Abraham Eyal, Scott Marc A, Blair Clancy
Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States.
Division of Translational Epidemiology, New York State Psychiatric Institute, New York, NY, United States.
Front Genet. 2020 Jul 10;11:724. doi: 10.3389/fgene.2020.00724. eCollection 2020.
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--methyltransferase () 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 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 , 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 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)是儿童期最常被诊断出的精神疾病之一。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-O-甲基转移酶(COMT)基因型和早期生活环境逆境都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以及COMT基因多态性——直接和交互作用,对儿童期ADHD症状的影响。数据来自家庭生活项目,这是一项对1292名出生至11岁处于高贫困状态的儿童及其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、观察到的养育行为和DNA基因分型的数据。在儿童早期和中期,教师对儿童ADHD症状的发生情况和严重程度进行了评分。多层次生长曲线模型揭示了COMT、早期生活SES风险和负面养育对儿童早期和中期ADHD症状的独立影响。发现了显著的基因-环境相互作用,表明总体而言,至少携带一个Met等位基因的携带者对早期生活逆境更敏感,与Val-Val携带者相比,在婴儿期暴露于高SES风险因素时,在儿童期表现出更高的注意力不集中和多动/冲动症状严重程度。研究结果为ADHD的复杂病因提供了新的见解,并强调需要进一步研究基因-环境相互作用背后的神经机制。研究结果可能对以遗传风险儿童的早期家庭关系为重点的预防和干预策略有启示意义。