Brain Structural Variations as Potential Endophenotypes for Psychopathic Traits

描述（由申请人提供）：精神病是一种临床疾病，影响约2%的普通人群，约25%的刑事犯罪者，并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，在成年精神病患者的大脑结构异常，缺乏神经影像学研究结果的青少年中的精神病特征，阻止了进一步了解这种复杂的人格特征的病因。候选人的直接职业目标是发展结构脑成像和定量遗传分析方面的专业知识，以确定哪些大脑形态学特征构成精神病特征的候选内在表型。了解青少年大脑形态变异对精神病特征的遗传贡献，将为严格检查精神病特征的遗传易感性奠定必要的基础，并使候选人发展独立的大细胞的长期职业目标成为可能。使用神经影像学表型和多变量方法调查儿童期精神病和相关疾病的遗传贡献的规模项目直到成年为此，利用现有的神经影像学，临床和行为数据的80个青少年双胞胎收集了一个更大的纵向双胞胎项目，我们建议; 1）使用几种复杂的神经成像分析方法应用于结构磁共振成像（sMRI）和扩散张量成像（DTI）数据，以表征结构脑表型，并检查它们与精神病特征的关联（使用儿童期精神病量表和反社会过程筛选装置识别）; 2）使用结构方程模型来估计遗传和非遗传因素对形态变异的相对贡献;（3）在R 00阶段收集来自较大双胞胎项目的另外160名青少年双胞胎的新的成像和临床数据，以确定形态学之间的遗传重叠。变异和精神病特征候选人的正式培训将利用加州大学洛杉矶分校和南加州大学丰富的遗传学专业知识和神经影像学资源，包括八门教学课程，两个密集的研讨会和每周定期的研讨会，旨在增加候选人在图像分析方法方面的经验，培养行为遗传分析和儿童精神病方面的新知识，并促进进行独立纵向双胞胎项目的技能。此外，候选人将接受培训，为学术进步做好准备，以加强顺利过渡到终身教职，全职助理教授职位，用于拟议的R 00阶段研究。 公共卫生相关性：儿童和青少年的精神病态特征与几种成人精神疾病有关，但关于青少年精神病态特征的神经基础知之甚少。通过识别精神病特征的结构相关性，并使用青少年双胞胎样本检查形态特征的遗传力，我们可以确定精神病特征的候选内在表型。因此，这项拟议中的研究具有很大的潜力，可以确定精神病的病因相关的前兆，这反过来又对开发新的假设，治疗和预防干预至关重要。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Psychopathic traits in children and adolescents have been linked to several adult psychiatric disorders, however extremely little is known regarding the neural basis of psychopathic traits in adolescents. By identifying structural correlates of psychopathic traits and examining the heritability for morphological characteristics using an adolescent twin sample, we can determine the candidate endophenotypes for psychopathic traits. This proposed study thus has great potential for identifying etiologically relevant precursors of psychopathy, which in turn would be crucial for developing new hypothesis, treatments, and preventative interventions.