Li Jie, Yan Wen-Jie, Wu Yan, Tian Xin-Xin, Zhang Yi-Wen
Department of Developmental and Behavioral Pediatrics, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Pediatrics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.
Front Behav Neurosci. 2022 Jan 5;15:793643. doi: 10.3389/fnbeh.2021.793643. eCollection 2021.
Methylphenidate (MPH) is the first-line drug for the treatment of children with attention-deficit hyperactivity disorder (ADHD); however, individual curative effects of MPH vary. Many studies have demonstrated that synaptosomal-associated protein 25 () gene I polymorphisms may be related to the efficacy of MPH. However, the association between I polymorphisms and changes in brain hemodynamic responses after MPH treatment is still unclear. This study used functional near-infrared spectroscopy (fNIRS) to preliminarily investigate the interaction of MPH treatment-related prefrontal inhibitory functional changes with the genotype status of the gene in children with ADHD. In total, 38 children with ADHD aged 6.76-12.08 years were enrolled in this study and divided into the following two groups based on gene I polymorphisms: T/T genotype group (wild-type group, 27 children) and G allele carrier group (mutation group, 11 children). The averaged oxygenated hemoglobin concentration changes [Δavg oxy-Hb] and deoxyhemoglobin concentration changes [Δavg deoxy-Hb] in the frontal cortex before MPH treatment and after 1.5 h (post-MPH) and 4 weeks (post-MPH) of MPH treatments were monitored using fNIRS during the go/no-go task. SNAP-IV scores were evaluated both pre-MPH and post-MPH treatments. In the T/T genotype group, [Δavg oxy-Hb] in the dorsolateral prefrontal cortex was significantly higher after 4 weeks of MPH (post-MPH) treatment than pre-treatment; however, in the G allele group, no significant differences in [Δavg oxy-Hb] were observed between pre- and post-treatments. In the go/no-go task, the accuracy was significantly increased post-MPH treatment in the T/T genotype group, while no significant differences were observed in response time and accuracy of the "go" sand no-go task in the G allele group for pre-MPH, post-MPH, and post-MPH treatments. The T/T genotype group exhibited a significant decrease in SNAP-IV scores after MPH treatment, while the G allele group showed no significant difference. In conclusion, fNIRS data combined with I polymorphism analysis may be a useful biomarker for evaluating the effects of MPH in children with ADHD.
哌甲酯（MPH）是治疗儿童注意力缺陷多动障碍（ADHD）的一线药物；然而，MPH的个体疗效存在差异。许多研究表明，突触体相关蛋白25（）基因I多态性可能与MPH的疗效有关。然而，I多态性与MPH治疗后脑血流动力学反应变化之间的关联仍不清楚。本研究使用功能近红外光谱（fNIRS）初步探讨MPH治疗相关的前额叶抑制性功能变化与ADHD儿童基因的基因型状态之间的相互作用。本研究共纳入38名年龄在6.76 - 12.08岁的ADHD儿童，并根据基因I多态性将其分为以下两组：T/T基因型组（野生型组，27名儿童）和G等位基因携带者组（突变组，11名儿童）。在执行停止信号任务期间，使用fNIRS监测MPH治疗前、治疗1.5小时后（MPH后）和治疗4周后（MPH后）额叶皮质中平均氧合血红蛋白浓度变化[Δavg oxy-Hb]和脱氧血红蛋白浓度变化[Δavg deoxy-Hb]。在MPH治疗前和治疗后均评估SNAP-IV评分。在T/T基因型组中，MPH治疗4周后（MPH后）背外侧前额叶皮质的[Δavg oxy-Hb]显著高于治疗前；然而，在G等位基因组中，治疗前后[Δavg oxy-Hb]未观察到显著差异。在停止信号任务中，T/T基因型组MPH治疗后准确性显著提高，而G等位基因组在MPH治疗前、MPH后和MPH后治疗的“执行”和“停止”任务的反应时间和准确性未观察到显著差异。T/T基因型组MPH治疗后SNAP-IV评分显著降低，而G等位基因组无显著差异。总之，fNIRS数据结合I多态性分析可能是评估MPH对ADHD儿童疗效的有用生物标志物。
