Language and Risk for Schizophrenia

语言与精神分裂症的风险

基本信息

批准号：
7862347
负责人：
Lynn Eleanor DeLisi
金额：
$ 18.01万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-08 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7862347
关键词：
Age Anterior Area Autistic Disorder Biological Markers Brain Brain imaging Brain region Broca&apos s area Characteristics Chronic Schizophrenia Cognitive Comprehension Data Data Set Detection Development Diffusion Magnetic Resonance Imaging Disease Early Diagnosis Early treatment Exploratory/Developmental Grant Functional Magnetic Resonance Imaging Funding Future Genetic Genetic Risk Hearing Hippocampus (Brain)Imagery Impaired cognition Individual Inferior Inferior frontal gyrus Language Lead Left MRI Scans Magnetic Resonance Imaging Matched Group Measurement Measures Medial Modeling Onset of illness Parahippocampal Gyrus Pathogenesis Pathology Pathway interactions Patients Process Protocols documentation Psychotic Disorders Relative (related person)Reporting Research Personnel Resources Risk Risk Factors Schizophrenia Side Social Class Superior temporal gyrus Symptoms Temporal Lobe Testing Thinking Visual Cortex Wernicke Area angular gyrus base cohort design frontal lobe gray matter high risk language processing lexical model development novel public health relevance sex white matter

项目摘要

DESCRIPTION (provided by applicant): This R21 proposal is for funding to determine whether structural and functional changes in the brain white matter pathways that connect frontal and temporal cortices are significantly different in people who are at genetic high risk for developing schizophrenia compared with low risk controls and to determine whether these measures can eventually distinguish those who go on to have symptoms from those who do not. We thus hypothesize that the neurodevelopmental basis for schizophrenia is disturbance in the white matter pathways involved in processing language and related functions, and that these changes will be detectable by MRI in significantly more well individuals that are at genetic risk for developing the illness than in those who are not. In order to test this hypothesis, we aim to evaluate a large cohort of individuals (N=60) who have an increased familial risk for developing schizophrenia and compare them to an age, sex, and social class proportionally matched group of controls (N=30). The integrity of white matter in regions that connect the temporal and frontal lobes (uncinate, arcuate, inferior longitudinal, inferior occipito-frontal fasciculi) will be determined using a Diffusion Tensor Imaging Protocol (DTI). Evidence of anomalous activation within the above brain regions and pathways will be solicited directly by fMRI using a lexical decision task previously shown to differentiate people with schizophrenia and people at high-risk for schizophrenia from controls. The correlation of structural change with functional change will provide an understanding of the significance of any structural abnormalities. Since considerably more individuals in a genetically at risk cohort are likely to develop schizophrenia sometime in the future, the deficits determined to be present in this current study may be later found to be biological markers for whom among high-risk individuals are likely to develop schizophrenia and thus be valuable for decisions about early intervention. PUBLIC HEALTH RELEVANCE This is an R21 application for funding to ascertain a genetically at high-risk cohort for schizophrenia (N=60) and compare them to low-risk controls on deficits in the integrity of brain frontal and temporal lobe white matter pathways and their functioning. MRI scans will be performed over 2 years to determine brain imaging measures that can be used in future studies to distinguish those individuals who are destined to develop schizophrenia from those who do not before the onset of illness.

描述（由申请人提供）：该R21提案是用于资金来确定与额叶和颞叶皮质连接的大脑白质途径的结构和功能变化在患有遗传高风险的遗传高风险的人中是否与低风险控制相比，与低风险控制的人相比，这些措施是否与这些措施之间的症状相比，是否有症状与那些不符合那些不适合的人的症状相比，是否有显着差异。因此，我们假设精神分裂症的神经发育基础是处理语言和相关功能所涉及的白质途径的干扰，并且MRI可以检测到这些变化在明显更良好的人群中比没有的那些人相比，患疾病的遗传风险更大。为了检验这一假设，我们旨在评估大量的个体（n = 60），他们患有精神分裂症的家族风险增加，并将其与年龄，性别和社会阶层相称的对照组（n = 30）进行比较。将使用扩散张量成像方案（DTI）确定，将在连接颞叶和额叶的区域中的白质（Uncinate，Arcuate，下纵向，下枕骨下胸膜）的完整性。 FMRI将直接使用先前显示的词汇决策任务直接征求上述大脑区域和途径的异常激活的证据，这是为了区分精神分裂症的人和精神分裂症的高风险人士与对照的人。结构变化与功能变化的相关性将提供对任何结构异常的重要性的理解。由于在遗传上有更多的人可能会在将来的某个时候发展精神分裂症，因此后来发现确定存在于本研究中的赤字可能是在高风险中的生物标记物，高风险中的人可能会发展精神分裂症，因此对于早期干预而言是有价值的。公共卫生相关性这是一项R21申请，用于确定精神分裂症高风险队列（n = 60）的遗传学上的一项申请，并将其与低风险的控制对脑额和颞叶白质途径的完整性及其功能进行比较。 MRI扫描将在2年内进行，以确定可以在以后的研究中使用的大脑成像措施，以区分那些注定要发展精神分裂症的人与在疾病发作之前未做到的人。