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）及其未受影响的同胞使用基于任务的功能磁共振成像，静息态功能 连接和扩散MRI方法。强迫症是一种慢性疾病，对公共卫生造成很大负担。 治疗提出了一个特殊的挑战，因为强迫症是极其异质性的， 症状可能源自不同的神经病因。研究领域标准（RDoC） 试图通过调查行为的维度成分来解决这个问题， 大脑回路。这种应用集中在感觉现象（SP）的维度症状上， 是不舒服或令人厌恶的感官体验，驱动强迫症的重复行为，包括“不仅仅是” 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，并经历了高度痛苦。不幸的是，SP没有很好地解决标准 治疗方法，这可能部分是因为他们的神经生物学机制不好 明白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 皮层、躯体感觉皮层和运动区--这些区域以前与检测 身体感觉和身体冲动-在两个不同的功能磁共振成像任务。此外，SP的严重程度更高， 与躯体感觉区域、前额叶和前额叶之间更大的静息状态功能连接有关 皮层本研究在这些有希望的初步数据的基础上，（1）研究SP的神经机制 在一个更大的强迫症队列中，显示SP严重程度的全范围;（2）在 未受影响的兄弟姐妹对于目标1，将使用感觉现象测量100名强迫症患者的SP 规模弥散和fMRI数据将在休息和fMRI任务期间采集，这些任务之前已被验证用于招募患者。 和感觉运动区。为了识别家族性风险标记，Aim 2将比较感觉现象 强迫症先证者、50名未受影响的生物学兄弟姐妹和50名无关的健康人之间的神经回路 无轴1紊乱家族史的对照组。其他分析将调查这种关系 在神经影像学测量和其他与强迫症相关的维度症状（持续性思维， 避免伤害，完美主义），与路径分析测试模型的直接和具体的途径， 这项建议调查了一个重要的和高度普遍的集群， 这些症状的神经生物学特征仍然难以捉摸。我们使用互补的神经成像技术， 全面评估SP潜在的神经回路，并探索可能有针对性的风险标志物 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.