Attention and motor deficits index non-specific background liabilities that predict autism recurrence in siblings

Abstract

BackgroundRecent research has demonstrated that subclinical autistic traits of parents amplify the effects of deleterious mutations in the causation of autism spectrum disorder (ASD) in their offspring. Here, we examined the extent to which two neurodevelopmental traits that are non-specific to ASD—inattention/hyperactivity and motor coordination—might contribute to ASD recurrence in siblings of ASD probands.MethodsData from a quantitative trait study of 114 ASD probands and their brothers, 26% of whom also had ASD, were analyzed. Autistic trait severity was ascertained using the Social Responsiveness Scale-2, attention/hyperactivity problems using the Achenbach System of Empirically Based Assessment, and motor coordination (in a subset of participants) using the Developmental Coordination Disorder Questionnaire.ResultsAmong siblings (affected and unaffected), both categorical recurrence of ASD (Nagelkerke R 2 = 0.53) and quantitative ASD trait burden (R 2 = 0.55) were predicted by sibling ADHD and motor coordination impairment scores, even though these traits, on average, were not elevated among the unaffected siblings.ConclusionsThese findings in a clinical family cohort confirm observations from general population studies that inattention/hyperactivity and motor impairment—axes of behavioral development that are non-specific to ASD, and often appreciable before ASD is typically diagnosed—jointly account for over 50% of the variation in autistic impairment of siblings, whether ascertained quantitatively or categorically. This finding within a sibling design suggests that background ASD susceptibilities that are inherited but non-specific (“BASINS”) may contribute to additive genetic liability in the same manner that ASD-specific susceptibilities (such as parental subclinical ASD traits and deleterious mutations) engender ASD risk.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-017-9212-y) contains supplementary material, which is available to authorized users.

Epilepsy and Autism Severity: A Study of 6,975 Children

“…Examples include Happé's Fractionable Autism Triad [Happe & Ronald, ] focused on the classical triad of social impairments, communicative impairments, and repetitive/restrictive behaviors and interest. Constantino's and colleagues' work demonstrates how the overlap of inherited core autism impairments, attentional impairments, and motor impairments lead to the full expression of ASD [Mous et al, ]. Both of these efforts rest on a parsing of only the cognitive aspects of ASD.…”

“…Beyond larger studies, studies that measure performance directly, and studies that sample in unbiased fashion, including from children both with and without ASD, longitudinal studies [Karmiloff‐Smith, ; Mous et al, ] and interventional studies may assist in more closely approximating causal relationships among genetic and brain‐based factors responsible for epilepsy, for regression and for the cognitive manifestations of ASD.…”

“…In addition to the “classic” severity factors of general intelligence, propositional language, and ASD‐defining core features, we also examined motor function as a possible mediator of the relationship between ASD and epilepsy. Recent work by Mous, Jiang, Agrawal, and Constantino [] has suggested that motor impairment may be specifically indicative of a key genetic contributor to ASD risk. Motor impairments have been known in ASD since Kanner's original description [Kanner, ] and are highly prevalent in the disorder [Vanvuchelen, Roeyers, & De Weerdt, ; Weimer, Schatz, Lincoln, Ballantyne, & Trauner, ].…”

“…Motor impairments have been known in ASD since Kanner's original description [Kanner, ] and are highly prevalent in the disorder [Vanvuchelen, Roeyers, & De Weerdt, ; Weimer, Schatz, Lincoln, Ballantyne, & Trauner, ]. They may be either reflective of the similar pathophysiological processes that cause the cardinal symptoms of ASD or even causally involved in the pathophysiology of the social‐communicative phenotype [Denckla, ; Ewen et al, ; Gowen & Hamilton, ; Lloyd, MacDonald, & Lord, ; Mostofsky et al, ; Mostofsky & Ewen, ; Mous et al, ; Pillai et al, ]. Severe congenital motor deficits—cerebral palsy—are independently associated with epilepsy [Gururaj, Sztriha, Bener, Dawodu, & Eapen, ; Wallace, ], but such severe deficits make up only a small fraction of the high proportion of children with ASD who often have more subtle motor deficits.…”

Deconstructing autism: from unitary syndrome to contributory developmental endophenotypes

“…In a recent contemporaneous analysis of symptom burden of non-ASD-specific neurodevelopmental traits and ASD recurrence in the siblings of affected probands ( Mous, Jiang, Agrawal, & Constantino, 2017 ) it was observed that Attention Deficit Hyperactivity Disorder (ADHD) symptoms and motor coordination impairment jointly accounted for a large share of the variance (over 50%) in both categorical ASD recurrence and quantitative trait severity of recurrent autistic syndromes in families affected by autism. These findings in a clinical family cohort confirmed observations from general population studies ( Lichtenstein, Carlstrom, Rastam, Gillberg, & Anckarsater, 2010 ), indicating substantial genetic overlap between the characterizing symptoms of autism and those of both inattention/hyperactivity and developmental coordination disorder.…”