Imaging the Serotonin System in Obsessive-Compulsive Disorder

强迫症中血清素系统的成像

• 批准号: 7147872
• 负责人: HELEN BLAIR SIMPSON
• 金额: $ 37.65万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-27 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7147872
• 关键词: behavioral /social science research tag; brain mapping; clinical research; frontal lobe /cortex; gamma aminobutyrate; human subject; mental disorder chemotherapy; neuroimaging; obsessive compulsive disorder; positron emission tomography; psychopathology; psychopharmacology; radiotracer; receptor binding; serotonin inhibitor; serotonin receptor; serotonin transporter

DESCRIPTION (provided by applicant): Obsessive-compulsive disorder is a prevalent, chronic, and disabling disorder. Functional brain imaging studies suggest that OCD results from a malfunctioning brain circuit that includes the orbitofrontal cortex (OFC), the caudate nucleus, and the thalamus. Because the only medications known to reduce OCD symptoms are serotonin reuptake inhibitors (SRIs), it has been hypothesized that OCD is caused by an abnormality in the brain serotonin (5-HT) system. However, it remains unclear whether SRIs reduce OCD symptoms by correcting 5-HT dysfunction or by enhancing 5-HT modulation of brain circuits whose underlying dysfunction is unrelated to 5-HT. The 5-HT hypothesis of OCD remains largely untested, in part because it has been historically difficult to examine directly the 5-HT system in the living human brain. Advances in neuroreceptor imaging techniques now permit visualization of brain neurochemistry in humans using positron emission tomography (PET) and specific radioligands. Using this technology, Dr. Blair Simpson, the Principal Investigator, has worked with Dr. Marc Laruelle, a Co-investigator, to image different aspects of the brain 5-HT system in OCD subjects. Preliminary data suggest that OCD is associated with decreased availability of one type of receptor, the 5-HT2A receptor, in the OFC; however, these exciting preliminary findings require confirmation in a larger sample. The specific aim of this RO1 application is to quantify the regional distribution of 5-HT2A receptors in 24 patients with OCD and 24 matched controls using PET and a specific radioligand for 5-HT2A receptors ([1 lC]MDL 100907). If this study confirms that OCD is associated with decreased 5-HT2A receptor availability in the OFC, these data would provide direct evidence for altered 5-HT transmission in OCD and point for the first time to a postsynaptic abnormality in the OFC. Data from this study will advance our understanding of the brain mechanisms of OCD and help build a neurobiological foundation for the development of better treatments for this disabling condition.

描述（由申请人提供）：强迫症是一种流行的慢性致残性疾病。功能性脑成像研究表明，强迫症是由包括眶额皮质（OFC）、尾状核和丘脑在内的脑回路故障引起的。因为已知唯一能减轻强迫症症状的药物是血清素再摄取抑制剂（SRI），所以有人假设强迫症是由大脑血清素（5-HT）系统异常引起的。然而，目前尚不清楚SRI是否通过纠正5-HT功能障碍或通过增强5-HT对脑回路的调节来减轻强迫症症状，而脑回路的潜在功能障碍与5-HT无关。强迫症的5-羟色胺假说在很大程度上尚未得到验证，部分原因是历史上很难直接检查活体人脑中的5-羟色胺系统。神经受体成像技术的进步现在允许使用正电子发射断层扫描（PET）和特定的放射性配体可视化人脑神经化学。利用这项技术，首席研究员Blair Simpson博士与合作研究员Marc Laruelle博士合作，对强迫症受试者大脑5-HT系统的不同方面进行成像。初步数据表明，强迫症与OFC中一种类型的受体（5-HT 2A受体）的可用性降低有关;然而，这些令人兴奋的初步发现需要在更大的样本中得到证实。该RO 1应用的具体目的是使用PET和5-HT 2A受体的特异性放射性配体（[11 C]MDL 100907）定量24名OCD患者和24名匹配对照中5-HT 2A受体的区域分布。如果这项研究证实强迫症与眶额皮层5-HT 2A受体可用性降低有关，这些数据将为强迫症中5-HT传递改变提供直接证据，并首次指出眶额皮层突触后异常。这项研究的数据将促进我们对强迫症大脑机制的理解，并帮助建立神经生物学基础，以开发更好的治疗方法。