NEUROBIOLOGY OF OBSESSIVE-COMPULSIVE HOARDING

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 尽管标准的诊断分类认为强迫症(OCD)是一个单一的诊断实体，但很明显，强迫症存在几种不同的症状亚型。强迫症的主要症状因素是：1)对检查强迫的攻击性痴迷；2)对安排和重复强迫的对称性痴迷；3)对清洁强迫的污染强迫；以及4)囤积/储蓄症状。这些症状因素表现出不同的遗传、共病和治疗反应。但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。囤积/储蓄症状出现在20%-42%的强迫症患者中，是一种独立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，是强迫症标准治疗反应差的强烈预测指标。需要更好地理解强迫性囤积的神经生物学，才能开发出更有效的治疗这种综合症的方法。然而，尽管它的常见发生和临床意义，到目前为止还没有研究调查人类强迫症囤积的神经生物学。 来自我们研究团队的试点功能神经成像数据表明，强迫症患者的扣带回前部和后部的葡萄糖代谢率明显低于正常对照组和非囤积性强迫症患者，并且扣带回新陈代谢与强迫囤积/储蓄症状的严重程度呈负相关。这项拟议研究的目的是在一项更明确的研究中证实和扩展这些初步发现，并在前瞻性选择的更大和更均匀的受试者样本中验证和扩展这些初步发现，并确定与强迫症候群相关的结构性神经解剖学和神经认知异常。这项研究将比较24名强迫症囤积者、24名非囤积性强迫症患者和24名正常对照的年龄和性别匹配组，使用[18F]-氟代脱氧葡萄糖正电子发射断层扫描(FDG-PET)测量大脑葡萄糖代谢，定量磁共振成像测量局部脑体积和形态，神经心理测试测量认知障碍，使用5-羟色胺再摄取抑制剂(SRI)标准化治疗前后。长期目标是在对强迫性囤积症病理生理学的更好理解的基础上，开发更有效的治疗方法。

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.