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: 3383901
• 负责人: ADRIANNE REVELEY
• 金额: $ 16.59万
• 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/3383901
• 关键词: biomarker; disease /disorder classification; family genetics; 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; smooth pursuit eye movement; 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，以及 (b) 减少异质性 精神分裂症的基础上区分表型亚组 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，首先通过推导 具有最高遗传性的精神分裂症的临床定义 使用 MZ:DZ 在连续一系列精神分裂症双胞胎中的有效性 比率。这样的定义在其他遗传研究中将很有价值 例如那些在多重精神分裂症家族中使用连锁标记的人。在 此外，对非精神分裂症同卵双胞胎的研究将使我们能够推断 精神分裂症与亚临床遗传外显率的临床关联。 该研究的第二个目的是调查生物相关性 同一系列的同卵双胞胎和同卵双胞胎中的精神分裂症，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学影响。由于更多的是 了解精神分裂症的遗传基础，因此重要性 定义高遗传风险的变异与那些非遗传风险的变异 不会增加其亲缘关系的风险。 研究设计：该提案基于孪生方法，使用 Maudsley Twin Register，无与伦比的临床资源，涵盖 2000 多名精神病患者 过去40年来连续确定的先证者。临床数据 双胞胎存储在遗传学部分，更新为莫兹利案例说明 已更新，先证者和同卵双胞胎可追溯到他们当前的地址： 定期间隔。因此，临床材料已可用于研究 令人印象深刻。最近确定的 120 对队列 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，这些范式要么涉及 在病因学上或被提议作为精神分裂症的生物标志物。这些都是 主要精神疾病家族史、运动偏侧性、 神经系统异常（“软”体征和中枢神经系统疾病）轻微 身体异常、复杂的连续表现和流畅的追眼 动作。还将记录医疗和产科病史。