GENETIC BASIS OF CORTICAL MALFUNCTION IN SCHIZOPHRENIA

这个项目的目的是找到与精神分裂症中发现的皮质功能损伤相关的基因位点。要使用的方法是受影响的兄弟对范式。皮质功能异常似乎是慢性精神分裂症的核心特征。患者及其兄弟姐妹的皮质功能将通过功能性核磁共振、磁共振光谱学和神经心理学测试进行量化。这些方法将被纳入联动分析。仔细诊断的先证者将从我们现有的慢性精神分裂症患者人群中招募。其他先证者是通过媒体和全国精神病联盟招募的。先证者的诊断是根据以前的精神病学记录和结构化的诊断访谈建立的。兄弟姐妹同样通过结构化的面试进行评估。所有实验对象都要提供血样进行基因分析。皮质功能的评估是通过功能性MRI和神经心理测试来完成的。之所以选择这些方法，是因为我们已经知道，与正常对照相比，精神分裂症患者表现出一些异常。据推测，一些兄弟姐妹会在这些测试中显示出一个或多个异常特征，从而表明他们可能在表型上与患病的兄弟姐妹相似，即使他们（在测试时）没有证据表明完全的综合症。这项研究和遗传分析方法的独特之处在于它不使用诊断作为识别变量。这一点很重要，因为我们已经知道，基因对精神分裂症易感性的影响并不大。目前最乐观的估计是在20%到40%之间。-精神分裂症，核磁共振，磁共振-既不是人类受试者也不是人体组织

The purpose of this project is to find genetic loci linked to the impairment in cortical function found in schizophrenia. The method to be used is the affected sibling pair paradigm. Abnormalities of cortical function appear to be core features of chronic schizophrenia. Cortical function of patients and their siblings will be quantified using functional MRI, MR Spectroscopy and neuropsychological testing. These methods will be entered into the linkage analysis. Carefully diagnosed probands will recruited from our existing in patient population of persons with chronic schizophrenia. Other probands are recruited through the media and the National Alliance for the Mentally Ill. Diagnosis of probands is established from previous psychiatric records and a structured diagnostic interview. Siblings likewise are evaluated with a structured interview. All subjects give a blood sample for genetic analysis. Evaluation of cortical function is done using functional MRI and neuropsychological testing. These procedures have been chosen because it is already known that persons with schizophrenia demonstrate some abnormality compared to normal controls. It is hypothesized that some of the siblings will show one or more abnormal traits on these tests, thus suggesting that they may be phenotypically similar to their ill sibling even though they do not evidence (at the time of testing) the full blown syndrome. This study and the method of genetic analysis is unique in that it does not use diagnosis as the identifying variable. This is important because we already know that the genetic contribution to vulnerability to schizophrenia is not large. The best current estimates put it at around 20 to 40%. - Schzophrenia, MRI, MR - Neither Human Subjects nor Human Tissues