Brain Structural Variations as Potential Endophenotypes for Psychopathic Traits

描述（由申请人提供）：精神病是一种影响约2%的普通人群和约25%的刑事罪犯的临床状况，反映了正常社会互动和道德的失败。尽管越来越多的证据表明成人精神病患者的大脑结构异常，但缺乏青少年精神病特征的神经影像学发现，阻碍了对这种复杂人格特征的病因学的进一步了解。候选人的近期职业目标是发展脑结构成像和定量遗传分析方面的专业知识，以确定哪些脑形态特征构成精神病特征的候选内表型。了解与青少年精神病特征相关的脑形态变异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，并使候选人的长期职业目标成为可能，即开发独立的大型项目，利用神经影像学表型和多变量方法来研究从童年到成年的精神病和相关疾病的遗传贡献成年。为此，利用从大型纵向双胞胎项目中收集的80对青春期双胞胎的现有神经影像学、临床和行为数据，我们建议；1)利用结构磁共振成像（sMRI）和弥散张量成像（DTI）数据的复杂神经成像分析方法来表征大脑结构表型，并研究其与精神病特征（使用儿童精神病量表和反社会过程筛查装置确定）的关联；2)利用结构方程模型估计遗传和非遗传因素对形态变异的相对贡献；3)从R00阶段的大型双胞胎项目中收集额外的160对青春期双胞胎的新成像和临床数据，以确定形态变异和精神病特征之间的遗传重叠。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专业知识和神经影像学资源，包括八个教学课程，两个密集讲习班和定期每周研讨会，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的新知识，并提高进行独立纵向双胞胎项目的技能。此外，候选人将接受培训，为学术进步做准备，以促进顺利过渡到终身教职，全职助理教授，以进行拟议的R00阶段的研究。

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.