Striatal D2/D3 Dopamine receptor availability in first episode schizophrenia

过去二十年进行的神经化学脑成像研究主要集中在 评价多巴胺系统，特别是纹状体D2/D3多巴胺受体。这些研究 评估未用药患者与未用药患者之间纹状体D2/D3受体可用性的差异 人口统计学匹配的对照组，并评估了纹状体的时间过程和占用程度， 第一代和第二代抗精神病药物的D2/D3受体。占用情况调查结果 研究已经产生了有价值的和一致的信息，以确定之间的关系， 血浆药物浓度和受体占有率以及症状改善的治疗窗 和副作用然而，关于纹状体D2/D3受体是否 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 因为先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， 药物治疗此外，研究之间的变异性和未能检测到差异， 患者和对照组可能与缺乏对这些变量的考虑有关，例如在治疗时的症状。 扫描、临床治疗结果和D2/D3受体多态性。项目的具体目标 目的是评估首次发作精神分裂症患者在治疗前纹状体多巴胺（D2/D3）受体的可用性， 治疗，并评估基线纹状体多巴胺（D2/D3）受体可用性 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.还将检查与多巴胺相关基因多态性的关系。65例 40名正常对照受试者将使用该孔进行正电子发射断层扫描（PET 建立多巴胺（D2/D3）受体放射性示踪剂[11 C]-雷氯必利。患者将接受抗精神病药物治疗 并将在开始治疗前进行扫描。在完成了这个项目的具体目标，独特的 将获得关于精神分裂症患者纹状体D2/D3受体可用性的数据， 开始抗精神病药物治疗以及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.