Central and Peripheral Nervous System Correlates of Difficulty Discarding in Hoarding Disorder

我们对困难的潜在神经生物学机制的理解存在着严重的差距。 丢弃，囤积障碍(HD)的核心行为特征。这一差距是一个重要的问题 因为，在它被填满之前，该领域将不能准确地识别用于新治疗的机械靶点。 高清领域的发展。拟议研究的长期目标是确定困难的生物标记物。 在HD中丢弃，并开发利用这些生物标记物的治疗方法。这一点很重要，因为目前 HD的治疗只是适度有效，在所有研究中只有35%的应答率。短期内 这里的目标是确定外周(PNS)和中枢神经系统(CNS)困难的相关因素 HD患者的丢弃行为，并将其与相关的精神病理学联系起来。其基本原理是 这一目标是通过评估PNS和CNS反应以及它们对HD和 具体到难以丢弃，我们将确定有意义的基于生物标记物的干预靶点。我们会 招募40名患有原发HD的患者，40名患有焦虑症但不患有HD的临床对照组，以及40名健康人 没有精神障碍的对照组。我们将评估电皮肤，心脏和神经(EEG)的活动在 一系列与丢弃相关和情感中立(丢弃无关)的任务。我们的中心假设是 HD患者会表现出更大的心理生理唤醒和错误相关的负性 与丢弃相关的任务会比焦虑和健康的被试控制得更好。拟议的研究将继续进行 具体目标如下：1)通过比较确定PNS和CNS与丢弃难度的相关 丢弃任务和中性任务中三叉神经节和中枢神经系统的活动；2)确定两者之间的因果关系 PNS和CNS的活动和丢弃行为；3)确定PNS和CNS是否与难度相关 与其他精神病理学相比，遗弃在HD中的出现程度更高。我们的方法是创新的 因为它使用了多水平分析，并将首次检查丢弃的直接中枢神经系统效应 临床HD参与者的决策。我们对HD的神经生物学机制的关注是重要的，因为HD 是一种常见且治疗不当的疾病，拟议的研究将对生物标记物- 知情的新型治疗方法的发展。

There is a critical gap in our understanding of the underlying neurobiological mechanisms of difficulty discarding, the core behavioral feature of hoarding disorder (HD). This gap represents an important problem because, until it is filled, the field will not be able to precisely identify mechanistic targets for new treatment development in HD. The long-term goal of the proposed research is to identify biomarkers of difficulty discarding in HD and to develop treatments that engage those biomarkers. This is important because current treatments for HD are only modestly effective, with only a 35% response rate across studies. The short-term goal here is to determine the peripheral (PNS) and central nervous system (CNS) correlates of difficulty discarding behavior in HD and to distinguish these correlates from related psychopathology. The rationale for this goal is that by assessing PNS and CNS responses and the degree to which they are unique to HD and specifically to difficulty discarding, we will identify meaningful biomarker-based intervention targets. We will recruit 40 patients with primary HD, 40 clinical controls with anxiety disorders but not HD, and 40 healthy controls without psychiatric disorders. We will assess electrodermal, cardiac, and neural (EEG) activity during a series of discarding-relevant and emotionally neutral (discarding-irrelevant) tasks. Our central hypothesis is that patients with HD will demonstrate greater psychophysiological arousal and error related negativity during the discarding-relevant task than will anxious and healthy control participants. The proposed study will pursue the following specific aims: 1) determine the PNS and CNS correlates of difficulty discarding by comparing PNS and CNS activity during the discarding and neutral tasks; 2) determine the causal relationship between PNS and CNS activity and discarding behavior; and 3) determine whether PNS and CNS correlates of difficulty discarding are present to a greater degree in HD relative to other psychopathology. Our approach is innovative because it uses multilevel analysis and will examine, for the first time, the immediate CNS effects of discarding decisions in clinical HD participants. Our focus on the neurobiological mechanisms of HD is significant, as HD is a common and poorly treated condition and the proposed study will have direct implications for biomarker- informed novel treatment development.