Department of Public Health Sciences, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA.
Department of Public Health Sciences, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA.
J Psychiatr Res. 2022 Aug;152:187-193. doi: 10.1016/j.jpsychires.2022.06.019. Epub 2022 Jun 14.
A polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) has been found to be associated with ADHD in multiple studies, but also with many other dimensions of problems. Little is known, however, about the processes underlying these transdiagnostic associations. Using data from the baseline and 1-year follow-up assessments of 9- to 10-year-old children in the Adolescent Brain Cognitive Development™ (ABCD©) Study, associations were assessed between an ADHD PRS and both general and specific factors of psychological problems defined in bifactor modeling. Additionally, prospective mediated paths were tested from the ADHD PRS to dimensions of problems in the follow-up assessment through baseline measures of executive functioning (EF) and two facets of impulsivity: lower perseverance and greater impulsiveness in the presence of surgent positive emotions. Previous findings of modest but significant direct associations of the ADHD PRS with the general factor of psychological problems were replicated in both assessments in 4,483 children of European ancestry. In addition, significant statistical mediation was found from the ADHD PRS to the general factor, specific ADHD, and conduct problems in the follow-up assessment through each of the two facets of impulsivity. In contrast, EF did not statistically mediate associations between the ADHD PRS and psychological problems. These results suggest that polygenic risk transdiagnostically influences both psychological problems and facets of impulsivity, perhaps partly through indirect pathways via facets of impulsivity.
多基因风险评分(PRS)已被发现与注意力缺陷多动障碍(ADHD)在多项研究中相关,但也与许多其他问题维度相关。然而,对于这些跨诊断关联的潜在机制知之甚少。本研究使用了青少年大脑认知发展研究(ABCD©研究)中 9-10 岁儿童基线和 1 年随访评估的数据,评估了 ADHD PRS 与双因素模型中定义的心理问题的一般和特定因素之间的关联。此外,通过基线执行功能(EF)和两种冲动性方面的测量,从 ADHD PRS 到随访评估中问题维度测试了前瞻性中介路径:在 Surgent 积极情绪存在下较低的毅力和更大的冲动性。在欧洲血统的 4483 名儿童的两项评估中,重复了 ADHD PRS 与心理问题一般因素之间适度但显著的直接关联的先前发现。此外,通过两种冲动性方面的每一种,在随访评估中从 ADHD PRS 到一般因素、特定 ADHD 和品行问题都发现了显著的统计中介作用。相比之下,EF 并没有在 ADHD PRS 和心理问题之间的关联中起到统计学上的中介作用。这些结果表明,多基因风险跨诊断地影响心理问题和冲动性方面,可能部分通过冲动性方面的间接途径。