Genetic and Environmental Influences on the Developmental Course of Attention-Deficit/Hyperactivity Disorder Symptoms From Childhood to Adolescence

Abstract

Importance Attention-deficit/hyperactivity disorder (ADHD) is conceptualized as a neurodevelopmental disorder that is strongly heritable. However, to our knowledge, no study to date has examined the genetic and environmental influences explaining interindividual differences in the developmental course of ADHD symptoms from childhood to adolescence (ie, systematic decreases or increases with age). The reason ADHD symptoms persist in some children but decline in others is an important concern, with implications for prognosis and interventions. Objective To assess the proportional impact of genes and the environment on interindividual differences in the developmental course of ADHD symptom domains of hyperactivity/impulsivity and inattention between ages 8 and 16 years. Design, Setting, and Participants A prospective sample of 8395 twin pairs from the Twins Early Development Study, recruited from population records of births in England andWales between January 1, 1994, and December 31, 1996. Data collection at age 8 years took place between November 2002 and November 2004; data collection at age 16 years took place between February 2011 and January 2013. Main Outcomes and Measures Both DSM-IV ADHD symptom subscales were rated 4 times by participants’ mothers. Results Estimates from latent growth curve models indicated that the developmental course of hyperactivity/impulsivity symptoms followed a sharp linear decrease (mean score of 6.0 at age 8 years to 2.9 at age 16 years). Interindividual differences in the linear change in hyperactivity/impulsivity were under strong additive genetic influences (81%; 95% CI, 73%-88%). More than half of the genetic variation was specific to the developmental course and not shared with the baseline level of hyperactivity/impulsivity. The linear decrease in inattention symptoms was less pronounced (mean score of 5.8 at age 8 years to 4.9 at age 16 years). Nonadditive genetic influences accounted for a substantial amount of variation in the developmental course of inattention symptoms (54%; 95% CI, 8%-76%), with more than half being specific to the developmental course. Conclusions and Relevance The large genetic influences on the developmental course of ADHD symptoms are mostly specific and independent of those that account for variation in the baseline level of symptoms. Different sets of genes may be associated with the developmental course vs the baseline level of ADHD symptoms and explain why some children remit from ADHD, whereas others persist. Recent longitudinal imaging data indicate that the maintenance or increase in symptoms is underpinned by atypical trajectories of cortical development. This may reflect a specific genetic liability, distinct from that which contributes to baseline ADHD symptoms, and warrants closer follow-up.

Life Span Studies of ADHD—Conceptual Challenges and Predictors of Persistence and Outcome

“…The investigators also reported a more stable pattern of inattentive symptoms compared to hyperactive symptoms, a finding that was reported in previous studies [56]. In a different study, 8395 twin pairs were assessed for ADHD at ages 8, 12, 14, and 16 with a DSM-IV ADHD symptom subscale [57]. Consistent with population-based and clinical studies, there was a general decline of symptoms across ages, and inattentive symptoms persisted more than hyperactive/impulsive symptoms.…”

Persistence and Subtype Stability of ADHD Among Substance Use Disorder Treatment Seekers

“…ADHD is a highly heritable disorder, with data from twin studies indicating that approximately 70% to 80% of the phenotypic variability is due to genetic influences (Faraone et al, 2005; Franke et al, 2012; Todd et al, 2001) and that heritability of clinically diagnosed ADHD remains high across the life span (Larsson, Chang, D’Onofrio, & Lichtenstein, 2014). Moreover, the developmental course of ADHD appears to have a strong genetic underpinning, with evidence for a primary role of genetic factors in ADHD symptom trajectories from childhood into adolescence (Pingault et al, 2015) and a higher familial risk for persistent ADHD than for ADHD that remits by adulthood (Franke et al, 2012). …”

Review: changing (shared) heritability of ASD and ADHD across the lifespan

“…Several longitudinal twin studies on ADHD symptoms report that new, age-specific genetic effects influence ADHD symptoms in adolescence and adulthood, suggesting that ADHD symptoms are a developmentally complex phenotype characterized by both continuity and change across the life span [3,9,12,13,19]. In addition, only a modest overlap between longitudinal genetic effects underlying both symptom domains (inattention versus hyperactivity/impulsivity) appears present, suggesting it is necessary to study both separately.…”