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.

这个项目的长期目标是获得更好的 了解遗传和环境因素在疾病中的作用 发育性神经精神障碍的研究 特发性疾病，抽动症综合征(TS)。研究结束 在过去的十年里，我们在理解上取得了几个显著的进步 TS及相关条件：1)表型范围更大 TS的表达，包括慢性抽搐和强迫症)；2)TS及相关 疾病比之前认为的要普遍得多； 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其 对那些受折磨的人造成的衰弱作用使这些疾病成为主要的 公共卫生问题。了解TS及其相关基因的遗传学 行为将直接造福于关心的患者 在他们的家族中反复出现；最终，澄清了 这些情况可能会阐明它们的发病机制。我们的工作发现 建议：1)TS在家庭内以某种模式传播 符合常染色体显性遗传；2)存在 TS与强迫症的病因关系；3)家庭环境 与其他相关行为的表达相关联；以及4) 特定的环境因素可能与疾病的严重程度有关 生病了。在这个项目中，我们的目标是具体研究 基因和环境在TS及相关行为中的表达。 我们计划对未受影响的儿童进行一项前瞻性研究。 为连锁研究确定的家庭，登记了大约60个 其他儿童在这些高危人群中有患TS和相关疾病的风险 密度族。这些数据将使我们有可能描述更多 这完全是TS和其他特征之间关系的本质。 这项研究还将有助于确定对人类健康至关重要的“非遗传”因素。 TS及相关疾病的发病和变异性表达。因此， 来自此前瞻性研究样本的数据将有助于确定特定的 与可变表达相关的遗传和环境因素 在TS中。此外，这些家庭中的所有成年人和青少年都将 重新评估以更新诊断信息并连续收集 表型数据的测量将被合并到后续 旨在更好地描绘遗传表型的数据分析 这些家庭。三种类型的信息将从所有 家庭成员：1)通过直接结构化收集的诊断数据 评估；2)侧重于以下领域的神经心理学数据 注意、抑制和强迫性；3)家庭测量 环境和家庭功能。这些新数据将被纳入 转化为表型分析，旨在更好地理解遗传的TS 表型分析和连锁分析旨在检验假说 该表型的一个或多个假想基因与 已知的多态基因。