Neurobehavioral Clinical Research Section, Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
National Institute of Mental Health, Bethesda, MD, 20892, USA.
Transl Psychiatry. 2022 Sep 9;12(1):378. doi: 10.1038/s41398-022-02139-x.
Attention-deficit/hyperactivity disorder (ADHD) is associated with a wide array of neural and cognitive features, and other psychiatric disorders, identified mainly through cross-sectional associations studies. However, it is unclear if the disorder is causally associated with these neurocognitive features. Here, we applied a two-sample bidirectional Mendelian randomization (MR) study to summary GWAS data to explore the presence and direction of a causal effect between ADHD and a range of neurocognitive features and other psychiatric disorders. The inverse variance weighted method was used in the main analysis, and two MR methods (MR-Egger, weighted median) were used for robustness checks. We found that genetic risk for ADHD was causally associated with a decreased area of lateral orbitofrontal cortex. Conversely, we found that brain volume and some features of intrinsic functional connectivity had causal effects on ADHD risk. Bidirectional causal links were found between ADHD and adult general intelligence, as well as depression and autistic spectrum disorders. Such work highlights the important ties between ADHD and general cognitive ability, and suggest some neural features, previously merely associated with the disorder, may play a causal role in its pathogenesis.
注意缺陷多动障碍（ADHD）与广泛的神经和认知特征以及其他精神疾病有关，这些主要是通过横断面关联研究确定的。然而，目前尚不清楚该疾病是否与这些神经认知特征存在因果关系。在这里，我们应用两样本双向孟德尔随机化（MR）研究，对汇总的 GWAS 数据进行分析，以探讨 ADHD 与一系列神经认知特征和其他精神疾病之间是否存在因果关系。主要分析采用逆方差加权法，并用两种 MR 方法（MR-Egger、加权中位数）进行稳健性检验。我们发现 ADHD 的遗传风险与外侧眶额皮层面积减小有关。相反，我们发现大脑体积和内在功能连接的某些特征对 ADHD 风险有因果影响。ADHD 与成人一般智力之间以及抑郁和自闭症谱系障碍之间存在双向因果关系。这项工作突出了 ADHD 与一般认知能力之间的重要联系，并表明一些先前仅与该疾病相关的神经特征可能在其发病机制中起因果作用。
