The Genetics And Psychobiology Of Obsessive Compulsive D

强迫症的遗传学和心理生物学

• 批准号: 6681060
• 负责人: DENNIS L MURPHY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6681060
• 关键词: adult human (21+); anticonvulsants; basal ganglia; behavioral genetics; brain electrical activity; combination chemotherapy; fluoxetine; gamma aminobutyrate; genetic polymorphism; genetic promoter element; hormone regulation /control mechanism; human subject; human therapy evaluation; magnetic field; magnetic resonance imaging; mental disorder chemotherapy; obsessive compulsive disorder; pathologic process; patient oriented research; psychobiology; serotonin transporter

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.

该项目涉及主要针对OCD和OCD“ Spectrum”疾病和相关疾病的家族和遗传研究的强迫症（OCD）的临床研究，以及（2）对OCD发病机理的理解增强我们对OCD的理解。OCD是一种严重的，可归因的病情，其生命周期约为世界人群的寿命约为百分之二。遗传方式尚不清楚，但可能很复杂，涉及小到中度效应的多个基因座。我们的实验室已经积极研究了OCD及其遗传学的研究已有10多年了，去年成为约翰·霍普金斯大学（Johns Hopkins University of Johns Hopkins University）杰拉尔德·内斯塔特（Gerald Nestadt）博士领导的OCD多中心遗传研究的创始场所之一。我们在NIMH IRP中的强迫症遗传研究为这项全国多站点，计划的全基因组研究的OCD贡献了DNA和家庭评估数据。 OCD遗传联盟中的所有六个地点都使用了标准化的诊断和其他确定性。预计该财团将在未来三年内增加300个新家庭，并具有受影响的同胞。该样本将用于链接和关联分析。基因型将在研究强迫症的研究人员的联盟中共享，并最终将与第二个美国联盟获得的数据相结合。此外，对DNA的探索性分析，OCD概率的临床特征和人格特征以及与OCD相关的疾病的探索性分析被用于评估基因变异的候选性状态，并更好地定义家族性OCD表型。 NIMH-IRP OCD项目现已招募并完全确定了344名患有强迫症和家人的人（包括11个受影响的兄弟姐妹对及其家人以及去年评估的25个三重奏）。其他家庭处于完成协议要求的不同阶段。在我们的强迫症样本和神经性厌食症样本中，5-HT2A受体启动子多态性之间的关联，但与比较神经性贪食症患者的比较组之间的关联是性二态性的，是女性的特征，是女性的特征，但不是男性。这项研究的延续将允许扩大OCD检验样本，受影响的兄弟姐妹对及其家人。这应该增加鉴定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。