Striatal D2/D3 Dopamine receptor availability in first episode schizophrenia

在过去二十年中进行的神经化学脑成像研究主要集中在 评估多巴胺系统，特别是纹状体D2/D3多巴胺受体。这些研究已经 未服药患者和非服药患者纹状体D2/D3受体可用性的差异 人口学匹配的对照组，并评估纹状体占用的时间进程和大小 第一代和第二代抗精神病药物的D2/D3受体。入住率的调查结果 研究已经产生了有价值的和一致的信息，关于确定 血浆药物浓度和受体占有率与症状改善的治疗窗口 以及副作用。然而，关于纹状体D2/D3受体是否存在，数据的一致性较差 与对照组相比，患者在未用药状态下的可用性是正常的或改变的，部分原因可能是 因为以前的研究主要是在以前接受过抗精神病药物治疗的患者中进行的 药物。此外，研究之间的可变性和未能检测到 患者和对照可能与缺乏对诸如症状等变量的考虑有关 扫描、临床治疗结果和D2/D3受体基因多态性。该项目的具体目标 是为了评估首发精神分裂症患者纹状体多巴胺(D2/D3)受体的可用性 治疗和评估基线纹状体多巴胺(D2/D3)受体可用性之间的关系 以及在CIDAR治疗试验中观察到的患者之间的差异，如症状反应和 副作用。与多巴胺相关基因多态的关系也将被研究。65例患者 40名正常对照受试者将使用该井进行正电子发射断层扫描(PET) 建立了多巴胺(D2/D3)受体放射性示踪剂[11C]-拉氯普利。患者将服用抗精神病药物NATVE 并将在开始治疗前进行扫描。完成了本项目的具体目标，独一无二 将获得有关精神分裂症患者纹状体D2/D3受体可用性的数据 启动抗精神病药物治疗及其与临床和遗传变量的关系。

Neurochemical brain imaging studies conducted over the past two decades have largely focused on the evaluation of the dopamine system, in particular the striatal D2/D3 dopamine receptor. These studies have evaluated differences in striatal D2/D3 receptor availability between unmedicated patients and demographically matched controls and assessed the time course and magnitude of occupancy of striatal D2/D3 receptors by first and second generation antipsychotic medications. The findings of the occupancy studies have yielded valuable and consistent information with respect to identifying relationships between plasma drug concentrations and receptor occupancy and a therapeutic window for symptom improvement and side effects. However, the data are less consistent with respect to whether striatal D2/D3 receptor availability in the unmedicated state is normal or altered in patients compared to controls, in part perhaps because prior studies were conducted largely in patients who had been previously treated with antipsychotic medications. In addition, the variability between studies and the failure to detect a difference between patients and controls may be related to a lack of consideration of such variables as symptoms at the time of scanning, clinical treatment outcome and D2/D3 receptor polymorphisms. The specific aims of the project are to evaluate striatal dopamine (D2/D3) receptor availability in first episode schizophrenia patients prior to treatment and to evaluate the association between baseline striatal dopamine (D2/D3) receptor availability and the variance observed between patients in the CIDAR treatment trial, such as symptom response and side effects. Relationship to polymorphisms in dopamine-related genes will also be examined. 65 patients and 40 normal comparison subjects will undergo a Positron Emission Tomography (PET) scan using the well established dopamine (D2/D3) receptor radiotracer [11C]-raclopride. The patients will be antipsychotic naTve and will be scanned prior to starting treatment. Having accomplished the specific aims of this project, unique data will be obtained regarding striatal D2/D3 receptor availability in patients with schizophrenia prior to initiating antipsychotic treatment and the relationship to clinical and genetic variables.