Polygenic risk for depression, anxiety and neuroticism are associated with the severity and rate of change in depressive symptoms across adolescence
Polygenic risk for depression, anxiety and neuroticism are associated with the severity and rate of change in depressive symptoms across adolescence
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DOI：
10.1111/jcpp.13422
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发表时间：
2021-03-28
影响因子：
7.6
通讯作者：
Tilling, Kate
中科院分区：
文献类型：
--
作者：
Kwong, Alex S. F.;Morris, Tim T.;Tilling, Kate
背景：青春期是抑郁症最容易发作的时期。双胞胎研究表明，基因影响在青春期抑郁症的发展和变化中起着重要作用。最近的全基因组关联研究强调，常见的遗传变异——可以合并成多基因风险评分（PRS）——也与抑郁症有关。然而，PRS在青少年抑郁中的作用和青少年抑郁的变化尚不清楚。我们的目的是通过使用横断面和生长曲线模型来检验在青春期测量的五种精神特征和抑郁症状的PRS之间的关联。5种PRS分别为：抑郁（DEP）、重度抑郁障碍（MDD）、焦虑（ANX）、神经质（NEU）和精神分裂症（SCZ）。方法：我们使用来自雅芳父母与儿童纵向研究（ALSPAC）的6000多名参与者的数据，从10到24年的时间跨度中，共9次检查了5种PRS与自我报告的抑郁症状（短期情绪和感觉问卷）之间的关联。PRS是根据在成年人群中进行的全基因组关联研究创建的。我们检查了每个年龄段的PRS之间的横断面关联，然后在重复测量框架中再次使用多层生长曲线分析来检查抑郁症状的严重程度和变化率。结果：有强有力的证据表明，在我们的横断面分析中，DEP、MDD和NEU的高PRS与整个青春期和青年期更严重的抑郁症状相关，在所有9种情况下观察到一致的关联。生长曲线分析提供了更强的关联（通过效应大小测量）和额外的见解，表明DEP、MDD和NEU PRS较高的个体在整个发展过程中抑郁症状的轨迹更陡峭，所有这些都在青春期有更大的变化率。在横断面分析中，ANX和SCZ PRS的证据不太一致，但在使用ANX PRS的生长曲线分析中，有一些证据表明青春期的变化率增加。这些结果表明，由不同精神病学PRS索引的常见遗传变异显示出特异性模式，影响整个青春期和青年期抑郁症状的严重程度和变化率。利用重复测量设计的纵向数据有可能提供更深入的见解，遗传因素如何影响青少年抑郁症的发病和持续。
Background Adolescence marks a period where depression will commonly onset. Twin studies show that genetic influences play a role in how depression develops and changes across adolescence. Recent genome-wide association studies highlight that common genetic variants - which can be combined into polygenic risk scores (PRS) - are also implicated in depression. However, the role of PRS in adolescent depression and changes in adolescent depression is not yet understood. We aimed to examine associations between PRS for five psychiatric traits and depressive symptoms measured across adolescence using cross-sectional and growth-curve models. The five PRS were as follows: depression (DEP), major depressive disorder (MDD), anxiety (ANX), neuroticism (NEU) and schizophrenia (SCZ).Methods We used data from over 6,000 participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine associations between the five PRS and self-reported depressive symptoms (Short Mood and Feelings Questionnaire) over 9 occasions from 10 to 24 years. The PRS were created from well-powered genome-wide association studies conducted in adult populations. We examined cross-sectional associations between the PRS at each age and then again with longitudinal trajectories of depressive symptoms in a repeated measures framework using multilevel growth-curve analysis to examine the severity and the rate of change.Results There was strong evidence that higher PRS for DEP, MDD and NEU were associated with worse depressive symptoms throughout adolescence and into young adulthood in our cross-sectional analysis, with consistent associations observed across all nine occasions. Growth-curve analyses provided stronger associations (as measured by effect sizes) and additional insights, demonstrating that individuals with higher PRS for DEP, MDD and NEU had steeper trajectories of depressive symptoms across development, all with a greater increasing rate of change during adolescence. Evidence was less consistent for the ANX and SCZ PRS in the cross-sectional analysis, yet there was some evidence for an increasing rate of change in adolescence in the growth-curve analyses with the ANX PRS.Conclusions These results show that common genetic variants as indexed by varying psychiatric PRS show patterns of specificity that influence both the severity and rate of change in depressive symptoms throughout adolescence and then into young adulthood. Longitudinal data that make use of repeated measures designs have the potential to provide greater insights how genetic factors influence the onset and persistence of adolescent depression.