MEMBRANE PHOSPHOLIPIDS ROLE IN SCHIZOPHRENIA

膜脂在信号调节中的潜在作用 传播已经被越来越多地认识到。中国的脂类研究 精神疾病尚未得到足够的重视。 磷脂和脂肪酸组成的异常 此前有报道称，精神分裂症患者中存在这种情况。许多. 然而，这些研究因临床设计不充分而存在缺陷， 诊断标准和脂类方法学。尽管 精神分裂症中是否存在这样的异常尚不清楚， 有足够的初步数据可以保证进一步 调查。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)检测红细胞磷脂调节是否存在缺陷 脱酰化和反应化过程中的代谢存在于 精神分裂症；3)研究受体刺激的水解物 血小板型肌醇磷脂。使用最新的生化和 临床方法论，我们将系统研究血脂等 血浆生化指标。红细胞和小鼠的血小板 仔细诊断的精神分裂症患者组(n=80)， 非精神分裂症对照组(n=30)，年龄- 对照组(n=50)。三个血样将会是 在不同的时间点从同一患者那里获得 抗精神病药疗程(超过14周)，5- 为期一周的洗脱期，以及为期10周的随访研究。至 确定临床上是否存在脂类改变 稳定的、无药物的精神分裂症患者，数据来自 不要在5周(或15周)的“淘汰”结束时复发 期间将与从正常和 精神控制受试者。一些患者的统计数据 而诊断特征作为可能的差异来源将 被评估。精神分裂症亚型内的差异将 被评估。为了评估氟哌啶醇引起的改变，数据 来自在5周(或15周)结束时未复发的患者 周)“淘汰”期间将与以下数据进行比较 同样的人在抗精神病药物治疗阶段结束时。 以上获得的见解将提供对 可能调节代谢的分子机制(S) 精神分裂症患者存在缺陷。势的识别 精神分裂症的分子标志物也可能有助于识别 处于这种疾病风险中的个人，这将会有显著的 对精神分裂症的遗传学研究的影响，并可能 可能用作隔离这种异类的方法 无序分成更同质的子群。

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.