Neurobiology of sensory phenomena in obsessive-compulsive disorder

项目摘要 本研究旨在探讨强迫症患者感觉症状的神经生物学机制。 强迫症(OCD)及其未受影响的兄弟姐妹使用基于任务的功能磁共振成像，静息状态功能 连通性和扩散磁共振成像方法。强迫症是一种慢性疾病，对公共卫生造成很大负担。 治疗是一个特别的挑战，因为强迫症是非常不同的，有成群的 症状可能源于不同的神经病因。研究领域标准(RDoC)方法 试图通过调查行为的维度组件来解决这个问题，这些维度组件与 有脑部电路。这个应用集中在感觉现象的次元症状(SP)，它 是导致强迫症患者重复行为的不舒服或令人厌恶的感官体验，包括 正确的“感觉，身体的冲动，和厌恶的感觉。SP非常普遍，发生在60%-80%的 强迫症患者，并经历了极大的痛苦。不幸的是，标准没有很好地解决SP问题 治疗方法，这可能部分是因为它们的神经生物学机制不好 明白了。我们的初步数据表明，强迫症患者SP的严重程度与激活有关 脑岛、躯体感觉皮质和运动区--这些区域以前与检测到 身体感觉和身体冲动--在两个不同的fMRI任务中。此外，SP的严重程度更高 与躯体感觉区、脑岛和前额叶之间更强的静息状态功能连接有关 大脑皮层。本项目以这些有希望的初步数据为基础：(1)研究SP的神经机制 在一个更大的强迫症队列中显示了SP的全部严重程度和(2)在 未受影响的兄弟姐妹。对于目标1，将使用感觉现象来测量100名强迫症患者的SP 比例。弥散和fMRI数据将在REST和fMRI任务期间获得，此前已验证为招募脑岛 和感觉运动区。为了识别家族性风险标记，目标2将比较感觉现象 以及强迫症先证者、他们的50名未受影响的亲生兄弟姐妹和50名无关的健康人之间的神经回路 无1号轴系疾病家族史的对照组。其他分析将调查两者之间的关系 神经成像措施和其他与强迫症相关的维度症状之间的关系(持之以恒的思维， 危害避免、完美主义)，路径分析测试直接和特定路径的模型 对SP进行神经影像检查。这项建议调查了一个重要的和高度流行的集群 神经生物学仍难以捉摸的症状。我们使用互补的神经成像技术将 全面评估SP潜在的神经回路，并探测可能成为靶点的风险标志物 通过未来的治疗。

Project Summary This project investigates the neurobiological mechanisms of sensory symptoms in patients with obsessive- compulsive disorder (OCD) and their unaffected siblings using task-based fMRI, resting-state functional connectivity, and diffusion MRI approaches. OCD is a chronic disorder presenting a high public health burden. Treatment presents a particular challenge because OCD is extremely heterogeneous, with clusters of symptoms likely derived from differing neural etiologies. The Research Domain Criteria (RDoC) approach seeks to address this problem by investigating dimensional components of behavior that more closely align with brain circuitry. This application focuses on the dimensional symptom of sensory phenomena (SP), which are uncomfortable or aversive sensory experiences that drive repetitive behaviors in OCD, including “not just right” sensations, physical urges, and sensations of disgust. SP are very prevalent, occurring in 60-80% of OCD patients, and experienced as highly distressing. Unfortunately, SP are not well addressed by standard treatment approaches, which may be in part because their neurobiological mechanisms are not well understood. Our preliminary data indicated that severity of SP in OCD patients was associated with activation of the insula, somatosensory cortex, and motor regions – areas previously associated with the detection of body sensation and physical urges – during two different fMRI tasks. Furthermore, greater severity of SP was related to greater resting-state functional connectivity between somatosensory regions, insula, and prefrontal cortex. This project builds on these promising preliminary data to (1) investigate the neural mechanisms of SP in a larger OCD cohort showing the full range of SP severity and (2) probe for familial risk markers in unaffected siblings. For Aim 1, SP will be measured in 100 OCD patients using the Sensory Phenomena Scale. Diffusion and fMRI data will be acquired during rest and fMRI tasks previously validated to recruit insula and sensorimotor regions. In order to identify familial risk markers, Aim 2 will compare sensory phenomena and neural circuitry between OCD probands, 50 of their unaffected biological siblings, and 50 unrelated healthy controls without a family history of Axis 1 disorders. Additional analyses will investigate the relationship between neuroimaging measures and other dimensional symptoms relevant for OCD (perseverative thought, harm avoidance, perfectionism), with path analyses testing a model of direct and specific pathways from neuroimaging measures to SP. This proposal investigates a significant and highly prevalent cluster of symptoms whose neurobiology remains elusive. Our use of complementary neuroimaging techniques will comprehensively assess the neural circuitry underlying SP and probe for markers of risk that could be targeted by future treatments.