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.

本综述剖析注意缺陷多动障碍（attention deficit hyperactivity disorder，简称ADHD）中外化行为的情绪表现，深入探讨与执行功能相关的心理生理学、神经生理学及神经遗传学机制。研究明确了上述三类变量间的关联，并揭示当前ADHD标准化评估手段均未纳入情绪失调这一核心维度。这一疏漏可能导致患者在步入青春期及成年阶段后，其临床管理效果难以达到最优。研究发现，青春期与成年期出现的情绪冲动性表现，与儿童时期未得到有效管控的情绪失调存在相关性，且该关联受到5-羟色胺转运体基因（5-HTTLPR）的细微混杂影响。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调控作用。令人意外的是，当前临床治疗ADHD的常规用药哌甲酯（methylphenidate），可通过靶向该目标基因型发挥神经遗传学效应。哌甲酯可在从儿童期至成年期的完整神经发育进程中发挥神经保护作用。ADHD中常被忽视的情绪失调维度亟待得到重视与干预，以改善患者在青春期及成年期的预后效果。