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

IF 2.4 4区心理学 Q2 BEHAVIORAL SCIENCES

Genes Brain and Behavior Pub Date : 2023-02-21 DOI:10.1111/gbb.12838

João Ricardo Sato, Claudinei Eduardo Biazoli, Ana Paula Arantes Bueno, Arthur Caye, Pedro Mario Pan, Marcos Santoro, Jessica Honorato-Mauer, Giovanni Abrahão Salum, Marcelo Queiroz Hoexter, Rodrigo Affonseca Bressan, Andrea Parolin Jackowski, Euripedes Constantino Miguel, Sintia Belangero, Luis Augusto Rohde

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引用次数: 0

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.

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以社区为基础的样本中注意缺陷/多动障碍和脑功能网络分离的多基因风险评分

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影响临床特征的推测机制仍然很大程度上未知。在这里，我们通过研究ADHD多基因风险评分(ADHD- prs)与大规模脑网络功能分离之间的关系，着手整合基因组学和连接组学工具。为此，对227名儿童和青少年的纵向社区队列中获得的ADHD症状评分、遗传和rs-fMRI(静息状态功能磁共振图像)数据进行了分析。在基线后约3年进行随访，在两个阶段进行rs-fMRI扫描和ADHD可能性评估。我们假设可能的ADHD与涉及执行功能的网络分离之间存在负相关，而与默认模式网络(DMN)呈正相关。我们的研究结果表明，ADHD- prs与ADHD在基线时相关，但在随访时无关。尽管没有经过多次比较校正，但我们发现ADHD-PRS与眼窝-眼窝网络和DMN的分离在基线时存在显著相关性。ADHD-PRS与眼窝网络分离水平呈负相关，与DMN分离水平呈正相关。这些关联方向证实了注意网络和DMN在注意过程中的平衡作用。然而，在随访中没有发现ADHD-PRS与脑网络功能分离之间的联系。本研究结果为遗传因素对注意网络和DMN发育的具体影响提供了证据。我们发现ADHD的多基因风险评分(ADHD- prs)与基线时扣眼-眼窝网络和默认模式网络(DMN)的分离存在显著相关性。ADHD-PRS与眼窝网络分离水平呈负相关，与DMN分离水平呈正相关。

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来源期刊

Genes Brain and Behavior 医学-行为科学

CiteScore

6.80

自引率

4.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Genes, Brain and Behavior was launched in 2002 with the aim of publishing top quality research in behavioral and neural genetics in their broadest sense. The emphasis is on the analysis of the behavioral and neural phenotypes under consideration, the unifying theme being the genetic approach as a tool to increase our understanding of these phenotypes. Genes Brain and Behavior is pleased to offer the following features: 8 issues per year online submissions with first editorial decisions within 3-4 weeks and fast publication at Wiley-Blackwells High visibility through its coverage by PubMed/Medline, Current Contents and other major abstracting and indexing services Inclusion in the Wiley-Blackwell consortial license, extending readership to thousands of international libraries and institutions A large and varied editorial board comprising of international specialists.