Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Hum Brain Mapp. 2022 Oct 15;43(15):4664-4675. doi: 10.1002/hbm.25981. Epub 2022 Jul 4.
Prior studies suggest that methylphenidate, the primary pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), alters functional brain connectivity. As the neurotransmitter systems targeted by methylphenidate undergo significant alterations throughout development, the effects of methylphenidate on functional connectivity may also be modulated by age. Therefore, we assessed the effects of a single methylphenidate challenge on brain network connectivity in stimulant-treatment naïve children and adults with ADHD. We obtained resting-state functional MRI from 50 boys (10-12 years of age) and 49 men (23-40 years of age) with ADHD (DSM IV, all subtypes), before and after an oral challenge with 0.5 mg/kg methylphenidate; and from 11 boys and 12 men as typically developing controls. Connectivity strength (CS), eigenvector centrality (EC), and betweenness centrality (BC) were calculated for the striatum, thalamus, dorsal anterior cingulate cortex (dACC), and prefrontal cortex (PFC). In line with our hypotheses, we found that methylphenidate decreased measures of connectivity and centrality in the striatum and thalamus in children with ADHD, but increased the same metrics in adults with ADHD. Surprisingly, we found no major effects of methylphenidate in the dACC and PFC in either children or adults. Interestingly, pre-methylphenidate, participants with ADHD showed aberrant connectivity and centrality compared to controls predominantly in frontal regions. Our findings demonstrate that methylphenidate's effects on connectivity of subcortical regions are age-dependent in stimulant-treatment naïve participants with ADHD, likely due to ongoing maturation of dopamine and noradrenaline systems. These findings highlight the importance for future studies to take a developmental perspective when studying the effects of methylphenidate treatment.
先前的研究表明，哌醋甲酯（治疗注意力缺陷多动障碍（ADHD）的主要药物）可改变大脑功能连接。由于哌醋甲酯靶向的神经递质系统在整个发育过程中发生重大变化，因此，哌醋甲酯对功能连接的影响也可能受到年龄的调节。因此，我们评估了单剂量哌醋甲酯对未经兴奋剂治疗的 ADHD 儿童和成人的大脑网络连接的影响。我们从 50 名男孩（10-12 岁）和 49 名男性（23-40 岁）ADHD 患者（DSM-IV，所有亚型）中获得了静息状态功能磁共振成像，在接受 0.5mg/kg 哌醋甲酯口服挑战前后；并从 11 名男孩和 12 名男性作为典型的发育对照中获得了功能磁共振成像。我们计算了纹状体、丘脑、背侧前扣带回皮层（dACC）和前额叶皮层（PFC）的连接强度（CS）、特征向量中心度（EC）和介数中心度（BC）。根据我们的假设，我们发现，哌醋甲酯降低了 ADHD 儿童纹状体和丘脑的连接和中心度，但增加了 ADHD 成人的相同指标。令人惊讶的是，我们在儿童或成人的 dACC 和 PFC 中均未发现哌醋甲酯的主要影响。有趣的是，在接受哌醋甲酯治疗之前，ADHD 患者与对照组相比，连接和中心度主要在前额叶区域出现异常。我们的研究结果表明，在未经兴奋剂治疗的 ADHD 患者中，哌醋甲酯对皮质下区域连接的影响具有年龄依赖性，这可能是由于多巴胺和去甲肾上腺素系统的持续成熟。这些发现强调了未来研究在研究哌醋甲酯治疗效果时采取发展观点的重要性。
