Abstract: Despite the fast accumulating evidence for genetic underpinnings of depression, most of these studies taken a static perspective, whereas few studies have examined the dynamic change of genetic effects over development. Moreover, emerging evidences suggest that the genetic effects of depression vary with age. The present study aimed to review the evidence of changing genetic effects on depression over development, and further explored the potential factors which play significant role in dynamically changing system. Both quantitative genetics and molecular genetics studies suggest that the genetic effects of depression vary with age. On the one hand, the heritability of depression changes over development. More specifically, the majority of studies indicated that the heritability of depression increased from childhood to adolescence. To our knowledge, there are only two studies have examined the changes of heritability from youths to adults; however, mixed findings were obtained. It is possible that these studies ignored distinguishing adolescence into different stage. The heritability of depression increased from early adolescence to middle adolescence but decreased thereafter. Similarity, molecular genetics research indicated that the main effects of genes and the gene by environment interactions exhibited age-related changes. The bulk of prior research suggests that early adolescence is a critical stage of development for observing potential changes in genetic effect. However, the change of heritability or genotype is not enough to generalize dynamic genetic effects. Whether genetic factor contribute to change or to stability in depression across time is the other critical question. Multivariate genetic model indicated that stable genetic influences operational at the first time point accounted partly for continuity of depression. More importantly, new emerging genetic effects appear at early or middle adolescence that coincides with increases in depressive symptoms. New genetic influences may explain age-related increases in depression across development. Furthermore, molecular genetics research found that genetic factors influenced the developmental trajectories, including normative and heterogeneous developmental trajectories. We reviewed the potential mechanism that account for dynamic genetic effect. It is possible that hormone and neurobiological protein changes in different critical maturational periods may alter gene expression or function related to depression, and thereby contributed to the change of genetic effect. Research has demonstrated that changes in environment may alter epigenetic modifications, and as a result, different phenotypes can be generated from a single genotype through the lifespan. Moreover, cascade models may explain the pathways by which genetic effects changes over time to shape development through processes of multilevel dynamics. Previous studies have highlighted the value in taking a dynamic perspective in investigating genetic effects on depression; future research should employ longitudinal design spanning a wide age range to reveal the developmental changes of the effect of genetic variants and their interactions with environment on depression. Exploring underlying mechanism and gender differences in genetic changes by including brain function, hormone, neurobiological protein and epigenetic indexes remain an important direction for future research.

Key words: depression, genetic effect, dynamic, epigenetic, cascade model

摘要： 抑郁的遗传效应存在发展动态性。一方面，在发展过程中，抑郁的遗传率会发生改变，抑郁的风险基因及其与环境的交互作用模式也存在动态变化。另一方面，遗传因素会影响抑郁的发展变化模式。通过梳理既有相关研究，本文从生理成熟因素、表观遗传和发展级联效应三方面分析抑郁遗传效应发展动态性的原因。未来研究应区分重要发展阶段，增加脑功能、性激素、神经生物蛋白以及表观遗传等指标考察抑郁遗传效应的变化模式及其发生机制。

关键词: 抑郁, 遗传效应, 动态性, 表观遗传, 发展级联