Barcelona Institute for Global Health and the Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
Erasmus University Medical Center, Rotterdam, the Netherlands; Generation R Study Group, Erasmus University Medical Center; Amsterdam Neuroscience, VU University, Amsterdam, the Netherlands; Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, the Netherlands.
J Am Acad Child Adolesc Psychiatry. 2019 Jun;58(6):600-607. doi: 10.1016/j.jaac.2018.09.443. Epub 2019 Jan 9.
This study examined the relation between polygenic scores (PGSs) for 5 major psychiatric disorders and 2 cognitive traits with brain magnetic resonance imaging morphologic measurements in a large population-based sample of children. In addition, this study tested for differences in brain morphology-mediated associations between PGSs for psychiatric disorders and PGSs for related behavioral phenotypes.
Participants included 1,139 children from the Generation R Study assessed at 10 years of age with genotype and neuroimaging data available. PGSs were calculated for schizophrenia, bipolar disorder, major depression disorder, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, intelligence, and educational attainment using results from the most recent genome-wide association studies. Image processing was performed using FreeSurfer to extract cortical and subcortical brain volumes.
Greater genetic susceptibility for ADHD was associated with smaller caudate volume (strongest prior = 0.01: β = -0.07, p = .006). In boys, mediation analysis estimates showed that 11% of the association between the PGS for ADHD and the PGS attention problems was mediated by differences in caudate volume (n = 535), whereas mediation was not significant in girls or the entire sample. PGSs for educational attainment and intelligence showed positive associations with total brain volume (strongest prior = 0.5: β = 0.14, p = 7.12 × 10; and β = 0.12, p = 6.87 × 10, respectively).
The present findings indicate that the neurobiological manifestation of polygenic susceptibility for ADHD, educational attainment, and intelligence involve early morphologic differences in caudate and total brain volumes in childhood. Furthermore, the genetic risk for ADHD might influence attention problems through the caudate nucleus in boys.
本研究在一个大型基于人群的儿童样本中，检查了 5 种主要精神障碍和 2 种认知特征的多基因评分（PGS）与大脑磁共振成像形态测量之间的关系。此外，本研究还测试了精神障碍 PGS 与相关行为表型 PGS 之间的脑形态介导关联的差异。
参与者包括来自 Generation R 研究的 1139 名 10 岁儿童，他们的基因型和神经影像学数据可用。使用最新的全基因组关联研究的结果，为精神分裂症、双相情感障碍、重度抑郁症、注意缺陷/多动障碍（ADHD）、自闭症谱系障碍、智力和教育程度计算 PGS。使用 FreeSurfer 进行图像处理以提取皮质和皮质下脑容量。
ADHD 的遗传易感性较高与尾状核体积较小有关（最强先验值为 0.01：β=-0.07，p=0.006）。在男孩中，中介分析估计表明，ADHD PGS 与注意力问题 PGS 之间的 11%的关联是由尾状核体积差异介导的（n=535），而在女孩或整个样本中，中介作用不显著。教育程度和智力的 PGS 与总脑容量呈正相关（最强先验值为 0.5：β=0.14，p=7.12×10；β=0.12，p=6.87×10，分别）。
本研究结果表明，ADHD、教育程度和智力的多基因易感性的神经生物学表现涉及儿童期尾状核和总脑体积的早期形态差异。此外，ADHD 的遗传风险可能通过男孩的尾状核影响注意力问题。
