Language and Risk for Schizophrenia

描述(由申请人提供)：这项R21提案是为了提供资金，以确定连接额叶和颞叶皮质的脑白质通路的结构和功能变化在遗传高危人群中是否与低风险对照组相比有显着差异，并确定这些措施是否最终可以区分那些继续有症状的人和那些没有症状的人。因此，我们假设精神分裂症的神经发育基础是涉及处理语言和相关功能的白质通路的障碍，并且这些变化将通过核磁共振检测到，与那些没有遗传风险的人相比，这些人具有明显更好的罹患疾病的遗传风险。为了验证这一假说，我们的目标是评估一大群患精神分裂症的家庭风险增加的个人(N=60)，并将他们与年龄、性别和社会阶层比例匹配的控制组(N=30)进行比较。将使用扩散张量成像协议(DTI)确定连接颞叶和额叶的区域(钩状、弧形、下纵束、枕额下束)中白质的完整性。FMRI将通过词汇判断任务直接收集上述大脑区域和通路异常激活的证据，以区分精神分裂症患者和精神分裂症高危人群与对照组。结构变化与功能变化的关联将有助于理解任何结构异常的意义。由于在遗传风险队列中，有相当多的人可能在未来某个时候患上精神分裂症，因此目前研究中确定的缺陷可能会被发现是生物标记物，在高危个体中可能会患上精神分裂症，因此对早期干预的决定很有价值。公共卫生相关性这是R21申请资金，以确定精神分裂症(N=60)的遗传高危队列，并将它们与大脑额叶和颞叶白质通路及其功能完整性缺陷的低风险对照进行比较。核磁共振扫描将在两年多的时间里进行，以确定可在未来研究中使用的大脑成像措施，以区分那些注定要患精神分裂症的人和那些在发病前不会患精神分裂症的人。

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.