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

描述(申请人提供)：这一职业发展奖(K01)将为候选人提供必要的技能，以开发一个独立的研究计划，重点是使用基于人口的数据，以确定潜在的心理，生理和环境机制之间的联系，童年逆境和情绪和焦虑症的后期发作，并检查遗传因素在改变儿童在逆境中的发展轨迹的作用。尽管虐待和遭受家庭暴力等不良童年经历在人口中的精神障碍中占很大比例，但作为这些联系基础的复杂发展道路仍然缺乏特点。目前应用的总体目标是测试一种发育流行病学模型，该模型假定情绪和生理反应是将童年逆境与随后的情绪和焦虑症发病联系起来的一种机制。该模型预测，童年的逆境更有可能引发具有特定基因多态的个体的情绪反应增强，这些基因多态增加了对压力的脆弱性。培训计划旨在为应聘者提供发展精神病理学、应激生物学和心理生理学以及遗传流行病学方面的技能。具体地说，候选人将获得以下知识和技能：a)进行发育知情研究，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、进行和分析遗传信息研究；c)确定将基因、童年逆境以及情绪和焦虑症联系起来的生物学上可信的表型；以及d)对暴露于童年逆境中的个人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、指导性阅读和有指导的研究项目相结合来发展。拟议的研究计划涉及原始数据收集和对现有流行病学数据的分析相结合。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。将使用心理生理学方法和候选基因方法来定义潜在的表型，包括高情感和生理反应，将遗传脆弱性、童年逆境暴露以及情绪和焦虑障碍联系起来。概念模型还将通过对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、雅芳儿童和父母纵向研究以及护士健康研究II，其中两个数据集既衡量遗传风险因素，也衡量环境风险因素。培训活动和结果将用于开发R01应用程序，用于前瞻性流行病学研究，评估遗传和环境风险因素，并旨在确定将童年逆境与情绪和焦虑症的发病联系起来的发展途径。

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.