Brain Phospholipid Composition in Schizophrenia

描述（由申请人提供）：红细胞和血小板的研究表明，精神分裂症是由脑中磷脂（PL）代谢和组成变化引起的细胞膜异常引起的。基于细胞膜异常的精神分裂症假说可以潜在地解释一系列发现，并且与多种神经递质系统和神经发育的异常一致。PL前体和降解产物的检查在体内31 P核磁共振（NMR）表明精神分裂症脑PL代谢的改变。这些体内NMR研究的局限性在于PL不能直接观察到，因为它们是固体样的。对于31 P在体内的NMR结果，以支持精神分裂症的膜假说，PL前体和降解产物的变化必须与PL组合物在大脑中的实际变化。在我们实验室的初步研究中，使用31 P在体外NMR，升高磷脂酰肌醇，升高磷脂酰胆碱与一个饱和和一个不饱和的侧链，并增加总PL的趋势，被发现在提取物的尸检精神分裂症的大脑（额叶皮层）相对于控制。这些结果支持PL异常发生在精神分裂症的大脑中的概念。据推测，PL组成额叶和颞叶皮质（但不是枕叶皮质），涉及精神分裂症的地区，是不同的精神分裂症患者比对照组。还假设，在体内31 P NMR检测PL前体和/或降解产物变化的情况下，PL组成也发生变化。建议测量PL组合物（有机溶剂提取物和胆汁盐溶解）和PL前体和降解产物（高氯酸提取物）在左额叶，颞叶和枕叶皮质的相同的个人（20名精神分裂症患者，20名对照，和10名精神病对照）使用31 P在体外NMR。这项研究将揭示以往PL研究在外周组织和体内有时相互矛盾的结果。它也可能为精神分裂症的膜假说的几个方面提供支持和澄清。

DESCRIPTION (provided by applicant): Studies of erythrocytes and platelets have suggested that schizophrenia arises from cell membrane abnormalities due to changes in phospholipid (PL) metabolism and composition in the brain. A hypothesis of schizophrenia based on cell membrane abnormalities can potentially explain a range of findings, and is consistent with abnormalities in multiple neurotransmitter systems and neurodevelopment. Examination of PL precursors and degradation products by in vivo 31P nuclear magnetic resonance (NMR) suggests alterations in brain PL metabolism in schizophrenia. A limitation of these in vivo NMR studies is that PLs are not observed directly because they are solid-like. For the 31 P in vivo NMR results to support strongly the membrane hypothesis of schizophrenia, changes in PL precursors and degradation products must be linked with actual changes in PL composition in the brain. In preliminary studies in our lab using 31P in vitro NMR, elevated phosphatidylinositol, elevated phosphatidylcholine with one saturated and one unsaturated side chain, and a trend toward increased total PLs, were found in extracts of postmortem schizophrenic brain (frontal cortex) relative to control. These results support the notion that PL abnormalities occur in the brain in schizophrenia. It is hypothesized that the PL compositions in frontal and temporal cortices (but not occipital cortex), regions implicated in schizophrenia, are different in schizophrenics than in controls. It is also hypothesized that, in the cases where in vivo 31 P NMR detects changes in PL precursors and/or degradation products, changes in PL composition are also occurring. It is proposed to measure both the PL composition (organic solvent extract and bile-salt solubilization) and PL precursors and degradation products (perchloric acid extract) in left frontal, temporal and occipital cortices of the same individuals (20 schizophrenics, 20 controls, and 10 psychiatric controls) using 31 P in vitro NMR. This study will shed light on the sometimes conflicting results of previous PL studies both on peripheral tissue and in vivo. It will also potentially provide support and clarification for several aspects of the membrane hypothesis of schizophrenia.