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探究丧亲之痛与注意缺陷多动障碍多基因风险在青少年外化行为上的基因-环境相互作用。

Investigating Gene-Environment Interplay Between Bereavement and Polygenic Risk for Attention-Deficit/Hyperactivity Disorder on Externalizing Behaviors During Adolescence.

作者信息

Espinosa Dice Ana Lucia, Garrison-Desany Henri M, Ratanatharathorn Andrew, Tiemeier Henning, Davey Smith George, Denckla Christy A

机构信息

Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Broad Institute of MIT and Harvard, Boston, Massachusetts.

出版信息

JAACAP Open. 2024 May 27;3(2):323-334. doi: 10.1016/j.jaacop.2024.04.006. eCollection 2025 Jun.

Abstract

OBJECTIVE

The death of a close friend during adolescence may have a negative impact on one's mental health. However, existing literature has focused primarily on internalizing disorders, leaving the domain of externalizing behaviors understudied. Furthermore, the role of genetics in shaping post-bereavement psychopathology is not understood. In response, we examine potential interplay between polygenic liability for attention-deficit/hyperactivity disorder (ADHD) and bereavement of a close friend in shaping risk of post-loss externalizing symptoms among adolescents.

METHOD

We examined self-reported loss of a close friend between ages 12 and 16 years and a polygenic risk score (PRS) for ADHD in a sample of 3,922 adolescents from the Avon Longitudinal Study of Parents and Children. Outcomes at age 16.5 included 2 subscales of the Strengths and Difficulties Questionnaire: hyperactivity/inattention symptoms and conduct problems. Zero-inflated negative binomial (ZINB) models addressed the zero-skewed outcome distribution, and likelihood ratio tests for model comparison were used to detect gene-environment interplay.

RESULTS

Nearly 1 in 10 adolescents reported losing a close friend. After adjusting for pre-loss psychopathology, bereavement independently predicted higher hyperactivity/inattention symptom count (bereaved vs nonbereaved: incidence rate ratio [IRR] = 1.18; 95% CI = 1.05-1.31), whereas the PRS for ADHD did not; neither were associated with the odds of zero (vs any) symptoms. Similarly, a model that included bereavement but not PRS best described the observed variation in conduct problems (bereaved vs nonbereaved: IRR = 1.40; 95% CI = 1.13-1.73).

CONCLUSION

Our findings reinforce the negative impact that losing a friend may have on an adolescent's mental health, and suggest that externalizing symptoms among bereaved youth warrant clinical attention. Results from ZINB models reveal that bereavement may aggravate the severity or number of existing externalizing symptoms among those who would exhibit externalizing problems regardless. Genetic liability for ADHD may not augment the prediction of risk for psychopathology after bereavement, although better-powered samples are needed.

摘要

目的

青少年时期亲密朋友的死亡可能会对其心理健康产生负面影响。然而,现有文献主要聚焦于内化障碍,对外化行为领域的研究较少。此外,基因在塑造丧亲后精神病理学方面的作用尚不清楚。为此,我们研究了注意力缺陷多动障碍(ADHD)的多基因易感性与亲密朋友丧亲之间在塑造青少年丧亲后外化症状风险方面的潜在相互作用。

方法

我们在来自雅芳亲子纵向研究的3922名青少年样本中,研究了自我报告的12至16岁之间亲密朋友的丧亲情况以及ADHD的多基因风险评分(PRS)。16.5岁时的结果包括优势与困难问卷的两个子量表:多动/注意力不集中症状和品行问题。零膨胀负二项式(ZINB)模型解决了零偏态结果分布问题,并使用模型比较的似然比检验来检测基因-环境相互作用。

结果

近十分之一的青少年报告失去了亲密朋友。在调整丧亲前的精神病理学后,丧亲独立预测了更高的多动/注意力不集中症状计数(丧亲者与非丧亲者:发病率比[IRR]=1.18;95%可信区间=1.05-1.31),而ADHD的PRS则没有;两者均与零(与任何)症状的几率无关。同样,一个包含丧亲但不包含PRS的模型最能描述观察到的品行问题变化(丧亲者与非丧亲者:IRR=1.40;95%可信区间=1.13-1.73)。

结论

我们的研究结果强化了失去朋友可能对青少年心理健康产生的负面影响,并表明丧亲青少年的外化症状值得临床关注。ZINB模型的结果显示,丧亲可能会加重那些无论如何都会出现外化问题的人现有的外化症状的严重程度或数量。ADHD的遗传易感性可能不会增加丧亲后精神病理学风险的预测,尽管需要样本量更大的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/179e/12166943/cd635d9555a9/gr1.jpg

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