Effects of Childhood Adversity and Its Interaction with the MAOA, BDNF, and COMT Polymorphisms on Subclinical Attention Deficit/Hyperactivity Symptoms in Generally Healthy Youth.

Meng-Che Tsai,Yi-Ping Hsieh,Kai-Jyun Jhang,Carol Strong,Chung-Ying Lin,Yu-Fang Lin,Chih-Ting Lee,Yi-Ching Lin

doi:10.3390/children7090122

Abstract

We aimed to investigate the effects of childhood adversity and its interaction with the polymorphisms in the monoamine oxidase A (MAOA), brain-derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) genes on attention and hyperactivity disorder (ADHD) symptoms in a community sample of generally healthy youth. Participants (N = 432) completed questionnaires assessing ADHD symptoms (i.e., inattention, hyperactivity, and impulsiveness) and adverse childhood experiences, such as adverse environments (AEs) and childhood maltreatment (CM). Salivary genomic DNA was used to test polymorphisms in MAOA, BDNF, and COMT genes. A gene score (GS) was created based on the number of risk allele in the studied genes. Multiple linear regressions were used to examine the genetic and environmental effects on ADHD symptoms. The univariate analysis indicated that CM was significantly associated with inattention (β = 0.48 [95% confidence interval 0.16–0.79]), hyperactivity (0.25 [0.06–0.45]), and impulsiveness (1.16 [0.26–2.05]), while the GS was associated with hyperactivity (0.22 [0.11–0.33]) and impulsiveness (0.56 [0.06–1.05]). Only the GS remained significantly associated with hyperactivity (0.25 [0.12–0.37]) and impulsiveness (0.79 [0.20–1.38]) when the gene-environment interaction term was added in the model. No effects were found for AE and the gene-environment interaction term. In conclusion, CM was associated with ADHD symptoms in emerging adulthood. Genetic factors may also play a significant role in the association with these outcomes.

Highlights

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that has heterogeneity in its etiology [1]
The C allele in the brain-derived neurotrophic factor (BDNF) polymorphism was consistently associated with hyperactivity in the dominant (β = 0.38, [0.06, 0.71]), recessive
As for the A allele in the COMT polymorphism, a negative association was found in the link to hyperactivity in the dominant (β = −0.36, [−0.64, −0.07]) and additive models (β = −0.24, [−0.45, −0.03])

Summary

Introduction

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that has heterogeneity in its etiology [1]. Prior research has demonstrated etiological heterogeneity in terms of multiple genetic and environmental risk factors that might interact with each other and result in the diverse cognitive and behavioral trajectories of the disorder through a complex developmental neural mechanism [2]. ADHD has long been thought of as having an early onset in childhood and continuing into adolescence in some affected individuals, and it is required that symptoms must be present before the age of 12 years, in order to fulfill criteria for a diagnosis of ADHD. Accumulative evidence raises the possibility that ADHD symptomatology emerging in young adulthood may be distinct from a diagnosis of ADHD itself and represent a distinctive entity, though this distinction is not currently clear, nor is the difference between the short-and long-term impact of having an ADHD diagnosis versus symptoms that requires further research and clinical attention [4]. Compared to the majority of research attention paid to child cohorts, studies dedicated to the emerging ADHD symptoms in young adults are relatively scarce

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