NEUROBIOLOGY OF OBSESSIVE-COMPULSIVE HOARDING

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 虽然标准的诊断分类认为强迫症（OCD）是一个单一的诊断实体，它已经变得清楚，存在几个不同的症状亚型的强迫症。 强迫症的主要症状因素是：1）攻击性强迫与检查强迫; 2）对称性强迫与安排和重复强迫; 3）污染强迫与清洁强迫;和4）囤积/储蓄症状。 这些症状因子显示不同的遗传、共病和治疗反应。 但是，由于几乎所有先前的强迫症研究都将具有不同症状模式的患者分组在一起，因此尚不清楚强迫症症状因素在病理生理学方面是否彼此不同。 在20% - 42%的强迫症患者中发现的囤积/储蓄症状是一种离散的临床综合征的一部分，包括信息处理缺陷和决策困难。 它可以导致严重的残疾，并且是对强迫症标准治疗反应不良的强有力预测因素。 更好地理解强迫性囤积症的神经生物学，需要开发更有效的治疗这种综合征。 然而，尽管它的普遍发生和临床意义，迄今为止还没有研究调查人类强迫囤积症的神经生物学。 本研究团队的先导性功能性神经影像学数据表明，强迫性囤积综合征患者的扣带回前部和后部葡萄糖代谢率显著低于正常对照组和非囤积强迫症患者，扣带回代谢与强迫性囤积/储蓄症状的严重程度呈负相关。 拟议的研究的目的是确认和扩展这些初步研究结果在一个更明确的研究，更大和更均匀的样本选择前瞻性的主题，并确定结构神经解剖和神经认知异常与强迫性囤积综合征。 这项研究将比较年龄和性别匹配的24名强迫性囤积者，24名非囤积强迫症患者和24名正常对照组，使用[18 F]-氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）测量脑葡萄糖代谢，定量磁共振成像测量局部脑体积和形态，神经心理学测试测量认知缺陷，5-羟色胺再摄取抑制剂（SRI）标准化治疗前后的变化。 长期目标是在对其病理生理学更深入了解的基础上，开发更有效的治疗强迫性囤积症的方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although standard diagnostic classifications consider obsessive-compulsive disorder (OCD) to be a single diagnostic entity, it has become clear that several different symptom subtypes of OCD exist. The principal OCD symptom factors are: 1) aggressive obsessions with checking compulsions; 2) symmetry obsessions with arranging and repeating compulsions; 3) contamination obsessions with cleaning compulsions; and 4) hoarding/saving symptoms. These symptom factors show different genetic inheritance, comorbidity, and treatment response. But since virtually all prior studies of OCD have grouped patients with diverse symptom patterns together, it is not known whether OCD symptom factors differ from one another in terms of pathophysiology. Hoarding/saving symptoms, found in 20% - 42% of OCD patients, are part of a discrete clinical syndrome that includes information-processing deficits and difficulty with decision-making. It can cause severe disability and is a strong predictor of poor response to standard treatments for OCD. A better understanding of the neurobiology of compulsive hoarding is required to develop more effective treatments for this syndrome. Yet, despite its common occurrence and clinical significance, no study to date has investigated the neurobiology of obsessive-compulsive hoarding in humans. Pilot functional neuroimaging data from our research team suggest that patients with the compulsive hoarding syndrome have significantly lower rates of glucose metabolism in the anterior and posterior cingulate gyrus than normal controls and non-hoarding OCD patients, and that cingulate metabolism is negatively correlated with the severity of compulsive hoarding/saving symptoms. The objectives of the proposed research are to confirm and extend these preliminary findings in a more definitive study with a larger and more homogeneous sample of subjects selected prospectively, and also to identify structural neuroanatomical and neurocognitive abnormalities associated with the compulsive hoarding syndrome. This study will compare age- and sex-matched groups of 24 compulsive hoarders, 24 non-hoarding OCD patients, and 24 normal controls, using [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) to measure cerebral glucose metabolism, quantitative magnetic resonance imaging to measure regional brain volumes and morphology, and neuropsychological testing to measure cognitive deficits, before and after standardized treatment with a serotonin reuptake inhibitor (SRI). The long-term goal is to develop more effective treatments for compulsive hoarding, based on an improved understanding of its pathophysiology.