The Genetics And Psychobiology Of Obsessive Compulsive D

本项目涉及强迫症的临床研究，主要目的是（1）强迫症和强迫症“谱系”障碍及相关障碍的家族和遗传学研究，以及（2）提高我们对强迫症发病机制的认识。强迫症是一种严重的、可遗传的疾病，终生患病率约为世界人口的2%。遗传方式知之甚少，但可能很复杂，涉及多个小到中等影响的基因座。我们的实验室在强迫症及其遗传学的研究中已经活跃了10多年，去年成为由约翰霍普金斯大学的Gerald Nestadt博士领导的强迫症多中心遗传学研究的创始地点之一。我们在NIMH IRP中的强迫症遗传研究为这个国家多地点，计划的强迫症全基因组研究提供了DNA和家庭评估数据。强迫症遗传学联盟内的所有六个地点都在使用标准化的诊断和其他确定方法。预计该联盟将在未来三年内增加300个新的受影响兄弟姐妹家庭。该样本将用于连锁和关联分析。基因型将在这个研究强迫症的研究者联盟中共享，并最终与从第二个美国联盟获得的数据相结合。此外，对强迫症先证者和强迫症相关疾病的DNA、临床特征和人格特征的探索性分析正被用于评估基因变异的候选状态，并更好地定义家族性强迫症表型。NIMH-IRP强迫症项目现已招募并完全确定了344名强迫症患者及其家庭成员（包括11对受影响的兄弟姐妹及其家庭成员以及去年评估的25个三人组）。其他家庭正处于完成方案要求的不同阶段。我们的强迫症样本和神经性厌食症样本中的5-HT 2A受体启动子多态性之间的关联，但与神经性贪食症患者的对照组无关，被发现是性二态性的，这是女性强迫症的特征，但不是男性强迫症。这项研究的继续将允许扩大强迫症先证者，受影响的兄弟姐妹对及其家庭成员的样本。这将增加识别与强迫症和相关神经精神疾病相关的染色体区域和基因的可能性。

This project involves clinical research in obsessive-compulsive disorder (OCD) primarily directed towards (1) family and genetic studies of OCD and OCD "spectrum" disorders and related disorders, and (2) enhancement of our understanding of OCD pathogenesis.OCD is a severe, heritable condition with a lifetime prevalence of about two percent of the world population. The mode of inheritance is poorly understood but is likely complex, involving multiple loci of small to moderate effect. Our laboratory has been active in studies of OCD and its genetics for over 10 years, and last year became one of the founding sites of a multi-center genetic study of OCD, led by Dr. Gerald Nestadt of Johns Hopkins University. Our OCD genetic studies in the NIMH IRP contribute DNA and family evaluation data to this national multi-site, planned genome-wide study of OCD. Standardized diagnostic and other ascertainments are being used by all six sites within the OCD genetics consortium. It is anticipated that this consortium will add 300 new families with affected sib-pairs over the next three years. This sample will be used for linkage and association analyses. Genotypes will be shared within this consortium of investigators studying OCD and will eventually be combined with data obtained from a second U.S. consortium. In addition, exploratory analyses of DNA, clinical features and personality characteristics of OCD probands and of disorders related to OCD are being used to assess the candidacy status of gene variants and to better define the familial OCD phenotype. The NIMH-IRP OCD project has now enrolled and completely ascertained 344 individuals with OCD and family members (including 11 affected sibling pairs and their family members plus 25 trios evaluated this past year). Other families are in varying stages of completing the protocol requirements. An association between a 5-HT2A receptor promoter polymorphism in both our OCD sample and an anorexia nervosa sample, but not with a comparison group of patients with bulimia nervosa, was found to be sexually dimorphic, a characteristic of women, but not men with OCD. Continuation of this study will allow expansion of a sample of OCD probands, affected sibling pairs and their family members. This should add to the likelihood of identifying chromosomal regions and genes relevant to OCD and related neuropsychiatric disorders.