Etiology of Adolescent Depression: Gene and Social Environment Interactions

描述（由申请人提供）：抑郁症是青少年中的主要公共卫生问题，目前估计影响美国儿童和青少年的1%至9%，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）。尽管取得了进步，但关于遗传和环境因素如何共同导致抑郁症的知识仍然有限。此外，该领域对“环境”的概念化非常狭隘；很少有实证研究试图了解近端和远端环境的显著性，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；如果对“环境”的作用没有更全面的理解，GxE研究可能会忽视环境风险和对年轻人生活重要的病原体。在“细胞到社会”方法的指导下，本研究将使用来自全国青少年健康纵向研究（Add Health）的数据（波I - IV），这是一项全国代表性的12-19岁青少年入学研究，旨在调查以下目标：(1)研究与抑郁相关的3个基因（SLC6A4、DATI、DRD4）是否能改变近端家庭环境（以父母虐待儿童、亲子亲近感低为特征）与青少年抑郁之间的关系；(2)在控制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，并揭示这些环境的独特作用；(3)探讨SLC6A4、DAT1和DRD4是否改变远端环境（学校/邻里）与青少年抑郁的关系。这些目标将通过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，以更好地定义/识别整个生命周期中精神疾病的风险和保护因素”）以及发展转化研究部（DDTR），其高度优先事项是“测试整合精神病理学发展中的生物、行为和经验因素的综合模型”。并利用纵向研究，根据这些因素之间的综合和相互影响，追踪风险和保护的轨迹。”这项创新的、多层次的研究结果将推动跨学科的知识，研究如何测量环境，何时何地干预青少年的生活，以减少他们的抑郁风险，提高他们的适应能力。

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.