Etiology of Adolescent Depression: Gene and Social Environment Interactions

描述(申请人提供)：抑郁症是年轻人中的一个主要公共卫生问题，目前估计影响到1%到9%的美国儿童和青少年，女性是男性的两倍。为了更深入地了解抑郁症的复杂病因，研究人员探索了基因-环境相互作用(GxE)。尽管取得了进展，但关于遗传和环境因素如何结合起来导致抑郁症的知识仍然有限。此外，该领域对“环境”的概念非常狭隘；很少有实证工作试图了解近端和远端环境的显著程度，以及这两种环境如何与遗传风险相互作用。这些知识上的差距是有问题的；如果不能更全面地了解“环境”的作用，GxE研究可能会忽视环境风险和年轻人生活中重要的病原体。在“细胞到社会”方法的指导下，这项研究将使用来自国家青少年健康纵向研究(ADD Health)的数据(波I-IV)来调查以下目的：(1)检验被发现与抑郁有关的三个基因(SLC6A4、DATI、DRD4)是否改变了最近的家庭环境(以父母虐待和虐待儿童以及亲子亲密度较低为特征)与青少年抑郁之间的关系；(2)在控制了个体风险和家庭环境后，探索远端环境(学校和社区)对青少年抑郁的独立贡献，并理清这些环境的独特作用；(3)调查SLC6A4、DAT1和DRD4是否改变了远端环境(学校/社区)与青少年抑郁之间的联系。这些目标将使用Add Health独特的遗传信息、多层次、纵向设计来实现。这些目标与NIMH的战略计划保持一致：战略1.2(“确定与精神障碍相关的遗传和环境因素”)和战略2.3(“开发工具，更好地定义/确定终生精神疾病的风险和保护因素”)和发展转化研究部(DDTR)，后者的首要任务是“在精神病理学的发展中测试包含生物、行为和经验因素的综合模型，并利用纵向研究，基于这些因素之间的组合和相互影响来跟踪风险和保护的轨迹。”这项创新的多层次研究的结果将促进跨学科知识的发展，即如何衡量环境以及何时何地干预青年的生活，以减少他们的抑郁风险并提高他们的复原力。

DESCRIPTION (provided by applicant): Depression is a major public health problem among youth, currently estimated to impact between 1% to 9% of U.S. children and adolescents and twice as many females as males. Researchers have explored gene- environment interactions (GxE) in order to more deeply understand the complex etiology of depression. Despite advances, knowledge remains limited on how genetic and environmental factors combine to contribute to depression. Moreover, the field's conceptualization of "environment" is sorely narrow; very little empirical work has tried to understand the salience of both proximal and distal environments and how both types of environments interact with genetic risks. These gaps in knowledge are problematic; without a more inclusive understanding of the role of "environment," GxE research may ignore environmental risks and pathogens important in the lives of youth. Guided by a "cells to society" approach, this study will use data (Waves I - IV) from the National Longitudinal Study of Adolescent Health (Add Health), a nationally- representative study of youth ages 12-19 at enrollment, to investigate the following aims: (1) examine whether three genes found to be linked to depression (SLC6A4, DATI, DRD4) modify the association between proximal family environments (characterized by parental abuse and maltreatment of the child and low perceived closeness between parent and child) and depression in adolescents; (2) explore, after controlling for individual risks and family environments, the independent contribution of distal environments (schools and neighborhoods) on youth depression and disentangle the unique effect of these environments; (3) investigate whether SLC6A4, DAT1, and DRD4 modify the association between distal environments (schools/neighborhoods) and depression in adolescents. These aims will be accomplished using Add Health's unique genetically-informative, multi-level, longitudinal design. These aims are aligned with NIMH's Strategic Plan: Strategy 1.2 ("Identify the genetic and environmental factors associated with mental disorders") and Strategy 2.3 ("Develop tools to better define/identify risk and protective factors for mental illness across the lifespan") and the Division of Developmental Translational Research (DDTR), whose high priority is to "test integrative models incorporating biological, behavioral, and experiential factors in the development of psychopathology, and utilize longitudinal research to track trajectories of risk and protection based on the combined and interactive influences among these factors." Results of this innovative, multi- level study will advance interdisciplinary knowledge on how to measure environment and when and where to intervene in the lives of youth to reduce their risk depression and promote their resilience.