Early behavioral indices of inherited liability to autism

Abstract

Objective: The observed heterogeneity of autism spectrum disorder (ASD)-and the diversity of rare germline mutations with which it has been associated-has been difficult to reconcile with knowledge of its pronounced heritability in the population.

Methods: This article reviews and synthesizes recent family and developmental studies incorporating behavioral indices of inherited risk for ASD.

Results: Autism may arise from critical combinations of early inherited neurobehavioral susceptibilities-some specific to autism, some not-each of which may be traceable to partially-independent sets of genetic variation. These susceptibilities and their respective genetic origins may not relate to the characterizing symptoms of autism (after it develops) in a straightforward way, and may account for "missing heritability" in molecular genetic studies.

Conclusions: Within-individual aggregations of a finite set of early inherited neurobehavioral susceptibilities-each individually common in the population-may account for a significant share of the heritability of ASD. Comprehensive identification of these underlying traits my help elucidate specific early intervention targets in individual patients, especially if autism represents a developmental consequence of earlier-interacting susceptibilities. Scientific understanding of the early ontogeny of autism will benefit from epidemiologically-rigorous, genetically-informative studies of robust endophenotypic candidates whose inter-relationships in infancy are mapped and normed.

Figure 1.

Mechanisms by which genetic influences that are non-specific to autism may compound autistic severity and incur “comorbid” affectation with non-ASD-specific traits (ADHD as an example here). 1. Specific influences on ASD 2. Amplification of ASD severity by a non-ASDspecific causal influence. ADHD attention-deficit/hyperactivity disorder, ASD autism spectrum disorder. Note that in this model, inherited liabilities that are initially independent become correlated (a) by definition when contributing to the development of autism, and (b) by reciprocal interaction over the course of later development, after the respective syndromes of disability are manifest.