A Prospective Study of Sub-Threshold Autistic-Like Traits In Unaffected Siblings of Children with Autism Spectrum Disorder

Background: Given that autism spectrum disorder (ASD) is influenced by genetic factors, there has been considerable interest in the examination of autistic-like traits/characteristics sometimes seen in relatives. This milder manifestation of familial liability to ASD has been termed the Broader Autism Phenotype (BAP).  To date, most studies of the BAP have focused on parents; only a few have examined siblings of children with ASD. Furthermore, these studies are based on retrospective data, raising concerns about measurement limitations including recall bias.

Objectives: The current study employs a high-risk design to prospectively investigate the occurrence of sub-threshold autistic-like traits among “unaffected” infant siblings of older children already diagnosed with ASD.

Methods: The study draws on data from a longitudinal study of younger siblings of children with ASD, who are enrolled and assessed prospectively. Beginning at age 6 months, these “high-risk” siblings are followed with comprehensive developmental assessments at regular intervals. The current study examined autistic-like traits among high-risk siblings who were not given a diagnosis at age 3 years (“unaffected sibs”) and a low-risk comparison group (“controls”) with no family history of ASD. Participants included 170 “unaffected sibs” and 90 “controls”, for a total of 260 children. Total scores from the Autism Observation Scale for Infants (AOSI) at age 12 months were used in cluster analysis of the entire sample to identify a distinct sub-group of children with sub-threshold autistic-like traits. Cross-tabulation with chi-square test was used to describe the count of “unaffected sibs” and “controls” in the two clusters. Finally, mean scores from the two clusters were compared on ASD symptoms (indexed by the ADI-R & ADOS), cognitive and adaptive abilities, and social emotional difficulties at 36 months of age.

Results: Two distinct clusters with significantly different scores on the AOSI at 12 months were identified. The two clusters had significantly different counts of “unaffected sibs” and “controls” (χ²₍₁₎=10.8; p<.01). Cluster 1 consisted of 37 children (14.2% of total sample) with a mean AOSI score of 10. Within Cluster 1, 33 children came from the “unaffected sibs” (19.4% of that group) while only 4 came from the “controls” (4.5% of that group). Cluster 2 consisted of 223 children (85.8 % of total sample) with a mean AOSI score of 2. Within Cluster 2, 137 children came from the “unaffected sibs” (80.6% of that group) and 86 came from the “controls” (95.5% of that group). Compared to children in Cluster 2, children from Cluster 1 had significantly higher scores on measures of social-communication impairment (indexed by ADI-R domains) and internalizing problems, and lower scores on measures of cognitive and adaptive abilities at 36 months of age.

Conclusions: Study findings provide support for the existence of the sub-threshold autistic-like traits in a proportion of high-risk siblings who do not meet criteria for ASD at 36 months of age. These data suggest that such autistic-like traits may arise at a very early age but that these children follow a different developmental course than those high–risk sibs who are subsequently diagnosed with ASD.