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基于社区样本的注意缺陷多动障碍多基因风险评分与大脑功能网络分离。

Polygenic risk score for attention-deficit/hyperactivity disorder and brain functional networks segregation in a community-based sample.

机构信息

Center of Mathematics, Computing, and Cognition, Universidade Federal do ABC, Santo André, Brazil.

Laboratory of Integrative Neuroscience (LiNC), Universidade Federal de São Paulo (UNIFESP), Sao Paulo, Brazil.

出版信息

Genes Brain Behav. 2023 Apr;22(2):e12838. doi: 10.1111/gbb.12838. Epub 2023 Feb 21.

Abstract

Neuroimaging studies suggest that brain development mechanisms might explain at least some behavioural and cognitive attention-deficit/hyperactivity disorder (ADHD) symptoms. However, the putative mechanisms by which genetic susceptibility factors influence clinical features via alterations of brain development remain largely unknown. Here, we set out to integrate genomics and connectomics tools by investigating the associations between an ADHD polygenic risk score (ADHD-PRS) and functional segregation of large-scale brain networks. With this aim, ADHD symptoms score, genetic and rs-fMRI (resting-state functional magnetic resonance image) data obtained in a longitudinal community-based cohort of 227 children and adolescents were analysed. A follow-up was conducted approximately 3 years after the baseline, with rs-fMRI scanning and ADHD likelihood assessment in both stages. We hypothesised a negative correlation between probable ADHD and the segregation of networks involved in executive functions, and a positive correlation with the default-mode network (DMN). Our findings suggest that ADHD-PRS is correlated with ADHD at baseline, but not at follow-up. Despite not surviving for multiple comparison correction, we found significant correlations between ADHD-PRS and segregation of cingulo-opercular networks and DMN at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation. These directions of associations corroborate the proposed counter-balanced role of attentional networks and DMN in attentional processes. However, the association between ADHD-PRS and brain networks functional segregation was not found at follow-up. Our results provide evidence for specific influences of genetic factors on development of attentional networks and DMN. We found significant correlations between polygenic risk score for ADHD (ADHD-PRS) and segregation of cingulo-opercular networks and default-mode network (DMN) at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation.

摘要

神经影像学研究表明,大脑发育机制至少可以解释一些行为和认知注意力缺陷/多动障碍(ADHD)症状。然而,遗传易感性因素通过改变大脑发育来影响临床特征的潜在机制在很大程度上仍然未知。在这里,我们通过研究 ADHD 多基因风险评分(ADHD-PRS)与大脑大尺度网络功能分离之间的关联,整合了基因组学和连接组学工具。为此,我们分析了 227 名儿童和青少年的 ADHD 症状评分、遗传和 rs-fMRI(静息态功能磁共振成像)数据,这些数据是在一个基于社区的纵向队列中获得的。大约在基线后 3 年进行了随访,在两个阶段都进行了 rs-fMRI 扫描和 ADHD 可能性评估。我们假设 ADHD 与执行功能相关的网络的分离呈负相关,与默认模式网络(DMN)呈正相关。我们的研究结果表明,ADHD-PRS 与基线时的 ADHD 相关,但与随访时不相关。尽管未通过多重比较校正,但我们发现 ADHD-PRS 与基线时的扣带-顶叶网络和 DMN 分离之间存在显著相关性。ADHD-PRS 与扣带-顶叶网络的分离水平呈负相关,与 DMN 的分离呈正相关。这些关联方向证实了注意力网络和 DMN 在注意力过程中的平衡作用。然而,在随访时未发现 ADHD-PRS 与大脑网络功能分离之间的关联。我们的研究结果为遗传因素对注意力网络和 DMN 发育的特定影响提供了证据。我们发现 ADHD 多基因风险评分(ADHD-PRS)与扣带-顶叶网络和默认模式网络(DMN)的分离之间存在显著相关性。ADHD-PRS 与扣带-顶叶网络的分离水平呈负相关,与 DMN 的分离呈正相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc6d/10067387/eab5e3b294a7/GBB-22-e12838-g001.jpg

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