Prospective Longitudinal Studies of Infant Siblings of Children With Autism: Lessons Learned and Future Directions

Objective: The objectives of this review are to highlight the impact of the first decade of high-risk (HR) infant sibling work in autism spectrum disorder (ASD) and to identify potential areas of translational focus for the next decade of research.

Method: A group of clinicians and researchers in ASD working both inside and outside of the HR design met on a regular basis to review the infant sibling research, and came to an agreement on areas that had changed clinical practice and areas that had the potential to change practice with further research. The group then outlined several methodological and translational challenges that must be addressed in the next decade of research if the field is to reach its potential.

Results: The review concluded that the HR design has yielded an understanding that ASD often, but not always, begins to emerge between 6 and 18 months, with early signs affecting social communication. Research using the HR design has also allowed a better understanding of the sibling recurrence risk (between 10% and 20%). Emerging areas of interest include the developmental trajectories of social communications skills in the early years, the expression of a milder phenotype in siblings not affected with ASD, and the possibility that early intervention with infant siblings may improve outcomes for those with ASD. Important challenges for the future include linking screening to intervention, collecting large sample sizes while ensuring cross-site reliability, and building in capacity for replication.

Conclusion: Although there are significant methodological and translational challenges for high-risk infant sibling research, the potential of this design to improve long-term outcomes of all children with ASD is substantial.

Keywords: autism; development; longitudinal; opportunities; sibling.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1 % of the population and close to 20 % of prospectively studied infants with an older sibling with ASD. Although significant progress has been made in characterizing the emergence of behavioral symptoms of ASD, far less is known about the underlying disruptions to early learning. Recent models suggest that core aspects of the causal path to ASD may only be apparent in early infancy. Here, we investigated social attention in 6- and 12-month-old infants who did and did not meet criteria for ASD at 24 months using both cognitive and electrophysiological methods. We hypothesized that a reduction in attention engagement to faces would be associated with later ASD.

Methods: In a prospective longitudinal design, we used measures of both visual attention (habituation) and brain function (event-related potentials to faces and objects) at 6 and 12 months and investigated the relationship to ASD outcome at 24 months.

Results: High-risk infants who met criteria for ASD at 24 months showed shorter epochs of visual attention, faster but less prolonged neural activation to faces, and delayed sensitization responses (increases in looking) to faces at 6 months; these differences were less apparent at 12 months. These findings are consistent with disrupted engagement of sustained attention to social stimuli.

Conclusions: These findings suggest that there may be fundamental early disruptions to attention engagement that may have cascading consequences for later social functioning.

Keywords: ASD; Event-related potential; Habituation; Social attention; Social information processing.

The development of attention toward faces was explored during the first 3 years of life in 54 children aged between 3 and 36 months. In contrast to previous research, attention to faces was assessed using both static images and a dynamic video sequence in the same participants. Separate analyses at each age and exploratory longitudinal analyses indicate a preference for faces during the first year, followed by a decline during the second year. These results suggest that attention to faces does not follow a linear increasing pattern over development, and that social attention patterns are influenced by stimulus characteristics.

Keywords: attention; eye tracking; face preference.

Objective: Two hypotheses, gaze aversion and gaze indifference, are commonly cited to explain a diagnostic hallmark of autism: reduced attention to others’ eyes. The two posit different areas of atypical brain function, different pathogenic models of disability, and different possible treatments. Evidence for and against each hypothesis is mixed but has thus far focused on older children and adults. The authors evaluated both mechanistic hypotheses in two sets of experiments at the time of initial diagnosis.

Method: Eye-tracking data were collected in 86 2-year-olds: 26 with autism, tested at initial diagnosis; 38 matched typically developing children; and 22 matched developmentally delayed children. In two experiments, the authors measured response to direct and implicit cueing to look at the eyes.

Results: When directly cued to look at the eyes, 2-year-olds with autism did not look away faster than did typically developing children; their latency varied neither categorically nor dimensionally by degree of eye cueing. Moreover, direct cueing had a stronger sustained effect on their amount of eye-looking than on that of typically developing children. When presented with implicit social cues for eye-looking, 2-year-olds with autism neither shifted their gaze away nor more subtly averted their gaze to peripheral locations.

Conclusions: The results falsify the gaze aversion hypothesis; instead, at the time of initial diagnosis, diminished eye-looking in autism is consistent with passive insensitivity to the social signals in others’ eyes.

Keywords: Autism; Child Psychiatry; Eye Contact; Gaze Aversion.

Background: Previous work has documented lower vocalization rate and consonant acquisition delays in toddlers with autism spectrum disorder (ASD). We investigated differences in these variables at 12, 18, and 24 months in toddlers at high and low risk for ASD.

Method: Vocalization rate and number of different consonants were obtained from speech samples from a prospective study of infant siblings of children with ASD. Three groups were compared: 18 toddlers at low risk for ASD (low-risk control), 18 high-risk siblings without ASD (HRA-), and 10 high-risk siblings with ASD (HRA+).

Results: All groups’ mean language scores were within the normal range. HRA+ toddlers showed consistently lower vocalization rate; vocalization rate did not predict number of different consonants at 12 months for HRA+. HRA-, not HRA+, toddlers had the smallest number of different consonants and produced significantly fewer different consonants than predicted by their vocalization rate at 12 months. Consonant-acquisition trajectories differed between groups, with HRA- showing the greatest increase from 12 to 18 months.

Conclusion: Lower vocalization rate was not associated with reduced number of different consonants in these toddlers. Between-groups differences in developmental trajectories are discussed in the context of the social feedback loop and differential ability to benefit from adult feedback between groups.