Brain Structural Variations as Potential Endophenotypes for Psychopathic Traits

项目摘要/摘要 精神病是一种临床疾病，影响大约2%的普通人群，约25%的人 刑事罪犯，反映了正常社会交往和道德的失败。尽管有越来越多的证据 在成年精神病患者中显示大脑结构异常，精神病患者缺乏神经影像表现 青少年的性格特征阻碍了对这种复杂人格的病因的进一步理解 特征。应聘者的直接职业目标是发展结构脑成像和 定量遗传分析，以确定哪些脑形态特征可作为候选 精神变态特征的内在表型。了解脑形态的遗传贡献 与青少年精神变态特征有关的变化将为严格的 检查精神病态特征的遗传易感性，并使候选人的长期 使用神经成像表型和多变量开发独立大型项目的职业目标 方法调查儿童时期精神病及相关疾病的遗传因素。 成人期。为此，使用现有的80名青少年的神经成像、临床和行为数据 从一个更大的纵向双胞胎项目中收集的双胞胎，我们建议：1)使用几个复杂的 神经成像分析方法在结构磁共振成像和扩散张量中的应用 成像(DTI)数据以表征脑结构表型并检查其与 精神病态特征(使用儿童精神病态量表和反社会过程筛查进行鉴定 2)使用结构方程模型估计遗传和非遗传的相对贡献 与形态变异有关的因素；以及3)收集另外160例患者的新的成像和临床数据 来自R00阶段较大双胞胎项目的青春期双胞胎确定 形态变异和精神变态特征。候选人的正式训练将占富人的便宜 加州大学洛杉矶分校和南加州大学的遗传专业知识和神经成像资源，将包括八门教学课程，两门 强化工作坊和每周定期研讨会，旨在增强应聘者以前的经验 图像分析方法，培养行为遗传分析和儿童精神变态的新知识，以及 提升进行独立纵向孪生项目的技能。此外，候选人还将收到 为升学做准备的培训，以促进顺利过渡到终身教职轨道， 建议的R00阶段研究的全职助理教授职位。

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.