Attention-deficit hyperactivity disorder (ADHD) is among the most commonly diagnosed psychiatric disorders of childhood. The dopaminergic system has been shown to have substantial effects on its etiology, with both functional Catechol-O-methyltransferase (COMT) Val¹⁵⁸Met genotype and early-life environmental adversity involved in the risk of inattention and hyperactivity/impulsivity symptoms. In this prospective longitudinal study, we examined for the first time the impact of proximal and distal early-life family adversity and COMT Val¹⁵⁸Met polymorphism gene – both the direct and the interactive effects, on children’s ADHD symptoms across childhood. Data came from the Family Life Project, a prospective longitudinal study of 1,292 children and families in high poverty from birth to 11 years. In infancy, data regarding socioeconomic (SES)-risk-factors, observed-caregiving behaviors, and DNA genotyping were collected. In early and middle childhood teachers rated the occurrence and severity of the child’s ADHD symptoms. Multilevel growth curve models revealed independent effects of COMT, early-life SES-risk and negative caregiving on ADHD symptoms in early and middle childhood. Significant gene-environment interactions were found, indicating that overall, carriers of at least one COMT¹⁵⁸Met allele were more sensitive to early-life adversity, showing higher inattention and hyperactivity/impulsivity symptoms severity in childhood when exposed to high SES-risk factors in infancy, compared to Val-Val carriers. Findings provide new insights into the complex etiology of ADHD and underline the need for further investigation of the neuronal mechanisms underlying gene-environment interactions. Findings might have implications for prevention and intervention strategies with a focus on early-life family relationships in genetically at-risk children.

注意力缺陷多动障碍（ADHD）是最常见的儿童期精神疾病之一。多巴胺能系统已被证明对其病因有重大影响，功能性儿茶酚-氧-甲基转移酶（ COMT ） Val ¹⁵⁸蛋氨酸基因型和早年环境逆境与注意力不集中和多动/冲动症状的风险有关。在这项前瞻性纵向研究中，我们首次研究了近端和远端早期家庭逆境的影响和COMT Val ¹⁵⁸蛋氨酸多态性基因——对整个童年时期儿童多动症症状的直接影响和交互影响。数据来自家庭生活项目，这是一项对 1,292 名从出生到 11 岁的高度贫困儿童和家庭进行的前瞻性纵向研究。在婴儿期，收集了有关社会经济 (SES) 风险因素、观察到的照顾行为和 DNA 基因分型的数据。在儿童早期和中期，教师对儿童多动症症状的发生和严重程度进行评估。多层次增长曲线模型揭示了COMT 、早期SES风险和对儿童早期和中期ADHD症状的消极照顾。发现了显着的基因-环境相互作用，表明总体上，至少一种基因的携带者COMT ¹⁵⁸满足与 Val-Val 携带者相比，Val-Val 等位基因对生命早期的逆境更加敏感，当在婴儿期暴露于高 SES 风险因素时，儿童时期表现出更高的注意力不集中和多动/冲动症状。 研究结果为 ADHD 的复杂病因学提供了新的见解，并强调需要进一步研究基因与环境相互作用背后的神经元机制。研究结果可能对预防和干预策略产生影响，重点关注遗传风险儿童的早期家庭关系。