TOURETTE'S SYNDROME & RELATED DISORDERS: STUDY OF HIGH DENSITY FAMILIES

抽动秽语综合征

• 批准号: 6579412
• 负责人: DAVID L PAULS
• 金额: $ 20.59万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6579412
• 关键词: Tourette's syndrome; adolescence (12-20); adult human (21+); behavioral /social science research tag; child psychology; clinical research; cognition; disease /disorder onset; family genetics; gene environment interaction; gene expression; genetic susceptibility; human subject; interview; linkage mapping; longitudinal human study; mental disorder diagnosis; middle childhood (6-11); obsessive compulsive disorder; pathologic process; perinatal; phenotype; preschool child (1-5); psychometrics

The long term objective of this project is to obtain a better understanding of the role of genetic and environmental factors in developmental neuropsychiatric disorders through the study of the specific disorder, Gilles de la Tourette's syndrome (TS). Research over the last decade has led to several notable advances in our understanding of TS and related conditions: 1) there is a greater range of phenotypic expression for TS including chronic tics and OCD); 2) TS and related disorders are much more common than had previously been thought; and 3) the syndrome appears to be transmitted as an autosomal dominant trait. Furthermore,the prevalence of TS and associated illnesses and their debilitating effects on those afflicted makes these conditions a major public health problem. Understanding the genetics of TS and associated behaviors will be of direct benefit to patients concerned about recurrence in their families; ultimately, clarifying the genetics of these conditions may elucidate their pathogenesis. Findings from our work suggest: 1) that TS is transmitted within families in a pattern consistent with autosomal dominant inheritance; 2) that there is an etiologic relationship between TS and OCD; 3) that family environment is associated with the expression of other associated behaviors; and 4) that specific environmental factors may be related to the severity of the illness. In this Project, we aim to examine specifically the role of genes and environment in the expression of TS and associated behaviors. We plan to conduct a prospective study of young unaffected children in families ascertained for linkage studies, enrolling approximately 60 additional children at risk to TS and associated conditions in these high density families. These data will make it possible to characterize more completely the nature of the relationship between TS and other traits. This study will also help to identify "non-genetic" factors important for the onset and variable expressions of TS and related disorders. Thus, data from this prospective study sample will help identify specific genetic and environmental factors associated with the variable expression of TS. In addition, all adults and adolescents in these families will be re-evaluated to update diagnostic information and to collect continuous measures of phenotypic data that will be incorporated into subsequent data analyses designed to delineate better the inherited phenotype in these families. Three types of information will be obtained from all family members: 1) diagnostic data collected via direct structured assessments; 2) neuropsychological data focusing on the domains of attention, inhibition, and compulsivity; and 3) measures of home environment and family functioning. These new data will be incorporated into phenotypic analyses designed to understand better the inherited TS phenotype as well as linkage analyses designed to examine hypotheses of genetic linkage of a hypothetical gene or genes for this phenotype to known polymorphic makers.

该项目的长期目标是获得更好的 了解遗传和环境因素在 通过研究 特异性疾病，吉尔·德拉特雷特综合症（TS）。研究 在过去的十年中，我们的理解取得了一些显着的进步 TS和相关条件：1）表型范围更大 包括慢性抽动和强迫症在内的TS的表达； 2）TS和相关 疾病比以前认为的更为普遍。 3） 该综合征似乎是作为常染色体显性特征传播的。 此外，TS和相关疾病的患病率及 对受苦的人的衰弱影响使这些情况成为主要 公共卫生问题。了解TS和相关的遗传学 行为将对关注的患者有直接的好处 家人的复发；最终，澄清了 这些条件可能会阐明其发病机理。我们工作的发现 建议：1）TS在家庭内部以一种模式传播 与常染色体显性继承一致； 2）有一个 TS和强迫症之间的病因学关系； 3）家庭环境是 与其他相关行为的表达相关； 4） 特定的环境因素可能与 疾病。在这个项目中，我们旨在特别研究 TS和相关行为的表达中的基因和环境。 我们计划对未受影响的年轻儿童进行前瞻性研究 家庭确定了连锁研究，大约有60个 在这些较高的情况下，有其他面临TS和相关状况的儿童 密度家庭。这些数据将使表征更多 完全是TS与其他特征之间关系的性质。 这项研究还将有助于确定“非遗传”因素对 TS和相关疾病的发作和变量表达。因此， 该前瞻性研究样本的数据将有助于确定特定 与变量表达相关的遗传和环境因素 TS。此外，这些家庭中的所有成年人和青少年将是 重新评估以更新诊断信息并收集连续的信息 表型数据的度量将纳入随后的 旨在更好地描绘出遗传表型的数据分析 这些家庭。将从所有人获得三种类型的信息 家庭成员：1）通过直接结构化收集的诊断数据 评估； 2）关注领域的神经心理学数据 注意，抑制和强迫性； 3）房屋量度 环境和家庭功能。这些新数据将合并 进行表型分析，旨在更好地理解遗传的TS 表型以及旨在检查假设的连锁分析 假设基因或该表型基因的遗传连锁 已知的多态性制造商。