Quantitative trait variation in ASD probands and toddler sibling outcomes at 24 months

Abstract

Background: Younger siblings of children with autism spectrum disorder (ASD) are at increased likelihood of receiving an ASD diagnosis and exhibiting other developmental concerns. It is unknown how quantitative variation in ASD traits and broader developmental domains in older siblings with ASD (probands) may inform outcomes in their younger siblings. Methods: Participants included 385 pairs of toddler siblings and probands from the Infant Brain Imaging Study. ASD probands (mean age 5.5 years, range 1.7 to 15.5 years) were phenotyped using the Autism Diagnostic Interview-Revised (ADI-R), the Social Communication Questionnaire (SCQ), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Siblings were assessed using the ADI-R, VABS-II, Mullen Scales of Early Learning (MSEL), and Autism Diagnostic Observation Schedule (ADOS) and received a clinical best estimate diagnosis at 24 months using DSM-IV-TR criteria (n = 89 concordant for ASD; n = 296 discordant). We addressed two aims: (1) to determine whether proband characteristics are predictive of recurrence in siblings and (2) to assess associations between proband traits and sibling dimensional outcomes at 24 months. Results: Regarding recurrence risk, proband SCQ scores were found to significantly predict sibling 24-month diagnostic outcome (OR for a 1-point increase in SCQ = 1.06; 95% CI = 1.01, 1.12). Regarding quantitative trait associations, we found no significant correlations in ASD traits among proband-sibling pairs. However, quantitative variation in proband adaptive behavior, communication, and expressive and receptive language was significantly associated with sibling outcomes in the same domains; proband scores explained 9-18% of the variation in cognition and behavior in siblings with ASD. Receptive language was particularly strongly associated in concordant pairs (ICC = 0.50, p < 0.001). Conclusions: Proband ASD symptomology, indexed by the SCQ, is a predictor of familial ASD recurrence risk. While quantitative variation in social communication and restricted and repetitive behavior were not associated among sibling pairs, standardized ratings of proband language and communication explained significant variation in the same domains in the sibling at 24 months, especially among toddlers with an ASD diagnosis. These data suggest that proband characteristics can alert clinicians to areas of developmental concern for young children with familial risk for ASD.

Prenatal air pollution influences neurodevelopment and behavior in autism spectrum disorder by modulating mitochondrial physiology

“…In models which used behavior measures (i.e., SRS, ABC) as dependent variables, the VABS Adaptive Behavioral Composite was used as a covariate since these behavioral measures depend on neurodevelopment. VABS is an important predictor of functional abilities in those with ASD [ 55 , 56 ] and children at high-risk for ASD [ 57 , 58 ] and has been shown to be an important covariate to include when studying ABC and SRS in our previous studies [ 40 , 41 ].…”

Attentive brain states in infants with and without later autism

“…This allowed us to test whether our theory-informed selection of the neural correlates of social attention engagement was consistent with a data-driven approach to identifying the most informative brain responses with respect to later ASD diagnosis and symptomatology 39 . We examined the relation between attentive brain states and both categorical outcome of ASD, and dimensional variation in social adaptive skill, in line with recent evidence that the causative factors underlying diagnosis of ASD may be separable from those underlying dimensional variation in relevant symptom domains 40 .…”

Pregnancy data enable identification of relevant biomarkers and a partial prognosis of autism at birth

“…Neuroimaging in babies at high familial risk of autism have revealed increased brain volume that appears before ASD diagnosis [33][34][35]. The authors obtained a high sensitivity and accuracy of ASD prediction, but the restriction to high-risk sibling hampers and limits the generalizability of the conclusion to first born without siblings with ASD [36].…”