Synaptosomal-Associated Protein 25 Gene Polymorphisms Affect Treatment Efficiency of Methylphenidate in Children With Attention-Deficit Hyperactivity Disorder: An fNIRS Study.

Jie Li,Yi-Wen Zhang,Xin-Xin Tian,Wen-Jie Yan,Yan Wu

doi:10.3389/fnbeh.2021.793643

Abstract

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 (SNAP-25) gene MnlI polymorphisms may be related to the efficacy of MPH. However, the association between SNAP-25MnlI 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 SNAP-25 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 SNAP-25 gene MnlI 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-MPH1.5h) and 4 weeks (post-MPH4w) of MPH treatments were monitored using fNIRS during the go/no-go task. SNAP-IV scores were evaluated both pre-MPH and post-MPH4w treatments. In the T/T genotype group, [Δavg oxy-Hb] in the dorsolateral prefrontal cortex was significantly higher after 4 weeks of MPH (post-MPH4W) 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-MPH4w 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-MPH1.5h, and post-MPH4w 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 SNAP-25 MnlI polymorphism analysis may be a useful biomarker for evaluating the effects of MPH in children with ADHD.

Highlights

Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by persistent inattention, hyperactivity, and impulsivity (Posner et al, 2020)
The decreased expression of synaptosomal-associated protein 25 (SNAP-25) mRNA and protein in model mice lacking SNAP-25 (50% lower than that in wild-type mice) leads to symptoms of hyperactivity (Corradini et al, 2009), and the transgenic repair of SNAP-25 function restores normal dopaminergic transmission (Steffensen et al, 1999). These findings suggest that the SNAP-25 gene may underpin hyperactive behavior
This study employed near-infrared spectroscopy imaging technology combined with the detection of SNAP-25 gene MnlI polymorphisms to explore the relationship between SNAP-25 gene MnlI polymorphisms and changes in brain function after

Summary

Introduction

Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by persistent inattention, hyperactivity, and impulsivity (Posner et al, 2020). ADHD is associated with functional deficits in children, including poor interpersonal relationships (especially parentchild and sibling relationships), poor academic performance, low self-evaluation, and negative emotions. ADHD symptoms can persist into adulthood, which can negatively impact the patient’s physical and mental health, family life, and social skills in adulthood (Banaschewski et al, 2017). The global prevalence of ADHD in children and adolescents is ∼6.29% (Posner et al, 2020). ADHD symptoms are associated with alterations in the prefrontal cortex (PFC) and subcortical areas and are thought to be underscored by impaired neurotransmission and insufficient catecholamine production. Approved first-line drug therapies for the treatment of ADHD include psychostimulants, such as amphetamine and methylphenidate (MPH). Tomoxetine is the first non-stimulant drug approved for treating ADHD. Considerable inter-individual differences exist in clinical results, optimal drug dosages, and duration of effects, which may reflect genetic effects

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