Neurobiology of sensory phenomena in obsessive-compulsive disorder

强迫症感觉现象的神经生物学

• 批准号: 9330339
• 负责人: Emily R Stern
• 金额: $ 63.98万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-21 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9330339
• 关键词: Address; Anisotropy; Area; Behavior; Biological; Body Image; Brain; Chronic; Chronic Disease; Complex; Conscious; Data; Detection; Development; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Dimensions; Disease; Distress; Esthesia; Etiology; Exhibits; Family history of; First Degree Relative; Functional Magnetic Resonance Imaging; Future; Genetic Risk; Goals; Guide prevention; Heritability; Impairment; Individual; Insula of Reil; Measures; Modeling; Motor; Neurobiology; Obsessive-Compulsive Disorder; Pathway interactions; Patients; Pattern; Predisposition; Prefrontal Cortex; Preventive Intervention; Protocols documentation; Psychiatry; Public Health; Recruitment Activity; Research Domain Criteria; Rest; Risk Marker; Sampling; Sensory; Severities; Siblings; Skin; Somatosensory Cortex; Statistical Models; Structure; Symptoms; Techniques; Testing; Tic disorder; Work; base; biomarker identification; brain circuitry; cohort; design; disorder risk; endophenotype; experience; high risk; indexing; multimodality; neural circuit; neurobiological mechanism; neuroimaging; neuromechanism; predictive modeling; premonitory sensory phenomena; proband; relating to nervous system; repetitive behavior; sensory mechanism; somatosensory; standard care; symptom cluster; Address; Anisotropy; Area; Behavior; Biological; Body Image; Brain; Chronic; Chronic Disease; Complex; Conscious; Data; Detection; Development; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Dimensions; Disease; Distress; Esthesia; Etiology; Exhibits; Family history of; First Degree Relative; Functional Magnetic Resonance Imaging; Future; Genetic Risk; Goals; Guide prevention; Heritability; Impairment; Individual; Insula of Reil; Measures; Modeling; Motor; Neurobiology; Obsessive-Compulsive Disorder; Pathway interactions; Patients; Pattern; Predisposition; Prefrontal Cortex; Preventive Intervention; Protocols documentation; Psychiatry; Public Health; Recruitment Activity; Research Domain Criteria; Rest; Risk Marker; Sampling; Sensory; Severities; Siblings; Skin; Somatosensory Cortex; Statistical Models; Structure; Symptoms; Techniques; Testing; Tic disorder; Work; base; biomarker identification; brain circuitry; cohort; design; disorder risk; endophenotype; experience; high risk; indexing; multimodality; neural circuit; neurobiological mechanism; neuroimaging; neuromechanism; predictive modeling; premonitory sensory phenomena; proband; relating to nervous system; repetitive behavior; sensory mechanism; somatosensory; standard care; symptom cluster

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.

项目摘要 该项目研究了强迫症患者的感觉符号的神经生物学机制 强迫症（OCD）及其使用基于任务的fMRI，静止状态功能的未受影响的兄弟姐妹 连通性和扩散MRI接近。强迫症是一种慢性疾病，表现出较高的公共卫生伯恩。 治疗提出了一个特殊的挑战，因为强迫症是极其异质的，簇 可能来自区分神经病因的症状。研究领域标准（RDOC）方法 试图通过调查更紧密对齐的行为的维度组成部分来解决这个问题 带有脑电路。该应用的重点是感官现象的维度症状（SP），该症状 是不舒服或厌恶的感觉体验，可以推动强迫症重复行为，包括“不仅仅是 正确的”感觉，身体冲动和厌恶的感觉很普遍，发生在60-80％ 强迫症患者，经历了高度痛苦的经历。不幸的是，SP并未通过标准解决 治疗方法，这可能部分是因为它们的神经生物学机制不好 理解。我们的初步数据表明，强迫症患者的SP严重程度与激活有关 岛岛，体感皮层和运动区域 - 以前与检测的区域 在两个不同的fMRI任务中，身体感觉和身体冲动。此外，SP的严重程度更高 与体感区域，岛和前额叶之间更大的静息状态功能连通性有关 皮质。该项目以这些有希望的初步数据为基础，以（1）研究SP的神经机制 在较大的强迫症队列中，显示了SP严重性的全部范围，并且（2）探测农场风险标志物 未受影响的兄弟姐妹。对于AIM 1，将使用感官现象在100名OCD患者中测量SP 规模。在休息和fMRI任务中将获取扩散和fMRI数据，以前已验证以招募Insula 和感觉运动区域。为了识别家庭风险标记，AIM 2将比较感官现象 OCD问题之间的神经电路，50个未受影响的生物学兄弟姐妹和50个无关的健康 没有轴1疾病的家族史的控制。其他分析将调查关系 在神经影像措施和与强迫症相关的其他维符号之间（持久思想， 避免危害，完美主义），路径分析测试一种直接和特定途径的模型 神经影像措施sp。该提案调查了一个重要且高度普遍的集群 神经生物学仍然难以捉摸的症状。我们使用完整的神经影像技术将 全面评估SP的神经回路和可能针对的风险标记的探针 通过未来的治疗。