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，精神分裂症是由于大脑中磷脂（PL）代谢和成分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相一致。通过体内31P核磁共振（NMR）检测PL前体和降解产物提示精神分裂症患者脑PL代谢的改变。这些体内核磁共振研究的一个局限性是，PLs不能直接观察到，因为它们是固体状的。为了使31p体内核磁共振结果有力地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大脑中PL组成的实际变化联系起来。在我们实验室使用31P体外核磁共振进行的初步研究中，相对于对照组，在死后精神分裂症大脑（额叶皮质）的提取物中发现了磷脂酰肌醇升高，磷脂酰胆碱具有一个饱和和一个不饱和侧链升高，以及总PLs增加的趋势。这些结果支持了精神分裂症患者大脑中出现PL异常的观点。据推测，与精神分裂症有关的额叶和颞叶皮层（但不包括枕叶皮层）的PL成分在精神分裂症患者中与对照组不同。还假设，在体内31 - P NMR检测到PL前体和/或降解产物变化的情况下，PL组成也发生了变化。本研究拟采用体外核磁共振（NMR） 31p测定同一个体（20名精神分裂症患者、20名对照组和10名精神病对照组）左额叶、颞叶和枕叶皮层的聚乳酸组成（有机溶剂提取物和胆盐增溶）以及聚乳酸前体和降解产物（高氯酸提取物）。这项研究将阐明以前在外周组织和体内的PL研究有时相互矛盾的结果。它还将潜在地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.