29.1 GENETIC UNDERPINNINGS OF AUTISM SPECTRUM DISORDER

Abstract

ADHD comorbidity is extremely common in autism spectrum disorder (ASD), and the co-occurrence of traits of ASD with subclinical manifestations of ADHD extends to the general population. In this presentation, data from 4 longitudinal studies collectively involving over 1200 children will be analyzed and the results synthesized to address the issue of overlap in the genetic structure of ADHD and ASD. After considering multiple competing models for the nature of overlap, the preponderance of the available scientific evidence supports a model in which inherited liability indexed by ADHD exerts substantial causal influence on the development of ASD and predicts recurrence among the siblings of affected index cases. The notion that nonspecific insults to neural development, either inherited or acquired, might augment the impact of ASD-specific genetic susceptibilities in contributing to its cause has not been appreciated in the literature on comorbidity, and has significant implications for both personalized intervention and future research. The relationship between early childhood ADHD symptomatology and other heritable predictors of ASD occurrence (and recurrence in families), including ASD traits in first-degree relatives and measures of infant eye tracking and motor coordination, is beginning to be understood as a matrix of independent risk factors that operate jointly in raising risk for ASD. It is conceivable that early treatment of ADHD liability—before the usual onset of the characterizing symptoms of ASD in the second year of life—might ameliorate the severity of ASD syndromes. In order to test this possibility, it will be necessary to develop the technologies to ascertain and quantify ADHD liabilities with higher precision in the first year of life. Given that ADHD appears to be a common contributor to inherited liability for ASD, the statistical power of future biomarker studies, particularly in ASD genetics and neuroimaging, can be enhanced by more comprehensive attention to the measurement of ADHD traits that index causal influences on the disorder, among not only cases but also (importantly) controls.