MRS IN THE SCHIZOPHRENIA SPECTRUM

精神分裂症谱系中的夫人

• 批准号: 7605344
• 负责人: Laurence J Sprung
• 金额: $ 0.61万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605344
• 关键词: Appendix; Biologic Characteristic; Biological; Cell membrane; Chemicals; Choline; Cognitive; Cognitive deficits; Complement; Computer Retrieval of Information on Scientific Projects Database; Demyelinations; Functional disorder; Funding; Genetic; Grant; Image; Impaired cognition; Impairment; Individual; Inositol; Institution; Letters; Life; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Meta-Analysis; Modality; N-acetylaspartate; Nature; Neuroglia; Neurons; Neuropsychological Tests; Phenotype; Play; Positioning Attribute; Protocols documentation; Protons; Psychotic Disorders; Relative (related person); Research; Research Personnel; Resources; Role; Schizophrenia; Schizotypal Personality Disorder; Source; Symptoms; Temporal Lobe; Thinking; Tissues; United States National Institutes of Health; White Matter Disease; Work; base; disorder control; frontal lobe; improved; in vivo; insight; interest; response; social; white matter; willingness

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Schizotypal personality disorder (SPD) is thought to represent an intermediate phenotype between schizophrenia and normals controls (NC), with some shared phenomemonological, genetic, and biological characteristics. The symptoms of SPD, though less severe, mirror those of schizophrenia, including psychotic-like symptoms, social deficits, and cognitive impairment. Because of the intermediate position of the SPD phenotype in the schizophrenia spectrum, insights into the pathophysiology of SPD may improve our understanding not only of SPD, but of schizophrenia itself. This study proposes to investigate the biological basis of SPD using proton magnetic resonance spectroscopy (1H MRS). 1H MRS is an imaging modality that measures chemical concentrations in living tissue, providing in vivo chemical-pathological information. In this study we will use 1H MRS to measure neurometabolites that have been found to be abnormal in other white matter diseases. They are of interest because of the role that white matter abnormalities have been show to play in schizophrenia. The three neurometabolites we propose to study are N-acetyl aspartate (NAA), choline compounds (CHO), and myo-inositol (MI). NAA is found exclusively in neurons , and reduced NAA is associated with axonal loss. CHO are found in cell membranes, and increased levels are thought to be related to ongoing demyelination. MI is found in glial cells , and increased MI is associated with a reactive glial response. The levels of the metabolites found will be compared to the level of cognitive deficit found on neuropsychological testing, to determine if there is a correlation. Recent MRI work done at Mount Sinai in the schizophrenic spectrum, comparing schizophrenics to subjects with SPD as well as NC, has shown that in the temporal lobe schizophrenics have reduced volumes compared to SPD subjects, who in turn have reduced volumes relative to NC. In the frontal lobe SPD subjects and NC have similar volumes, which are somewhat greater than in schizophrenics. It may be that the greater frontal volumes and relatively greater temporal volumes seen in SPD compared to schizophrenia are related to why individuals with SPD are spared the overt psychosis and more severe cognitive and social impairment seen in schizophrenia. We hope that using 1H MRS to examine these and other regions will elucidate the nature of these volumetric differences at a chemical-pathological level. This project will complement work currently underway by Drs. Davis and Friedman to use 1H MRS to study the levels of these neurometabolites in subjects with schizophrenia and NC, using an identical acquisition protocol. Drs. Davis and Friedman have indicated their willingness to pool data so that comparisons can be made among subjects with schizophrenia, SPD, and controls (please see appendix for the letter of support). Hypothesis: We hypothesize that concentrations of temporal lobe NAA (decreased NAA is associated with axonal loss) will be highest in NC and lowest in schizophrenics, with SPD subjects in between. We expect that frontal NA will be lower in schizophrenia than in SPD and NC. The level of NAA may be negatively correlated with cognitive deficit. It is highly speculative at this point to predict the levels of CHO and MI in SPD compared to NC, as it is not known if there is any active demyelination and reactive glial response in SPD.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 精神分裂型人格障碍（SPD）被认为代表了精神分裂症和正常人对照（NC）之间的中间表型，具有一些共同的现象学，遗传和生物学特征。 SPD的症状虽然不太严重，但反映了精神分裂症的症状，包括精神病症状，社会缺陷和认知障碍。 由于SPD表型在精神分裂症谱系中的中间位置，对SPD的病理生理学的见解不仅可以提高我们对SPD的理解，而且可以提高我们对精神分裂症本身的理解。 这项研究建议使用质子磁共振光谱（1H MRS）研究SPD的生物学基础。 1H MRS是一种成像方式，可测量生物组织中的化学浓度，提供体内化学病理学信息。 在这项研究中，我们将使用1H MRS来测量在其他白质疾病中发现异常的神经代谢产物。 它们引起了人们的关注，因为在精神分裂症中表现出了白质异常的作用。 我们建议研究的三种神经代谢物是N-乙酰基天冬氨酸（NAA），胆碱化合物（CHO）和肌醇（MI）。 NAA仅在神经元中发现，而降低的NAA与轴突丢失有关。 CHO在细胞膜中发现，并且水平升高被认为与持续的脱髓鞘有关。 MI在神经胶质细胞中发现，MI增加与反应性神经胶质反应有关。 发现的代谢产物水平将与神经心理学测试中发现的认知缺陷水平进行比较，以确定是否存在相关性。 与SPD受试者相比，与SPD相比，在颞叶相比，精神分裂症与SPD和NC的受试者相比，精神分裂症与SPD和NC受试者的最新MRI工作，将精神分裂症与SPD和NC的受试者进行了比较，与SPD受试者相比，颞叶精神分裂学的体积减少了。 在额叶中，SPD受试者和NC具有相似的体积，其体积比精神分裂症患者大。 与精神分裂症相比，在SPD中看到的额叶量更大和相对较大的时间体积可能与SPD患者免于明显的精神病以及在精神分裂症中看到的更严重的认知和社会障碍有关。 我们希望使用1H MRS检查这些区域和其他区域将在化学病理学层面阐明这些体积差异的性质。 该项目将补充DRS目前正在进行的工作。戴维斯（Davis）和弗里德曼（Friedman）使用相同的采集方案使用1H MRS研究精神分裂症和NC受试者中这些神经代谢物的水平。 博士。戴维斯（Davis）和弗里德曼（Friedman）表示愿意汇总数据，以便可以在精神分裂症，SPD和控件的受试者之间进行比较（请参阅附录以获取支持信）。 假设： 我们假设颞叶NaA的浓度（NAA降低与轴突丢失相关）在NC中最高，而在精神分裂症中最低，SPD受试者介于两者之间。 我们预计精神分裂症中的额叶将比SPD和NC低。 NAA的水平可能与认知不足有关。 与NC相比，在这一点上预测SPD中CHO和MI的水平是高度推测性的，因为尚不清楚SPD中是否存在任何活跃的脱髓鞘和反应性神经胶质反应。