A TWIN STUDY OF NOSOLOGY AND AETIOLOGY IN SCHIZOPHRENIA

精神分裂症疾病分类学和病因学的双胞胎研究

• 批准号: 3383900
• 负责人: ADRIANNE REVELEY
• 金额: $ 13.93万
• 依托单位: UNIVERSITY OF LONDON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3383900
• 关键词: biomarker; disease /disorder classification; eye movements; gene expression; heterozygote; human population genetics; human subject; interview; linkage mapping; mental disorder diagnosis; molecular pathology; mood disorders; nervous system disorder; patient /disease registry; psychomotor function; schizophrenia; socioenvironment; twin /multiplet

The Objectives of the project are (a) to arrive at a genetically driven clinical definition of schizophrenia, and (b) to reduce heterogeneity in schizophrenia by distinguishing phenotypic subgroups on the basis of careful diagnosis and assessment of biological correlates in MZ and DZ twins. The Specific Aims directly relate to the objectives, firstly by deriving the clinical definition of schizophrenia that has the highest genetic validity in a consecutive series of schizophrenic twins, using the MZ:DZ ratio. Such a definition will be of value in other genetic investigations such as those using linkage markers in multiplex schizophrenic families. In addition, study of the nonschizophrenic MZ co-twins will allow us to infer clinical co"elates for schizophrenia with subclinical genetic penetrance. The second aim of the study is to investigate biological correlates of schizophrenia in the same series of MZ and DZ twins, relating these to diagnosis and twin concordance in order to identify homogenous subgroups with varying genetic and other aetiological influences. As more is understood about the genetic basis of schizophrenia, so the importance of defining variants at high genetic risk vs. those non-genetic variants who do not confer risk on their biological relatives increases. Study Design: the proposal is based on the twin method, using the Maudsley Twin Register, an unparalled clinical resource of over 2000 mentally ill probands consecutively ascertained over the last 40 years. Clinical data on twins is stored in the Genetics Section, updated as the Maudsley casenotes are updated, and probands and co-twins traced to their current address at regular intervals. Thus the clinical material already available for study is impressive. The most recently ascertained cohort of 120 pairs of schizophrenic twins will be interviewed using the CASH clinical interview, and assessed using a series of paradigms which have either been implicated in aetiology or proposed as biological markers for schizophrenia. These are family history of major psychiatric disorder, motor laterality, neurological abnormality (both "soft" signs and named CNS disorders) minor physical anomaly, complex continuous performance and smooth pursuit eye movements. Medical and obstetric histories will also be noted.

该项目的目标是：（a）实现基因驱动的 精神分裂症的临床定义，和（B）减少精神分裂症的异质性， 精神分裂症通过区分表型亚组的基础上 仔细诊断和评估MZ和DZ的生物学相关性 双胞胎 具体目标与目标直接相关，首先是通过推导 精神分裂症的临床定义， 使用MZ：DZ在连续系列的精神分裂症双胞胎中的有效性 比例这样的定义将在其他遗传学研究中具有价值 例如在多重精神分裂症家族中使用连锁标记的那些。在 此外，对非精神分裂症MZ双胞胎的研究将使我们能够推断出 精神分裂症与亚临床遗传多态性的临床相关性。 本研究的第二个目的是调查 精神分裂症在同一系列的MZ和DZ双胞胎，将这些与 诊断和双胞胎一致性，以确定同质亚组 具有不同的遗传和其他病因影响。因为更多的是 了解精神分裂症的遗传基础，因此， 定义高遗传风险的变异与那些非遗传变异， 不会增加其生物学亲属的风险。 研究设计：该方案是基于双胞胎方法，使用莫兹利 Twin Register是一个无与伦比的临床资源，超过2000名精神病患者 在过去40年中连续确定的先证者。的临床数据 双胞胎被保存在遗传学部分，更新为Maudsley病例记录 更新，先证者和双胞胎追踪到他们目前的地址， 有规律的间隔。因此，临床材料已可用于研究 令人印象深刻最近确定的120对 精神分裂症双胞胎将使用CASH临床访谈进行访谈， 并使用一系列范式进行评估，这些范式要么与 或被认为是精神分裂症的生物标志物。这些是 有严重精神障碍家族史，运动偏侧， 轻度神经系统异常（“软”体征和命名的CNS疾病） 物理异常、复杂的连续性能和平滑的追踪眼 动作还将记录病史和产科史。