Gene-environment Interaction in Adolescent Depression

描述(申请人提供)：多条证据表明单胺类神经传递、环境应激及其相互作用在抑郁症病因中起着重要作用。该项目将通过模拟环境风险和影响神经传递的候选基因的直接和交互影响，在青少年和年轻人中研究这一过程。利用国家青少年健康纵向研究，混合回归模型将通过对几个候选基因的全面检查和对环境风险的更微妙的概念化来扩展现有的横断面模型。此外，使用潜伏曲线模型，对候选基因之间的主效应、上位性和基因-环境相互作用(GxE)以及环境风险进行纵向分析，将对青春期和青春期抑郁症的轨迹进行建模。将区分近端和远端环境风险，并评估近端环境因素对远端因素的主要和GxE影响的调节程度。最后，由于遗传结构和社会影响可能因群体不同而不同，将通过按种族/民族和性别对所有分析进行分层来检查效果异质性。

DESCRIPTION (provided by applicant): Several lines of evidence indicate monoaminergic neurotransmission, environmental stress and their interaction play prominent roles in depression etiology. This project will investigate this process in adolescents and young adults by modeling the direct and interactive effects of environmental risk and candidate genes influencing neurotransmission. Using the National Longitudinal Study of Adolescent Health, mixed regression models will extend existing cross-sectional models through comprehensive examination of several candidate genes and more nuanced conceptualization of environmental risk. Further, using latent curve models, longitudinal analyses of main effects, epistasis and gene-environment interaction (GxE) among candidate genes and environmental risk will model trajectories of depression across adolescence and into young adulthood. Proximate and distal environmental risk will be distinguished and the degree to which proximate environmental factors moderate the main and GxE effects of distal factors will be assessed. Finally, as genetic architecture and social influences may vary by group, effect heterogeneity will be examined by stratifying all analyses by race/ethnicity and gender.