Department of Psychology, Georgetown University, Washington, DC, USA.
Children's Research Institute, Children's National Medical Center, Washington, DC, USA.
Transl Psychiatry. 2024 Nov 6;14(1):463. doi: 10.1038/s41398-024-03165-7.
Widely prescribed for Attention-Deficit/Hyperactivity Disorder (ADHD), stimulants (e.g., methylphenidate) have been studied for their chronic effects on the brain in prospective designs controlling dosage and adherence. While controlled approaches are essential, they do not approximate real-world stimulant exposure contexts where medication interruptions, dosage non-compliance, and polypharmacy are common. Brain changes in real-world conditions are largely unexplored. To fill this gap, we capitalized on the observational design of the Adolescent Brain Cognitive Development (ABCD) study to examine effects of stimulants on large-scale bilateral cortical networks' resting-state functional connectivity (rs-FC) with 6 striatal regions (left and right caudate, putamen, and nucleus accumbens) across two years in children with ADHD. Bayesian hierarchical regressions revealed associations between stimulant exposure and change in rs-FC of multiple striatal-cortical networks, affiliated with executive and visuo-motor control, which were not driven by general psychotropic medication. Of these connections, three were selective to stimulants versus stimulant naive: reduced rs-FC between caudate and frontoparietal network, and between putamen and frontoparietal and visual networks. Comparison with typically developing children in the ABCD sample revealed stronger rs-FC reduction in stimulant-exposed children for putamen and frontoparietal and visual networks, suggesting a normalizing effect of stimulants. 14% of stimulant-exposed children demonstrated reliable reduction in ADHD symptoms, and were distinguished by stronger rs-FC reduction between right putamen and visual network. Thus, stimulant exposure for a two-year period under real-world conditions modulated striatal-cortical functional networks broadly, had a normalizing effect on a subset of networks, and was associated with potential therapeutic effects involving visual attentional control.
广泛用于治疗注意力缺陷多动障碍（ADHD）的兴奋剂（例如哌醋甲酯）已在前瞻性设计中进行了研究，以控制剂量和依从性来研究其对大脑的慢性影响。虽然控制方法是必要的，但它们并不能模拟现实世界中兴奋剂暴露的情况，在这些情况下，药物中断、剂量不依从和多药治疗很常见。现实条件下大脑的变化在很大程度上仍未得到探索。为了填补这一空白，我们利用青少年大脑认知发展（ABCD）研究的观察设计，检查了兴奋剂对 ADHD 儿童两年内 6 个纹状体区域（左侧和右侧尾状核、壳核和伏隔核）与大尺度双侧皮质网络静息态功能连接（rs-FC）的影响。贝叶斯层次回归显示，兴奋剂暴露与 rs-FC 的多个纹状体-皮质网络变化之间存在关联，这些网络与执行和视觉运动控制有关，而与一般精神药物无关。在这些连接中，有三个是兴奋剂与兴奋剂未治疗组之间的选择性连接：尾状核与额顶叶网络之间以及壳核与额顶叶和视觉网络之间的 rs-FC 减少。与 ABCD 样本中的典型发育儿童进行比较显示，在兴奋剂暴露的儿童中，纹状体和额顶叶和视觉网络的 rs-FC 减少更强，这表明兴奋剂具有正常化作用。14%的兴奋剂暴露儿童表现出 ADHD 症状的可靠减少，并且与右侧壳核和视觉网络之间 rs-FC 减少更强有关。因此，在现实条件下进行为期两年的兴奋剂暴露调节了广泛的纹状体-皮质功能网络，对一部分网络具有正常化作用，并与涉及视觉注意力控制的潜在治疗效果相关。
