Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon 97239
Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon 97239.
J Neurosci. 2024 Mar 6;44(10):e1202232023. doi: 10.1523/JNEUROSCI.1202-23.2023.
Identification of replicable neuroimaging correlates of attention-deficit hyperactivity disorder (ADHD) has been hindered by small sample sizes, small effects, and heterogeneity of methods. Given evidence that ADHD is associated with alterations in widely distributed brain networks and the small effects of individual brain features, a whole-brain perspective focusing on cumulative effects is warranted. The use of large, multisite samples is crucial for improving reproducibility and clinical utility of brain-wide MRI association studies. To address this, a polyneuro risk score (PNRS) representing cumulative, brain-wide, ADHD-associated resting-state functional connectivity was constructed and validated using data from the Adolescent Brain Cognitive Development (ABCD, = 5,543, 51.5% female) study, and was further tested in the independent Oregon-ADHD-1000 case-control cohort ( = 553, 37.4% female). The ADHD PNRS was significantly associated with ADHD symptoms in both cohorts after accounting for relevant covariates ( < 0.001). The most predictive PNRS involved all brain networks, though the strongest effects were concentrated among the default mode and cingulo-opercular networks. In the longitudinal Oregon-ADHD-1000, non-ADHD youth had significantly lower PNRS (Cohen's = -0.318, robust = 5.5 × 10) than those with persistent ADHD (age 7-19). The PNRS, however, did not mediate polygenic risk for ADHD. Brain-wide connectivity was robustly associated with ADHD symptoms in two independent cohorts, providing further evidence of widespread dysconnectivity in ADHD. Evaluation in enriched samples demonstrates the promise of the PNRS approach for improving reproducibility in neuroimaging studies and unraveling the complex relationships between brain connectivity and behavioral disorders.
识别与注意力缺陷多动障碍（ADHD）相关的可复制神经影像学标志物受到样本量小、效应小以及方法异质性的阻碍。鉴于 ADHD 与广泛分布的大脑网络改变以及个体大脑特征的小效应有关，因此需要从全脑角度关注累积效应。使用大型多站点样本对于提高大脑磁共振成像关联研究的可重复性和临床实用性至关重要。为了解决这个问题，我们构建并验证了一种多神经风险评分（PNRS），该评分代表与 ADHD 相关的全脑静息态功能连接的累积效应，使用来自青少年大脑认知发展（ABCD，n=5543，51.5%为女性）研究的数据进行构建和验证，并在独立的俄勒冈州 ADHD-1000 病例对照队列（n=553，37.4%为女性）中进一步进行测试。在考虑了相关协变量后，ADHD PNRS 在两个队列中均与 ADHD 症状显著相关（<0.001）。最具预测性的 PNRS 涉及所有大脑网络，尽管最强的效应集中在默认模式和扣带-顶叶网络中。在纵向的俄勒冈州 ADHD-1000 研究中，非 ADHD 青少年的 PNRS 明显低于持续患有 ADHD 的青少年（Cohen's d=-0.318，robust = 5.5×10）。然而，PNRS 不能介导 ADHD 的多基因风险。在两个独立的队列中，全脑连接与 ADHD 症状显著相关，这为 ADHD 中广泛的连接障碍提供了进一步的证据。在富集样本中的评估表明，PNRS 方法在提高神经影像学研究的可重复性和揭示大脑连接与行为障碍之间复杂关系方面具有广阔的前景。
