Brain Structural Variations as Potential Endophenotypes for Psychopathic Traits

项目总结/摘要 精神病是一种临床病症，影响约2%的普通人群，约25%的 这反映了正常社会交往和道德的失败。尽管越来越多的证据表明 显示成年精神病患者的大脑结构异常，缺乏精神病患者的神经影像学发现， 在青少年中的性格特征阻碍了对这种复杂人格的病因学的进一步理解 性状候选人的直接职业目标是发展脑结构成像方面的专业知识， 定量遗传分析，以确定哪些脑形态学特征构成候选者 精神病特征的内在表型了解大脑形态学的遗传贡献 青少年心理变态特征的变化将为一个严格的 检查精神病特征的遗传倾向，并使候选人的长期 利用神经影像学表型和多变量开发独立的大型项目的职业目标 方法调查精神病和相关疾病的遗传贡献，从童年到 成年为此，使用80名青少年现有的神经影像学、临床和行为数据， 从一个更大的纵向双胞胎项目收集的双胞胎，我们建议; 1）使用几个复杂的 应用于结构磁共振成像（sMRI）和扩散张量的神经成像分析方法 DTI数据来表征结构脑表型，并检查它们与 精神病特征（使用儿童精神病量表和反社会过程筛查确定） 2）使用结构方程模型来估计遗传和非遗传的相对贡献 形态学变化的因素;以及3）收集额外160例患者的新成像和临床数据 青少年双胞胎从较大的双胞胎项目在R00阶段，以确定遗传重叠之间 形态变异和精神病特征候选人的正规训练会利用有钱人 遗传学专业知识和神经影像资源在加州大学洛杉矶分校和南加州大学，将包括八个教学课程，两个 密集的讲习班和每周定期的研讨会，旨在增加候选人的先前经验， 图像分析方法，培养行为遗传分析和儿童精神病方面的新知识， 促进开展独立纵向双胞胎项目的技能。此外，候选人将获得 为学术进步做准备的培训，以促进向终身教职轨道的平稳过渡， 全职助理教授职位，用于拟议的R00阶段研究。

PROJECT SUMMARY/ ABSTRACT Psychopathy is a clinical condition that affects approximately 2% of the general population, and ~25% of criminal offenders, and reflects a failure in normal social interaction and morality. Despite increasing evidence showing brain structural abnormalities in adult psychopaths, the lack of neuroimaging findings for psychopathic traits among adolescents has prevented further understanding in the etiology of such complex personality traits. The candidate's immediate career goal is to develop expertise in structural brain imaging and quantitative genetic analysis in order to identify which brain morphological characteristics pose as candidate endophenotypes for psychopathic traits. Understanding the genetic contributions of brain morphological variations in relation to psychopathic traits in adolescents will build the necessary foundation for a rigorous examination of the genetic predispositions to psychopathic traits and make possible the candidate's long-term career goal of developing independent large-scale projects using neuroimaging phenotypes and multivariate methods to investigate the genetic contributions of psychopathy and related disorders from childhood through adulthood. Towards this end, using the existing neuroimaging, clinical, and behavioral data of 80 adolescent twins collected from a larger longitudinal twin project, we propose to; 1) use several sophisticated neuroimaging analysis methods applied to structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI) data to characterize structural brain phenotypes and examine their association with psychopathic traits (identified using the Childhood Psychopathy Scale and the Antisocial Process Screening Device); 2) use structural equation modeling to estimate the relative contributions of genetic and non-genetic factors toward morphological variations; and to 3) collect new imaging and clinical data on an additional 160 adolescent twins from the larger twin project in the R00 phase to determine the genetic overlap between morphological variations and psychopathic traits. The candidate's formal training will take advantage of the rich genetic expertise and neuroimaging resources at UCLA and USC and will include eight didactic courses, two intensive workshops and regular weekly seminars designed to augment the candidate's prior experience in image analysis methods, foster new knowledge in behavioral genetic analysis and child psychopathy, and promote skills for conducting an independent longitudinal twin project. Additionally, the candidate will receive training for the preparation for academic advancement to enhance a smooth transitioning into a tenure-track, full-time assistant professorship for the proposed R00 phase research.