Genetic and Environmental Risk Factors Associated With Trajectories of Depression Symptoms From Adolescence to Young Adulthood
Genetic and Environmental Risk Factors Associated With Trajectories of Depression Symptoms From Adolescence to Young Adulthood
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DOI：
10.1001/jamanetworkopen.2019.6587
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发表时间：
2019-06-01
影响因子：
13.8
通讯作者：
Pearson, Rebecca M.
中科院分区：
文献类型：
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作者：
Kwong, Alex S. F.;Lopez-Lopez, Jose A.;Pearson, Rebecca M.
从青春期到成年早期抑郁情绪的不良轨迹与当前和以后的精神病理学，受教育程度受损和社会功能障碍有关，但与这些轨迹相关的遗传和环境风险因素尚未完全建立。研究什么样的危险因素与抑郁情绪的不同轨迹相关，可以帮助确定抑郁症状的性质，并改善对那些最危险的人的预防干预措施。在1990年建立的一项纵向队列研究中，目前正在进行（雅芳父母和儿童纵向研究[ALSPAC]），使用生长混合模型来确定英国9394名个体的抑郁症状轨迹。然后检查不同风险因素与这些轨迹的关联。分析于2018年8月至2019年1月进行。主要结局和指标轨迹由10至24岁9次使用简短情绪和感觉问卷测量的抑郁症状组成。风险因素包括性别，一个多基因的风险评分从最近的全基因组关联研究抑郁症症状，母亲产后抑郁症，合作伙伴虐待子女的母亲时，孩子是2至4岁，儿童焦虑在8岁，并被欺负在10岁的年龄。其中女性1771人（50.2%）。在平均（SD）年龄10.7（0.3）岁和平均（SD）年龄23.8（0.5）岁之间评估轨迹。总体而言，确定了抑郁症状的5种不同轨迹：（1）稳定低位（2506人[71.1%]），（2）青少年有限（325例[9.2%]），（3）儿童期受限（203例[5.8%]），（4）早期成人发作（393例[11.1%]），（5）儿童期持续性（98例[2.8%]）。在所有与轨迹相关的风险因素中，性别（比值比[OR]，6.45; 95%CI，2.89-14.38），抑郁症状的多基因风险评分（OR，1.47; 95%CI，1.10-1.96），儿童期焦虑（OR，1.30; 95%CI，1.16-1.45）显示与儿童期抑郁症状的持续轨迹相比，稳定低轨迹的关联最强。母亲产后抑郁症（OR，2.39; 95%CI，1.41-4.07）与早发成年人发病轨迹的相关性最强，而伴侣虐待母亲（OR，2.30; 95%CI，1.36-3.90）与早发成年人发病轨迹的相关性最强。欺凌（OR，8.08; 95%CI，4.92-13.26）显示与儿童期限制的轨迹最强的关联。（儿童期持续性和早期成人发病）与遗传和环境风险因素有关，但在成年早期解决的2个有限持续时间的轨迹（儿童期有限和青少年期有限）与多基因风险评分或母亲产后抑郁症无关。欺凌与儿童期持续和儿童期有限的轨迹密切相关，这表明这种风险因素可能具有特定的时间效应。这些研究结果表明，检查遗传和多个特定时间的环境前因可以帮助确定不同的发病和慢性的轨迹。
IMPORTANCE Less favorable trajectories of depressive mood from adolescence to early adulthood are associated with current and later psychopathology, impaired educational attainment, and social dysfunction, yet the genetic and environmental risk factors associated with these trajectories are not fully established. Examining what risk factors are associated with different trajectories of depressive mood could help identify the nature of depression symptoms and improve preventive interventions for those at most risk.OBJECTIVE To examine the differential associations of genetic and environmental risk factors with trajectories of depression symptoms among individuals observed from ages 10 to 24 years.DESIGN, SETTING, AND PARTICIPANTS In a longitudinal cohort study established in 1990 and currently ongoing (the Avon Longitudinal Study of Parents and Children [ALSPAC]), growth mixture modeling was used to identify trajectories of depression symptoms in 9394 individuals in the United Kingdom. Associations of different risk factors with these trajectories were then examined. Analysis was conducted between August 2018 and January 2019.MAIN OUTCOMES AND MEASURES Trajectories were composed from depression symptoms measured using the Short Mood and Feelings Questionnaire at 9 occasions from ages 10 to 24 years. Risk factors included sex, a polygenic risk score taken from a recent genome-wide association study of depression symptoms, maternal postnatal depression, partner cruelty to the offspring's mother when the child was aged 2 to 4 years, childhood anxiety at age 8 years, and being bullied at age 10 years.RESULTS Data on all risk factors, confounders, and the outcome were available for 3525 individuals, including 1771 (50.2%) who were female. Trajectories were assessed between the mean (SD) age of 10.7 (0.3) years and mean (SD) age of 23.8 (0.5) years. Overall, 5 distinct trajectories of depression symptoms were identified: (1) stable low (2506 individuals [71.1%]), (2) adolescent limited (325 individuals [9.2%]), (3) childhood limited (203 individuals [5.8%]), (4) early-adult onset (393 individuals [11.1%]), and (5) childhood persistent (98 individuals [2.8%]). Of all the associations of risk factors with trajectories, sex (odds ratio [OR], 6.45; 95% CI, 2.89-14.38), the polygenic risk score for depression symptoms (OR, 1.47; 95% CI, 1.10-1.96), and childhood anxiety (OR, 1.30; 95% CI, 1.16-1.45) showed the strongest association with the childhood-persistent trajectory of depression symptoms compared with the stable-low trajectory. Maternal postnatal depression (OR, 2.39; 95% CI, 1.41-4.07) had the strongest association with the early-adult-onset trajectory, while partner cruelty to mother (OR, 2.30; 95% CI, 1.36-3.90) had the strongest association with the adolescent-limited trajectory. Bullying (OR, 8.08; 95% CI, 4.92-13.26) showed the strongest association with the childhood-limited trajectory.CONCLUSIONS AND RELEVANCE The least favorable trajectories of depression symptoms (childhood persistent and early-adult onset) were associated with both genetic and environmental risk factors, but the 2 trajectories of limited duration that had resolved by early adulthood (childhood limited and adolescent limited) were not associated with the polygenic risk score or maternal postnatal depression. Bullying was strongly associated with both the childhood-persistent and childhood-limited trajectories, suggesting that this risk factor may have a time-specific effect. These findings suggest that examining genetic and multiple time-specific environmental antecedents could help identify trajectories of varying onset and chronicity.