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儿童和青少年注意缺陷多动障碍症状不同发展轨迹的神经和遗传基础。

The neural and genetic underpinnings of different developmental trajectories of Attention-Deficit/Hyperactivity Symptoms in children and adolescents.

机构信息

State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, 100875, China.

IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China.

出版信息

BMC Med. 2024 Jun 3;22(1):223. doi: 10.1186/s12916-024-03449-1.


DOI:10.1186/s12916-024-03449-1
PMID:38831366
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11149188/
Abstract

BACKGROUND: The trajectory of attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents, encompassing descending, stable, and ascending patterns, delineates their ADHD status as remission, persistence or late onset. However, the neural and genetic underpinnings governing the trajectory of ADHD remain inadequately elucidated. METHODS: In this study, we employed neuroimaging techniques, behavioral assessments, and genetic analyses on a cohort of 487 children aged 6-15 from the Children School Functions and Brain Development project at baseline and two follow-up tests for 1 year each (interval 1: 1.14 ± 0.32 years; interval 2: 1.14 ± 0.30 years). We applied a Latent class mixed model (LCMM) to identify the developmental trajectory of ADHD symptoms in children and adolescents, while investigating the neural correlates through gray matter volume (GMV) analysis and exploring the genetic underpinnings using polygenic risk scores (PRS). RESULTS: This study identified three distinct trajectories (ascending-high, stable-low, and descending-medium) of ADHD symptoms from childhood through adolescence. Utilizing the linear mixed-effects (LME) model, we discovered that attention hub regions served as the neural basis for these three developmental trajectories. These regions encompassed the left anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), responsible for inhibitory control; the right inferior parietal lobule (IPL), which facilitated conscious focus on exogenous stimuli; and the bilateral middle frontal gyrus/precentral gyrus (MFG/PCG), accountable for regulating both dorsal and ventral attention networks while playing a crucial role in flexible modulation of endogenous and extrinsic attention. Furthermore, our findings revealed that individuals in the ascending-high group exhibited the highest PRS for ADHD, followed by those in the descending-medium group, with individuals in the stable-low group displaying the lowest PRS. Notably, both ascending-high and descending-medium groups had significantly higher PRS compared to the stable-low group. CONCLUSIONS: The developmental trajectory of ADHD symptoms in the general population throughout childhood and adolescence can be reliably classified into ascending-high, stable-low, and descending-medium groups. The bilateral MFG/PCG, left ACC/mPFC, and right IPL may serve as crucial brain regions involved in attention processing, potentially determining these trajectories. Furthermore, the ascending-high pattern of ADHD symptoms exhibited the highest PRS for ADHD.

摘要

背景:注意力缺陷多动障碍(ADHD)症状在儿童和青少年中的轨迹,包括下降、稳定和上升模式,将其 ADHD 状态划分为缓解、持续或晚发。然而,控制 ADHD 轨迹的神经和遗传基础仍未得到充分阐明。

方法:在这项研究中,我们使用神经影像学技术、行为评估和遗传分析,对来自儿童学校功能和大脑发育项目的 487 名 6-15 岁的儿童进行了研究。这些儿童在基线时和之后两次随访测试中各进行了 1 年的测试(间隔 1:1.14±0.32 年;间隔 2:1.14±0.30 年)。我们应用潜在类别混合模型(LCMM)来识别儿童和青少年 ADHD 症状的发展轨迹,同时通过灰质体积(GMV)分析来研究神经相关性,并使用多基因风险评分(PRS)来探索遗传基础。

结果:本研究从儿童期到青春期,确定了 ADHD 症状的三种不同轨迹(上升高、稳定低和下降中)。利用线性混合效应(LME)模型,我们发现注意枢纽区域是这三种发展轨迹的神经基础。这些区域包括负责抑制控制的左前扣带皮层/内侧前额叶皮层(ACC/mPFC);促进对外源性刺激有意识关注的右顶下小叶(IPL);以及负责调节背侧和腹侧注意网络的双侧额中回/中央前回(MFG/PCG),同时在灵活调节内源性和外源性注意方面起着关键作用。此外,我们的研究结果表明,上升高组的个体 ADHD PRS 最高,其次是下降中组,稳定低组的个体 ADHD PRS 最低。值得注意的是,上升高组和下降中组的 PRS 均显著高于稳定低组。

结论:在一般人群中,ADHD 症状的发展轨迹在儿童期到青春期可以可靠地分为上升高、稳定低和下降中三组。双侧 MFG/PCG、左 ACC/mPFC 和右 IPL 可能是参与注意处理的关键脑区,可能决定了这些轨迹。此外,ADHD 症状的上升高模式表现出最高的 ADHD PRS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36bc/11149188/e717e2b565ae/12916_2024_3449_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36bc/11149188/a90d5bb0ce89/12916_2024_3449_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36bc/11149188/00d5826b484f/12916_2024_3449_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36bc/11149188/aaac9ce81e2b/12916_2024_3449_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36bc/11149188/e717e2b565ae/12916_2024_3449_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36bc/11149188/a90d5bb0ce89/12916_2024_3449_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36bc/11149188/00d5826b484f/12916_2024_3449_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36bc/11149188/aaac9ce81e2b/12916_2024_3449_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36bc/11149188/e717e2b565ae/12916_2024_3449_Fig4_HTML.jpg

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本文引用的文献

[1]
Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains.

Nat Genet. 2023-2

[2]
Evidence from "big data" for the default-mode hypothesis of ADHD: a mega-analysis of multiple large samples.

Neuropsychopharmacology. 2023-1

[3]
Learning to read may help promote attention by increasing the volume of the left middle frontal gyrus and enhancing its connectivity to the ventral attention network.

Cereb Cortex. 2023-2-20

[4]
"Late-onset" ADHD symptoms in young adulthood: Is this ADHD?

J Atten Disord. 2022-8

[5]
Early and late development of hub connectivity in the human brain.

Curr Opin Psychol. 2022-4

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Attention, awareness, and the right temporoparietal junction.

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Psychol Med. 2021-3-26

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Neuroimage. 2021-5-15

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The neurodevelopmental nature of attention-deficit hyperactivity disorder in adults.

Br J Psychiatry. 2021-1

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