Familiality of behavioral flexibility and response inhibition deficits in autism spectrum disorder (ASD)

Lauren M Schmitt,Erin Bojanek,Michael E Ragozzino,Edwin H Cook,Matthew W Mosconi,John A Sweeney,Stormi P White

doi:10.1186/s13229-019-0296-y

Abstract

BackgroundDiminished cognitive control, including reduced behavioral flexibility and behavioral response inhibition, has been repeatedly documented in autism spectrum disorder (ASD). We evaluated behavioral flexibility and response inhibition in probands and their parents using a family trio design to determine the extent to which these cognitive control impairments represent familial traits associated with ASD.MethodsWe examined 66 individuals with ASD (probands), 135 unaffected biological parents, and 76 typically developing controls. Participants completed a probabilistic reversal learning task (PRL) and a stop-signal task (SST) to assess behavioral flexibility and response inhibition respectively. Rates of PRL and SST errors were examined across groups, within families, and in relation to clinical and subclinical traits of ASD. Based on prior findings that subclinical broader autism phenotypic (BAP) traits may co-segregate within families and reflect heritable risk factors, we also examined whether cognitive control deficits were more prominent in families in which parents showed BAP features (BAP+).ResultsProbands and parents each showed increased rates of PRL and SST errors relative to controls. Error rates across tasks were not related. SST error rates inter-correlated among probands and their parents. PRL errors were more severe in BAP+ parents and their children relative to BAP− parents and their children. For probands of BAP+ parents, PRL and SST error rates were associated with more severe social-communication abnormalities and repetitive behaviors, respectively.ConclusionReduced behavioral flexibility and response inhibition are present among probands and their unaffected parents, but represent unique familial deficits associated with ASD that track with separate clinical issues. Specifically, behavioral response inhibition impairments are familial in ASD and manifest independently from parental subclinical features. In contrast, behavioral flexibility deficits are selectively present in families with BAP characteristics, suggesting they co-segregate in families with parental subclinical social, communication, and rigid personality traits. Together, these findings provide evidence that behavioral flexibility and response inhibition impairments track differentially with ASD risk mechanisms and related behavioral traits.

Highlights

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by socialcommunication abnormalities and restricted, repetitive behaviors (RRBs)
Proband, parent, and control groups differed on the number of errors during the probabilistic reversal learning task (PRL) reversal phase (Table 3; Fig. 1; Χ2(2) = 7.931, p = .02), on the percentage of STOP trial errors made during the stop-signal task (SST) (Fig. 1; F (2, 245) = 8.19, p < .001, η2p = .06), and on the amount of reaction times (RT) slowing from baseline to SST GO trials (Fig. 1; (F (2, 245) = 13.60, p < .001, η2p = .10)
Reductions in behavioral flexibility were more profound in broader autism phenotype” (BAP)+ parents and their children with autism spectrum disorder (ASD), indicating behavioral flexibility may be selectively affected in a subset of ASD families in which subclinical social, communication, or rigid personality traits are present

Summary

Introduction

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by socialcommunication abnormalities and restricted, repetitive behaviors (RRBs). Even with heritability estimates as high as 0.90 [4], our understanding of underlying pathophysiological processes and their relation to ASD traits remains limited owing, in part, to a lack of definitive biological and neurobehavioral markers of core clinical features [5]. Studies identifying biologically based quantitative traits present in both individuals with ASD and their unaffected family members (i.e., endophenotypes) may help delineate characteristic patterns of intergenerational transmission and build mechanistic bridges between etiological processes and clinically relevant behavioral traits [6, 7]. Recent findings indicate that deficits in behavioral flexibility and response inhibition each uniquely contribute to higher-order RRBs, including insistence on sameness and compulsive behaviors [10], suggesting these cognitive control abilities represent distinct targets for family studies aimed at identifying endophenotypic markers associated with ASD.

Methods

Results

Discussion

Conclusion