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

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 ) Val 158 Met 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 Val 158 Met 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 COMT 158 Met 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.

COMT Val/Met and Psychopathic Traits in Children and Adolescents: A Systematic Review and New Evidence of a Developmental Trajectory toward Psychopathy

“…The gene-environment interaction has also been studied by Nobile et al [41], where they demonstrated that adolescents with the Val/Val genotype and low SES exhibit significantly higher scores on attention deficit/hyperactivity problems. On the other hand, a recent study by Abraham et al [60] demonstrated that both boys and girls with at least one copy of the Met allele were more susceptible to being affected by early life adversities and express hyperactivity and impulsivity symptoms [60]. In both studies, Val158Met did not have a significant main effect on the hyperactivity and impulsivity scores.…”

“…Ethnicity may also influence the association between Val158Met and psychopathic traits in youth, where African American participants show an increased chance of having the Val/Val genotype when compared with White participants [60]. Another study with a sample composed of 88% European Caucasian, and 22% African Canadian and mixed ancestry participants, only the European subgroup showed a significant association between Val158Met and CU scores, when the whole population did not [54].…”

“…As the systematic review solely focused on youth, there were not many results that indicated change over time. However, a study showed that, even though the main effect of Val158Met on ADHD symptoms was not significant in early childhood, it became significant in middle childhood, where children with one copy of the Met allele had a higher risk of exhibiting ADHD symptoms than Val/Val carriers [60], indicating the importance of age and development in this area of research.…”

“…Previous review articles have focused on the association of different candidate genes [58], and there has been limited focus in the literature on COMT [59], with no review on the role of COMT on psychopathic traits focusing on youth. Moreover, the changing effects of certain genes on psychopathic traits from childhood to adolescence [27], a change in the effects of COMT on ADHD from early childhood to middle childhood [60], and the dynamic nature of the COMT gene's contribution to executive functioning from childhood to adolescence [50] point to a differential effect of Val158Met on psychopathic traits during development. While the changing effects of Val158Met have been demonstrated on different phenotypes [48,49], no research has been performed on the effects of Val158Met on psychopathic traits through development from childhood to adolescence.…”

“…For youth with a diagnosed behavioral disorder, while the majority of studies showed the increased risk with the Val/Val genotype [74], three studies demonstrated the risk with the Met allele carriers [76][77][78] and three studies did not have any significant associations. Furthermore, ethnicity may also play a role in the association given the fact that genotype distribution varies across different ethnicities [60], and a European subgroup showed a significant association while the whole population did not [54].…”