Abstract：
Based on a multiwave, two-year prospective design, this study is the first to examine the extent to which multilocus hypothalamic-pituitary-adrenal axis (HPA axis)-related genetic variants, childhood maltreatment, and recent stress jointly predicted prospective changes in adolescent depressive symptoms. A theory-driven multilocus genetic profile score (MGPS) was calculated to combine the effects of six common polymorphisms within HPA-axis related genes (CRHR1, NR3C1, NR3C2, FKBP5, COMT, and HTR1A) in a sample of Chinese Han adolescents (N = 827; 50.2% boys; Mage = 16.45 ± 1.36 years). The results showed that the three-way interaction of HPA-axis related MGPS, childhood maltreatment and recent interpersonal, but not noninterpersonal, stress significantly predicted prospective changes in adolescent depressive symptoms. For adolescents with high but not low HPA-axis related MGPS, exposure to severe childhood maltreatment predisposed individuals more vulnerable to recent interpersonal stress, exhibiting greater prospective changes in adolescent depressive symptoms. The findings provide preliminary evidence for the cumulative risk mechanism regarding gene-by-environment-by-environment (G × E1 × E2) interactions that underlie the longitudinal development of adolescent depressive symptoms and show effects specific to interpersonal stress.
摘要：
基于多波，两年的前瞻性设计，这项研究是第一个检查多基因座下丘脑-垂体-肾上腺轴（HPA轴）相关遗传变异的程度，童年虐待,和最近的压力共同预测了青少年抑郁症状的前瞻性变化。计算了理论驱动的多位点遗传谱评分（MGPS），以结合HPA轴相关基因（CRHR1，NR3C1，NR3C2，FKBP5，COMT，和HTR1A）在中国汉族青少年样本中（N=827；50.2％的男孩；Mage=16.45±1.36岁）。结果表明，HPA轴相关MGPS的三向相互作用，童年虐待和最近的人际关系，但不是非人际关系，压力显着预测了青少年抑郁症状的前瞻性变化。对于高但不低HPA轴相关MGPS的青少年，暴露于严重的儿童虐待易感个体更容易受到最近的人际压力，在青少年抑郁症状方面表现出更大的前瞻性变化。研究结果为青少年抑郁症状纵向发展的基因-环境-环境（G×E1×E2）相互作用的累积风险机制提供了初步证据，并显示了对人际压力的特定影响。
