的症状和其他生物学特征相关。在研究证据的基础上，我最近提出，更强烈的情绪反应可能引发或恶化FND症状，因为更大的身体“战斗或逃跑”反应（“自主觉醒”）（Pick et al.，2019年）。这可能是由于情绪大脑系统和涉及其他重要功能的大脑区域之间的交流异常，例如运动，感觉和自我/身体意识（例如，（一个人的身体或情绪状态）。我的研究结果最近表明，一种称为“解离”的心理过程可能直接引发FND症状（Pick et al.，2017年; 2020年）。解离广义上是指一个人的经验的不同方面之间的脱节（例如，感觉与自己的情绪或外部世界分离，感觉对自己的身体控制力下降），通常是对压力经历和强烈情绪反应的反应。因此，分离可能解释情绪异常和FND症状之间的联系。拟议研究的主要目的是调查触发或恶化FND症状的因素，重点是情绪反应，自主觉醒和解离。第二个目标是评估这些过程是否与大脑功能的差异有关。患有不同类型FND的患者（即，癫痫发作或运动症状），并将其与具有常见精神健康症状（抑郁症）的人和没有显著精神或身体健康障碍的人进行比较，以检查这些群体的潜在相似性和差异。将测量各种相关特征，包括参与者的主观“当下”体验（情绪、解离）、唤醒的身体测量（例如，心率）和FND症状。将在实验室和现实生活环境中采取一些措施，以评估结果是否一致。研究结果将提供更多关于FND中生物和心理因素之间相互作用的信息，并将对改进或开发急需的新治疗方法产生重大影响。希望这项研究将为研究和治疗这种复杂疾病的更综合的方法提供基础，结合身心健康的观点。

Functional (dissociative) neurological symptom disorder (FND) is defined by distressing and disabling physical symptoms (e.g., seizures, tremor, paralysis) that are not caused by a known neurological injury or illness. People with FND have difficulties in daily functioning (e.g., work, relationships) and reduced life satisfaction. FND is also associated with stigma and barriers to accessing treatment, partly because the causes of FND are not well understood and patients often 'fall through the gaps' between physical and mental health services. It is crucial that FND is better understood scientifically, so that treatment options and outcomes improve rapidly.People with FND report higher rates of trauma and stressful life events, challenging personal relationships and a range of mental health symptoms (e.g., depression, anxiety), compared to the general population (Brown & Reuber, 2016; Ludwig et al., 2019; Pick et al., 2016; 2017). Studies have shown that people with FND experience difficulties in recognising and regulating emotions, potentially having stronger physical reactions to stressors, yet often being unaware of this (Pick et al., 2016; 2017; 2018; 2019). However, it is not well understood how these psychological factors contribute to FND symptoms, nor how they relate to subtle abnormalities reported in some brain scan studies. More research is needed to explore the relevance of these psychological factors, and how they relate to symptoms and other biological features in FND.On the basis of research evidence, I recently proposed that stronger emotional reactions could trigger or worsen FND symptoms, because of a greater physical 'fight or flight' response ('autonomic arousal') (Pick et al., 2019). This could be due to abnormalities in communication between emotional brain systems and brain areas involved in other important functions, such as movement, sensation and self/body awareness (e.g., knowledge of one's own bodily or emotional states). My findings have recently suggested that a psychological process called 'dissociation' might directly trigger FND symptoms (Pick et al., 2017; 2020). Dissociation broadly refers to a disconnection between different aspects of a person's experience (e.g., feeling detached from one's emotions or the outside world, feeling in less control over one's body) and often occurs in response to stressful experiences and strong emotional reactions. Dissociation could therefore potentially explain the connection between emotional abnormalities and FND symptoms. The primary aim of the proposed research is to investigate factors that trigger or worsen FND symptoms, with a focus on emotional responses, autonomic arousal and dissociation. A second aim is to assess whether these processes are linked to differences in brain functioning. Patients with different types of FND (i.e., seizures or movement symptoms) will be included and compared to people with common mental health symptoms (depression) and people with no significant mental or physical health disorders, to examine potential similarities and differences to these groups. A variety of relevant features will be measured, including participants' subjective 'in-the-moment' experiences (emotions, dissociation), physical measures of arousal (e.g., heart rate), and FND symptoms. Some measures will be taken in both laboratory and real-life settings, to assess whether findings are consistent. Brain structure and functioning will also be assessed in a scanner.The results of the research will provide more information about the interaction between biological and psychological factors in FND and will have considerable implications for improving or developing new treatments, which are much needed. It is hoped that the research will provide a basis for a more integrated approach to studying and treating this complex disorder, combining both physical and mental health perspectives.