Supplementary Material for: Addressing emotional dysregulation and potential pharmacogenetic implication of 5-HTTLPR genotype in ADHD

This review unpacks the emotional presentation of externalizing behaviors in attention deficit hyperactivity disorder (ADHD), by diving into the psychophysiology, neurophysiology and neurogenetics in relation to executive function. The correlations among these three variables are identified, showing that standard assessments for ADHD leaves out the emotional dysregulation element. This may lead to suboptimal management outcomes during the development progression into adolescence and adulthood. The emotional impulsivity manifestation in adolescence and adulthood related to the under-managed emotional dysregulation in childhood is found to be associated with subtle confounding impact of 5-HTTLPR genotype. The genotype of interest affects the neurochemistry, neurophysiology and psychophysiology of the cognition for executive function. The established practice of using methylphenidate in treating ADHD, surprisingly has a neurogenetic effect in targeting the genotype of interest. Methylphenidate provides neuroprotective effects throughout the neurodevelopment timeline from childhood to adulthood. The emotional dysregulation element in ADHD which is often overlooked should be addressed to improve the prognostic outcomes in adolescence and adulthood.本综述深入剖析注意缺陷多动障碍（attention deficit hyperactivity disorder）中外化行为的情绪表现，围绕与执行功能相关的心理生理学、神经生理学及神经遗传学展开系统探讨。研究明确了上述三类变量间的关联，同时发现当前ADHD的标准评估手段遗漏了情绪失调这一核心维度。这一疏漏可能在患儿从儿童期向青春期乃至成年期的病程进展中，导致干预效果未达最优。研究还发现，儿童期情绪失调未得到妥善管控所引发的青春期及成年期情绪冲动表现，与5-HTTLPR基因型所带来的细微混杂效应存在关联。该目标基因型会对执行功能相关认知的神经化学、神经生理学及心理生理学特征产生影响。令人意外的是，当前临床治疗ADHD的常规用药哌甲酯，在靶向该目标基因型时可发挥神经遗传效应。哌甲酯可在从儿童期至成年期的全神经发育周期中，发挥神经保护作用。ADHD中常被忽视的情绪失调维度，应当被纳入临床关注范畴，以改善患者青春期及成年期的预后结局。