Infant Predictors of School-Age ADHD Symptoms in Siblings at High Familial Risk for ASD

Background:   Many children with autism spectrum disorder (ASD) also have symptoms of attention-deficit/hyperactivity disorder (ADHD), a developmental disorder characterised by impairing inattentiveness, hyperactivity, and impulsivity. The high co-occurrence rate, combined with evidence that ASD and ADHD share genetic and neurobiological pathways, suggests that infants who are at high familial risk for ASD may also be at increased genetic vulnerability to developing ADHD. Since ADHD is associated with significant school, social, emotional and behavioural problems, it is crucial to understand the development of ADHD in high-risk infants and, ideally, identify predictors of these symptoms early in life to facilitate timely intervention. 

Objectives:   The objectives were first, to assess school-age levels of ADHD symptoms in high-risk children prospectively studied since the first year of life, and second, to identify infant and early-life characteristics associated with school-age ADHD outcomes. 

Methods: 42 infants with an older sibling with ASD (high-risk infants) and 37 infants with typically developing older sibling/s (low-risk infants) were enrolled in a prospective longitudinal study and completed assessments at 7-, 14-, 24-, 36- months and 7 years of age.  At 7 years, parent-rated ADHD symptoms on the Conners 3 were compared between high-risk children who met DSM-5 criteria for ASD (HR-ASD; n = 15), high-risk children without ASD (HR-No ASD; n = 27) and low-risk controls (LR; n = 37).  Early life (< 3 years) neurocognitive characteristics that were predictive of school-age ADHD symptoms in high-risk children were explored. Predictors were selected based on their robust association with ADHD in the literature. These were: saccadic RT and reaction time variability (RTV) measured at 7m, 14m and 36m on an attention shifting task, cognitive control performance (RT) on a Spatial Conflict task at 36m, and the temperament factors Surgency, Negative Affect, and Effortful Control measured at 7m, 14m, 24m, and 36m.  

 Results: 7-year ADHD symptoms were significantly higher in HR-ASD than HR-No ASD (p < .05, d = .79) and LR (p < .01, d = 1.13), but were low and comparable in the latter two groups (p > .2).  Within the high-risk group, ADHD symptoms were significantly associated with earlier manual and saccadic RT and temperament, such that individuals with the slowest RTs and lowest Effortful Control in infancy and toddlerhood showed the highest levels of ADHD symptoms later in childhood (table 1).  When the high-risk group was divided into those with elevated ADHD symptoms at 7 (Conners 3 T-scores > 60; HR-high-ADHD) and those with typical levels of ADHD at 7 (Conners T-scores < 60; HR-low-ADHD), the HR-high-ADHD children exhibited significantly slower RTs and significantly lower Effortful Control  in infancy and toddlerhood than the HR-low-ADHD and LR control groups (figure 1).  These effects remained when covarying for ASD symptoms at 7 years.

 Conclusions:   A proportion of high-risk infants, particularly those who develop clinically significant ASD, show high levels of ADHD symptoms at school-age.  Slowed RTs and poor self-regulation in infancy and toddlerhood are associated with school-age ADHD symptoms in high-risk children, and may represent early risk-markers of later-childhood ADHD problems.