DOPAMINE FUNCTIONAL SUBTYPES OF SCHIZOPHRENIA

我们的目标是定义与中枢神经系统相关的精神病症状 多巴胺(DA)受体超敏。114名住院病人 与RDC会面，主要是精神分裂症或分裂情感障碍 精神分裂症将被研究。实验1将确定精神分裂症患者 表现为中枢性DA受体超敏的患者(N=66) 利用中枢调节的生长激素反应 使用DA激动剂阿朴吗啡。患者将被分成 分为三组：亚敏感、平均或超敏反应 参照性别和年龄匹配的正常对照组。疾病的流行 三名患者的个别精神症状(SADS、SANS、NHSI) 组别将被确定。试点数据表明，思维障碍是 与中枢性DA受体超敏有关。额外的飞行员 同时测量中枢DA受体活性(生长激素反应)和 同一精神分裂症患者的中枢多巴胺释放(CSF HVA)表明 DA释放与DA受体活性呈负相关。这些 临床数据支持释放介导的DA受体下调 以前在临床前研究中报道过，但据我们所知从未 在MAN中报告。目前的提议将延长这些数据。它是 假设这两种生物之间的反向关系 变量将反映在临床变量(SADS、SANS、NHSI)中。 如果特定的精神病症状群与DA受体相关 过度敏感，那么这个症状群应该反应最快， 完全依赖于作用机制是阻断DA受体的药物 (抗精神病药物)。在实验2中，精神分裂症患者(N=48)将 接受以下药物的双盲试验：1)顺-硫杂环己烷(Navane)，2) 反式硫杂环己烯-一种临床上不活跃的立体异构体，它显示出 生化图谱与活性立体异构体相似，但不结合 DA受体和安慰剂。症状缓解的时间进程 (SADS-C、SANS和NHSI)将被确定。这项研究的具体目的 就是找出反应最好精神病症状群 迅速而完全地转化为顺式硫杂环己烯。实验1和实验2应该 识别与DA相关的同一组精神病症状，即使 方法有很大的不同。

Our objective is to define those psychotic symptoms associated with central dopamine (DA) receptor supersensitivity. One hundred fourteen inpatients meeting RDC for schizophrenia, or a schizoaffective disorder, mainly schizophrenia will be studied. Experiment 1 will identify schizophrenic patients (N=66) demonstrating a central DA receptor supersensitivity employing the centrally mediated growth hormone response following administration of the DA agonist, apomorphine. Patients will be divided into three GH groups; subsensitive, average or supersensitive response in reference to a sex and age matched normal control group. The prevalence of individual psychotic symptoms (SADS, SANS, NHSI) in the three patient groups will be determined. Pilot data suggest that thought disorder is associated with central DA receptor supersensitivity. Additional pilot data concomitantly measuring central DA receptor activity (GH response) and central DA release (CSF HVA) in the same schizophrenic patient indicates an inverse relationship between DA release and DA receptor activity. These clinical data support a release mediated down regulation of DA receptors previously reported in preclinical studies, but to our knowledge never reported in man. The present proposal will extend these data. It is hypothesized that the inverse relationship between these two biologic variables will be reflected in the clinical variables (SADS, SANS, NHSI). If a particular psychotic symptom cluster is associated with DA receptor supersensitivity, then this symptom cluster should respond most rapidly and completely to medication whose mechanism of action is to block DA receptors (neuroleptics). In Experiment 2, schizophrenic patients (N=48) will receive a double-blind trial of: 1) cis-thiothixene (Navane), 2) trans-thiothixene - a clinically inactive stereoisomer which shows a similar biochemical profile as the active stereoisomer but does not bind to DA receptors and 3) placebo. The time course of symptom remission (SADS-C, SANS and NHSI) will be determined. The specific aim of this study is to identify that cluster of psychotic symptoms that responds most rapidly and completely to cis-thiothixene. Experiments 1 and 2 should identify the same cluster of DA associated psychotic symptoms even though the methods differ greatly.