A Genetically Informed Study of Acute Threat Endophenotypes for Callous-Unemotional Traits

冷酷无情特征的急性威胁内表型的遗传学研究

• 批准号: 9326634
• 负责人: Ashlee Ann Moore
• 金额: $ 4.4万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-10 至 2019-05-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9326634
• 关键词: Accounting; Acute; Address; Adolescence; Adolescent; Adult; Affect; Age; Amygdaloid structure; Anterior; Antisocial Personality Disorder; Behavior; Biometry; Blinking; Characteristics; Childhood; Complex; Conduct Disorder; Data; Development; Diagnosis; Diagnostic and Statistical Manual of Mental Disorders; Dominant Genetic Conditions; Electromyography; Emotions; Empathy; Environment; Environmental Risk Factor; Equation; Etiology; Face; Female; Fright; Future; General Population; Genetic; Genetic Models; Genetic Predisposition to Disease; Heritability; Individual; Intervention; Knowledge; Legal; Literature; Measures; Mental disorders; Modeling; National Institute of Mental Health; Negative Valence; Neuroanatomy; Outcome; Patient Self-Report; Phase; Phenotype; Physiological; Physiology; Premature Mortality; Prevalence; Psychopath; Psychopathology; Reflex action; Research; Research Domain Criteria; Risk; Sampling; Strategic Planning; Structure; Training; Twin Multiple Birth; Twin Studies; Variant; base; callous unemotional trait; cingulate cortex; cost; critical developmental period; emerging adult; endophenotype; gray matter; interest; male; meetings; middle childhood; neuroimaging; physical conditioning; psychopathic personality; response; sex; skills; social; trait; violent crime; young adult

PROJECT SUMMARY Callous-unemotional (CU) traits predict socially debilitating outcomes including Antisocial Personality Disorder (ASPD) and violent crime in adulthood. Despite significant research, the etiology of CU traits is not well understood. The current project incorporates genetic, physiological, neuroanatomical and self-report measures to investigate the etiology of CU traits within the National Institute of Mental Health's (NIMH) Research Domain Criteria (RDoC). Psychopathic/CU traits have long been proposed to reflect an underlying fear-deficit, and therefore this project focuses on measures corresponding with the acute fear construct within the RDoC matrix. Specifically, the physiological measures of facial eyeblink EMG in response to startle and fear-potentiated startle probes, as well as the neuroanatomical volumetric measures of regions of interest (ROIs; anterior cingulate cortex, orbitofrontal cortex, posterior cingulate cortex and amygdala) will be investigated as potential endophenotypes for CU traits. To be considered a putative endophenotype for CU traits a measure must display three characteristics: 1) association with CU traits, 2) heritability, and 3) genetic covariation with CU traits. While startle and neuroanatomy have been shown to meet the first two criteria, little to no research has investigated the third criteria. We hypothesize that startle response and neuroanatomical ROIs will meet all three criteria for endophenotypes of CU traits. Furthermore, we hypothesize that there are specific developmental periods that are most salient for the genetic and environmental factors influencing the progression of CU traits. We will address these hypotheses through the following Specific Aims: 1) investigate the phenotypic relationship between CU traits and startle, 2) examine the genetic influence on the variation and covariation of CU traits and startle throughout childhood and adolescence, and 3) investigate potential neuroanatomical ROIs associated with CU traits, and the genetic influence on the variation and covariation of ROIs and CU traits. We will accomplish these aims using a large, genetically informative, general population sample of juvenile (ages 9-20) twins (N=1696, 848 twin pairs). Biometrical structural equation modeling (i.e., `twin modeling') will be used to decompose the variance and covariance of CU traits and potential endophenotypes proposed here into latent factors reflecting the effects of 1) additive genetics, 2) unique environment and 3) dominant genetic or shared environment. Additionally, how these influences change over the important developmental period of childhood and adolescence also will be examined. This proposal directly corresponds with the NIMH strategic plan for research, which emphasizes the need for research on 1) defining the mechanisms associated with complex behaviors and 2) determining the developmental trajectories of mental illness. The results from this study have the potential to a) confirm the use of specific measures as endophenotypes in future research on CU traits, and b) inform future developmentally-based intervention strategies.

项目摘要 无情-无情感（CU）特质预测社会衰弱的结果，包括反社会人格障碍 （ASPD）和成年后的暴力犯罪。尽管有大量的研究，CU性状的病因并不好 明白目前的项目结合了遗传、生理、神经解剖和自我报告的措施 在国家精神卫生研究所（NIMH）的研究领域内调查CU特征的病因学 标准（RDoC）。长期以来，精神病/CU特征被认为反映了潜在的恐惧缺陷， 因此，本项目的重点是与RDoC矩阵中的急性恐惧结构相对应的措施。 具体来说，面部眨眼肌电图的生理措施，以应对惊吓和恐惧增强 惊吓探针，以及感兴趣区域（ROI;前部）的神经解剖体积测量 扣带皮层、眶额皮层、后扣带皮层和杏仁核）将作为潜在的 CU性状的内表型。要被认为是CU性状的假定内表型， 表现出三个特征：1）与CU性状的关联，2）遗传力，3）与CU的遗传协变 性状虽然惊吓和神经解剖学已经被证明符合前两个标准，但很少有研究表明， 研究了第三个标准。我们假设惊吓反应和神经解剖学ROI将满足所有 CU性状内表型的三个标准。此外，我们假设有特定的 发育时期是最显着的遗传和环境因素的影响， CU性状的进展。我们将通过以下具体目标来解决这些假设：1）调查 CU性状与惊跳的表型关系，2）研究变异的遗传影响， CU性状的协变和整个童年和青春期的惊吓，以及3）调查潜在的 与CU性状相关的神经解剖学ROI，以及对CU性状的变异和协变的遗传影响。 ROI和CU特征。我们将使用大量的、遗传信息丰富的普通人群来实现这些目标 青少年（9-20岁）双胞胎样本（N=1696，848对双胞胎）。生物统计结构方程建模（即， “孪生模型”）将用于分解CU性状和潜力的方差和协方差 内表型这里提出的潜在因素反映1）加性遗传学的影响，2）独特的 3）显性遗传或共享环境。此外，这些影响如何改变 此外，亦会探讨儿童及青少年的重要发展阶段。该提案直接 与NIMH的研究战略计划相一致，该计划强调研究以下方面的必要性：1）定义 与复杂行为相关的机制; 2）确定 精神疾病这项研究的结果有可能a）确认使用特定措施， 内表型在未来的研究CU性状，和B）通知未来的发展为基础的干预 战略布局