Catechol-O-methyltransferase Val158Met Genotype and Early-Life Family Adversity Interactively Affect Attention-Deficit Hyperactivity Symptoms Across Childhood.

Eyal Abraham,Marc A Scott,Clancy Blair

doi:10.3389/fgene.2020.00724

Abstract

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.

Highlights

Attention-deficit hyperactivity disorder (ADHD) is one of the most prevalent childhood-onset neurodevelopmental disorders, affecting approximately 7% of children and adolescents (Thomas et al, 2015)
Protecting Against False Discovery We considered controlling for false discovery (FDR) in the eight reported effects using the work of Benjamini and Hochberg (1995), which inflates the p-values in a manner similar to Bonferroni adjustment but is more calibrated
Pearson X2 statistics were used to analyze the association between child COMT genotype and other categorical variables, and multiple regression analyses were used to examine the association between genotype and continuous variables (SESrisk and negative caregiving)

Summary

Introduction

Attention-deficit hyperactivity disorder (ADHD) is one of the most prevalent childhood-onset neurodevelopmental disorders, affecting approximately 7% of children and adolescents (Thomas et al, 2015). ADHD is a complex and heterogeneous disorder, and its etiology is not yet completely understood (Nigg, 2012). Both genetic and environmental studies of ADHD implicate catecholamines in its etiology, mainly the neurotransmitter dopamine (DA). Not all children exposed to adverse and stressful experiences show signs of ADHD symptoms. This heightens the need for research to focus on individual difference factors, including genetic variation and its interaction with environmental factors, to understand heterogeneity in response to early-life adversity (Caspi et al, 2010)

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