Peking University Sixth Hospital/Institute of Mental Health, Beijing, China.
National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University, Beijing, China.
CNS Neurosci Ther. 2021 Jun;27(6):664-673. doi: 10.1111/cns.13625. Epub 2021 Mar 16.
Inhibition deficits have been suggested to be a core cognitive impairment in attention-deficit/hyperactivity disorder (ADHD). Exploring imaging patterns and the potential genetic components associated with inhibition deficits would definitely promote our understanding of the neuropathological mechanism of ADHD. This study aims to investigate the multimodal imaging fusion features related to inhibition deficits in adults with ADHD (aADHD) and to make an exploratory analysis of the role of inhibition-related gene, NOS1, on those brain alterations.
Specifically, multisite canonical correlation analysis with reference plus joint independent component analysis (MCCAR + jICA) was conducted to identify the joint co-varying gray matter volume (GMV) and the functional connectivity (FC) features related to inhibition in 69 aADHD and 44 healthy controls. Then, mediation analysis was employed to detect the relationship among inhibition-related imaging features, NOS1 ex1f-VNTR genotypes, and inhibition.
Inhibition-directed multimodal imaging fusion patterns of aADHD were reduced GMV and FC in inhibition network and increased GMV and FC in default mode network. The results showed a significant indirect effect of NOS1 ex1f-VNTR on inhibition via FC component [effect size = -0.54 (SE = 0.29), 95% CI = -1.16 to -0.01]. In addition, the results indicated a significant indirect effect of GMV on the inhibition via FC component [effect size = 0.43 (SE = 0.23), 95% CI = 0.12 to 1.00].
The findings suggested that reduced GMV and FC in inhibition network and increased GMV and FC in default mode network were jointly responsible for inhibition deficits in aADHD. Both the NOS1 ex1f-VNTR genotypes and GMV might influence the inhibition through the mediation effect of the aforementioned FC (NOS1/GMV Inhibition).
抑制缺陷被认为是注意力缺陷多动障碍（ADHD）的核心认知障碍。探索与抑制缺陷相关的成像模式和潜在遗传成分肯定会促进我们对 ADHD 神经病理学机制的理解。本研究旨在调查与 ADHD 成人（aADHD）抑制缺陷相关的多模态成像融合特征，并对抑制相关基因 NOS1 对这些大脑改变的作用进行探索性分析。
具体而言，采用参考加联合独立成分分析（MCCAR + jICA）的多站点典型相关分析，以识别与抑制相关的灰质体积（GMV）和功能连接（FC）特征在 69 名 aADHD 和 44 名健康对照者中的共同变化。然后，采用中介分析来检测抑制相关的成像特征、NOS1 ex1f-VNTR 基因型与抑制之间的关系。
aADHD 的抑制定向多模态成像融合模式表现为抑制网络的 GMV 和 FC 降低，默认模式网络的 GMV 和 FC 增加。结果显示，NOS1 ex1f-VNTR 通过 FC 成分对抑制的显著间接效应[效应量=-0.54（SE=0.29），95%置信区间=-1.16 至-0.01]。此外，结果表明 GMV 通过 FC 成分对抑制的显著间接效应[效应量=0.43（SE=0.23），95%置信区间=0.12 至 1.00]。
研究结果表明，抑制网络中的 GMV 和 FC 降低以及默认模式网络中的 GMV 和 FC 增加共同导致了 aADHD 的抑制缺陷。NOS1 ex1f-VNTR 基因型和 GMV 均可能通过上述 FC（NOS1/GMV 抑制）的中介作用影响抑制。
