MOLECULAR GENETIC STUDIES OF CHILD PSYCHOPATHOLOGY

描述(改编自申请者摘要)：几年来，几年来 儿童和青少年发病障碍，包括自闭症障碍， 注意力缺陷多动障碍、强迫症和 严重的抑郁症，已经被证明有不同程度的 基因的影响。然而，没有一致的证据表明他们 可由单基因解释，或仅由遗传因素解释。近期 遗传学在分子和统计学方面的发展使 研究这类复杂的疾病是可行的。 独立科学家奖的第一个研究部分是 收集350名被仔细诊断为自闭症的受试者。自闭症 将使用诊断性面谈和自闭症诊断观察时间表 除了通过检查儿童来诊断自闭症之外 青少年心理学家和儿童青少年精神病学家。 将保持跨站点的可靠性。DNA将从这两个地方收集 先证者及其父母。传递/不平衡检验(TDT) 将用于确定候选基因座上的等位基因是否 优先传输。此外，该数据库将可用 用于复制在其他样本中发现的任何易感基因座。 在之前的一项研究中，两个基因之间的联系不平衡 注意缺陷/多动障碍与遗传标记 多巴胺转运蛋白基因已被确定。第二个研究组成部分 独立科学家发展计划的一项研究将旨在 复制初始研究，并添加结构化诊断 面试。 在与其他同事的合作下，儿童发病的基因分析 将进行重度抑郁障碍(候选基因的TDT)。一个 重点将放在收集具有可靠性和可靠性的受试者的DNA 有效的诊断为分子遗传学研究提供数据基础 儿童和青少年的精神障碍。诊断领域的咨询师 方法学和基因分析将定期与候选人会面，以 为正在进行的研究职业发展提供指导。

DESCRIPTION (Adapted from applicant's abstract): For several years, several child and adolescent onset disorders, including autistic disorder, attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and major depressive disorder, have been shown to have varying degrees of genetic influence. However, there has been no consistent evidence that they are explained by single genes, or by genetic factors alone. Recent developments in molecular and statistical aspects of genetics have made the study of such complex disorders feasible. The first research component of the independent scientist award is to collect 350 carefully diagnosed subjects with autistic disorder. The Autism Diagnostic Interview and Autism Diagnostic Observation Schedule will be used in addition to diagnosis of autistic disorder by both the examining child and adolescent psychologist and child and adolescent psychiatrist. Cross-site reliability will be maintained. DNA will be collected from both the proband and his/her parents. The transmission/disequilibrium test (TdT) will be used to determine whether alleles at candidate loci are preferentially transmitted. In addition, this data base will be available for replication of any susceptibility loci identified in other samples. In a previous study, linkage disequilibrium between attention-deficit/hyperactivity disorder and a genetic marker at the dopamine transporter locus has been identified. A second research component of the independent scientist development plan will be a study designed to replicate the initial study with addition of a structured diagnostic interview. In collaboration with other colleagues, genetic analyses of childhood onset major depressive disorder (TdT of candidate genes) will be conducted. An emphasis will be placed on collecting DNA from subjects with reliably and valid diagnoses to provide a data base for molecular genetic studies severe disorders of children and adolescents. Consultants in diagnostic methodology and genetic analysis will meet regularly with the candidate to provide guidance for ongoing research career development.