Child adversity and the developmental epidemiology of mood and anxiety disorders.

描述（由申请人提供）：该职业发展奖（K01）将为候选人提供必要的技能，以发展一个独立的研究项目，重点是使用基于人口的数据来确定儿童逆境与后期情绪和焦虑障碍之间联系的心理，生理和环境机制，并检查遗传因素在改变逆境儿童发展轨迹中的作用。尽管不良的童年经历，如虐待和遭受家庭暴力，占人口中精神障碍的很大比例，但这些关联背后的复杂发展途径仍然缺乏特征。当前应用程序的总体目标是测试一个发展流行病学模型，该模型假设情绪和生理反应作为一种机制的中心作用，将童年逆境与随后的情绪和焦虑障碍的发作联系起来。该模型预测，在具有特定基因多态性的个体中，童年的逆境更有可能引发更高的情绪反应，这些基因多态性会增加对压力的脆弱性。该培训计划旨在为候选人提供发展精神病理学，压力生物学和心理生理学以及遗传流行病学方面的技能。具体而言，候选人将获得以下方面的知识和技能：a)开展发展方面的研究，以确定将童年逆境与情绪和焦虑障碍联系起来的心理和生理机制；B)设计、实施和分析基因信息性研究；C)确定生物学上合理的表型，将基因型、童年逆境、情绪和焦虑障碍联系起来；d)对遭受童年逆境的个体进行前瞻性流行病学研究，评估遗传和环境风险因素。这些技能将通过教学培训、指导阅读和指导研究项目的结合来发展。拟议的研究计划包括原始数据收集和现有流行病学数据分析的结合。候选人将从青少年社区样本中收集精神病理学、心理生理学、经验抽样和遗传数据，以检验概念模型的中心假设。心理生理学方法和候选基因方法将被用来定义一种潜在的表型，包括与遗传脆弱性、童年逆境暴露、情绪和焦虑障碍相关的情绪和生理反应增强。概念模型还将通过三个纵向流行病学数据集的分析进行测试：国家共病调查II，儿童和父母的雅芳纵向研究和护士健康研究II，其中两个测量遗传和环境风险因素。培训活动和结果将用于开发一项前瞻性流行病学研究的R01申请，该研究评估遗传和环境风险因素，旨在确定将童年逆境与情绪和焦虑障碍的发病联系起来的发育途径。

DESCRIPTION (provided by applicant): This Career Development Award (K01) will provide the candidate with the necessary skills to develop an independent research program focused on using population-based data to identify the psychological, physiological, and environmental mechanisms underlying the association between childhood adversity and the later onset of mood and anxiety disorders and to examine the role of genetic factors in altering developmental trajectories among children exposed to adversity. Although adverse childhood experiences, such as maltreatment and exposure to family violence, account for a substantial proportion of mental disorders in the population, the complex developmental pathways that underlie these associations remain poorly characterized. The overall aim of the current application is to test a developmental epidemiologic model that posits a central role of emotional and physiological reactivity as a mechanism linking childhood adversity to the subsequent onset of mood and anxiety disorders. The model predicts that childhood adversity is more likely to trigger heightened emotional reactivity among individuals with specific genetic polymorphisms that increase vulnerability to stress. The training plan is designed to provide the candidate with skills in developmental psychopathology, stress biology and psychophysiology, and genetic epidemiology. Specifically, the candidate will acquire the knowledge and skills to: a) conduct developmentally informed studies to identify psychological and physiological mechanisms linking childhood adversity to mood and anxiety disorders; b) design, conduct, and analyze genetically informative studies; c) identify biologically plausible phenotypes that link genotype, childhood adversity, and mood and anxiety disorders; and d) conduct prospective epidemiologic studies of individuals exposed to childhood adversities, which assess both genetic and environmental risk factors. These skills will be developed through a combination of didactic training, guided readings, and mentored research projects. The proposed research program involves a combination of original data collection and analysis of existing epidemiologic data. The candidate will collect psychopathology, psychophysiology, experience sampling, and genetic data from a community sample of adolescents to examine the central hypotheses of the conceptual model. Psychophysiology methods and a candidate gene approach will be used to define a potential phenotype involving heightened emotional and physiological reactivity that links genetic vulnerability, childhood adversity exposure, and mood and anxiety disorders. The conceptual model also will be tested through analysis of three longitudinal epidemiologic data sets: the National Comorbidity Survey II, the Avon Longitudinal Study of Children and Parents, and the Nurses' Health Study II, two of which measure both genetic and environmental risk factors. Training activities and results will be used to develop an R01 application for a prospective epidemiologic study that assesses both genetic and environmental risk factors and aims to identify developmental pathways linking childhood adversity to the onset of mood and anxiety disorders. PUBLIC HEALTH RELEVANCE: The proposed research aims to identify psychological and physiological mechanisms underlying the association between childhood adversity and the later onset of mood and anxiety disorders and to determine whether genetic polymorphisms associated with the stress response system modify developmental trajectories among individuals exposed to childhood adversity, including maltreatment and family violence. Elucidation of these mechanisms, and the role of genetic vulnerability in altering mediating pathways, is critical to inform the development of preventive interventions targeting children exposed to adversity. Given that a substantial proportion of mental disorders in the population are directly attributable to childhood adversity, the development of such interventions represents an important public health priority.