MEMBRANE PHOSPHOLIPIDS ROLE IN SCHIZOPHRENIA

膜脂在信号调节中的潜在作用 传播越来越受到重视。 血脂研究 精神疾病尚未得到足够的重视。 磷脂和脂肪酸组成的减少， 以前曾在精神分裂症患者中报道过。 许多 然而，这些研究由于临床设计不充分而存在缺陷， 诊断标准和脂质方法学。 虽然 精神分裂症中是否存在这种异常尚不清楚， 有足够的初步数据证明 调查事务所 因此，这项建议的主要目标是：1） 通过表征红色来评估膜结构异常 血细胞（RBC）磷脂亚类及其分子种类; 2)为了测试红细胞磷脂调节的缺陷是否 通过脱酰和再酰化过程的代谢存在于 精神分裂症;和3）研究受体刺激的水解 血小板肌醇磷脂。 使用最新的生化和 临床方法学，我们将系统地研究脂质和其他 血浆生化指标。 红细胞和血小板 仔细诊断组精神分裂症患者（n=80）， 非精神分裂症精神病对照组（n=30），年龄- 匹配的对照受试者（n=50）。 三份血液样本将被 在不同时间点从同一患者获得， 抗精神病药物治疗的过程（超过14周），5- 一周的洗脱期和一个10周的随访研究。 到 确定临床上是否存在脂质改变 稳定的“无药”精神分裂症患者， 在5周（或15周）的“洗脱期”结束时不复发 期间将与正常和 精神病对照组 一些患者的人口统计数据 和诊断特征作为差异的可能来源， 进行评估。 精神分裂症亚型之间的差异 被评价。 为了评估氟哌啶醇诱导的变化，数据 在5周（或15周）结束时未复发的患者中， 周）的“洗脱”期将与这些数据进行比较， 在精神抑制剂治疗阶段结束时的相同个体。 以上获得的见解将有助于进一步了解 可能调节代谢的分子机制 精神分裂症中存在的缺陷 查明潜在 精神分裂症的分子标记也可能有助于识别 有这种疾病风险的人，这将有显着的 精神分裂症的遗传学研究的影响，并可能 潜在地用作分离这种异质性的手段 更均匀的亚群。

The potential role of membrane lipids in the regulation of signal transmission has been increasingly recognized. Lipid research in psychiatric diseases has not yet received adequate attention. Abnormalities of phospholipid and fatty acid composition have been previously reported in patients with schizophrenia. Many of these studies, however, were flawed by inadequate clinical design, diagnostic criteria, and lipid methodology. Although the existence of such abnormalites in schizophrenia remains unclear, there are enough preliminary data to warrant further investigations. The major goals of this proposal are thus: 1) to assess membrane structural abnormalities by characterizing red blood cell (RBC) phospholipid subclasses and its molecular species; 2) to test whether a defect in regulation of RBC phospholipid metabolism by deacylation and reacylation processes is present in schizophrenia; and 3) to study the receptor-stimulated hydrolysis of platelet inositol phospholipids. Using updated biochemical and clinical methodology, we will systematically study lipid and other biochemical parameters of plasma. RBC, and platelets of a carefully diagnosed group of schizophrenic patients (n=80), of a non-schizophrenic psychiatric control group (n=30), and of age- matched control subjects (n=50). Three blood samples will be obtained from the same patient at different time points during the course of neuroleptic treatment (greater than 14 weeks), a 5- week wash-out period, and a 10-week follow-up study. To determine whether lipid alterations are present in clinically stable, "drug-free" schizophrenic patients, data from patients who do not relapse at the end of a 5-week (or 15-week) "wash-out" period will be compared to those obtained from normal and psychiatric control subjects. A number of patient demographic and diagnostic characteristics as possible sources of variance will be assessed. Differences within the schizophrenic subtypes will be evaluated. To assess the haloperidol-induced alterations, data from patients who do not relapse at the end of the 5-week (or 15- week) "wash-out" period will be compared to data from these same individuals at the end of the neuroleptic treatment phase. Insights gained above will provide further understanding of the molecular mechanism(s) which might regulate the metabolic defects present in schizophrenia. The identification of potential molecular markers for schizophrenia may also help to identify individuals at risk for this disorder, which would have significant implications for the genetic study of schizophrenia, and could potentially serve as a means for segregating this heterogeneous disorder into more homogeneous subgroups.