Endophenotypes for Borderline Personality Disorder

边缘性人格障碍的内表型

• 批准号: 7243442
• 负责人: JANINE D. FLORY
• 金额: $ 16.48万
• 依托单位: QUEENS COLLEGE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7243442
• 关键词: Adult; Affect; Affective; Aggressive behavior; Alleles; Anger; Behavioral; Behavioral Medicine; Borderline Personality Disorder; Candidate Disease Gene; Clinical; Complex; Condition; DSM-IV; Data; Diagnostic; Disease; Environmental Risk Factor; Factor Analysis; Funding; Genetic; Genetic Research; Genome; Impulsivity; Individual Differences; Interview; Joints; Laboratories; Measures; Mentored Research Scientist Development Award; Modeling; Patient Self-Report; Patients; Phenotype; Preparation; Quantitative Trait Loci; Research; Sampling; Serotonin; Siblings; Standards of Weights and Measures; Structure; Task Performances; Training; Universities; Variant; Work; career; design; endophenotype; genetic epidemiology; genetic linkage analysis; genetic pedigree; medical schools; neurogenetics; neuropathology; proband; programs; psychogenetics; self reported behavior; social; trait

DESCRIPTION (provided by applicant): This Mentored Research Scientist Development Award (K01) application is designed to reorient the applicant's research career from behavioral medicine to psychiatric genetics with a focus on Borderline Personality Disorder (BPD). BPD is a complex phenotype characterized by affeetive instability, impaired social relationships and impulsivity. Progress in understanding the neurogenetics of BPD has been slowed by the fact that the disorder is clinically heterogeneous and likely shows complex inheritance, influenced by the interaction of multiple genetic and environmental factors. These conditions suggest that classic genetic approaches, such as standard affected/unaffected linkage analysis and candidate gene studies, are unlikely to be the optimal approaches for identifying genetic factors associated with the disorder. Reconceptualizing the categorical disorder into more specific, dimensional phenotypes (i.e., intermediate phenotypes) that are putatively closer to the neuropathology of the disorder might increase the likelihood of identifying genetic factors. Impulsivity and impulsive aggression have been identified as core features of the disorder. This application proposes to evaluate impulsivity as a model intermediate phenotype for BPD using a variety of measures (e.g., clinical interview, self-report, behavior in laboratory tasks) administered to a large sample of adults who are not selected for BPD; and to people who meet DSM-IV diagnostic criteria for BPD. Siblings of BPD probands and matched controls will also complete self-report measures of impulsivity, aggression, and affective instability. The candidate will complete didactic training in genetic epidemiology/psychiatric genetics and the research plan will be conducted in the context of funded, ongoing research programs at Mount Sinai School of Medicine and the University of Pittsburgh. This research will evaluate whether the structure of impulsivity is similar in normative and patient samples and which aspects of impulsivity (e.g., nonplanning, novelty seeking) are associated with aggression and behavioral task performance in the normative sample and in people with BPD. This work will also examine familial aggregation of impulsivity, aggression and affective instability in preparation for submission of a collaborative R01 application to conduct joint linkage analysis of BPD and BPD endophenotypes in extended pedigrees.

描述（由申请人提供）：本指导研究科学家发展奖（K01）申请旨在重新调整申请人的研究生涯，从行为医学转向精神遗传学，重点关注边缘性人格障碍（BPD）。 BPD 是一种复杂的表型，其特征是情感不稳定、社会关系受损和冲动。由于 BPD 具有临床异质性，并且可能表现出复杂的遗传性，受多种遗传和环境因素相互作用的影响，因此了解 BPD 神经遗传学的进展已经放缓。这些情况表明，经典的遗传方法，例如标准受影响/不受影响的连锁分析和候选基因研究，不太可能是识别与该疾病相关的遗传因素的最佳方法。将分类疾病重新概念化为更具体的维度表型（即中间表型），这些表型可能更接近该疾病的神经病理学，可能会增加识别遗传因素的可能性。冲动和冲动攻击已被确定为该疾病的核心特征。本申请建议使用多种措施（例如，临床访谈、自我报告、实验室任务中的行为）对未选择患有 BPD 的成年人进行大样本评估，将冲动性作为 BPD 的中间表型模型进行评估；以及符合 DSM-IV BPD 诊断标准的人。 BPD 先证者和匹配对照的兄弟姐妹也将完成冲动、攻击性和情感不稳定的自我报告测量。候选人将完成遗传流行病学/精神遗传学方面的教学培训，研究计划将在西奈山医学院和匹兹堡大学资助的、正在进行的研究项目的背景下进行。这项研究将评估规范样本和患者样本中的冲动结构是否相似，以及冲动的哪些方面（例如，非计划性、寻求新奇）与规范样本和边缘性人格障碍患者的攻击性和行为任务表现相关。这项工作还将检查冲动、攻击性和情感不稳定的家族聚集，为提交协作 R01 申请做准备，以对扩展谱系中的 BPD 和 BPD 内表型进行联合连锁分析。