Exploring Social Profiles of Individuals with 16p11.2 Deletion and Duplication

Background: Copy number variation (CNV) of the 16p11.2 chromosomal region has been associated with a wide range of neurodevelopmental outcomes. Approximately 19% of pediatric duplication carriers and 26% of pediatric deletion carriers meet criteria for a diagnosis of autism spectrum disorder, and a majority of carriers exhibit some autistic features (Green Snyder et al., 2016; Hanson et al., 2015). Few studies have investigated specific patterns of social strengths and challenges in 16p11.2 CNV carriers. Mouse model studies of 16p11.2 deletion have reported a pattern of intact social approach with atypical social interactions (Yang et al., 2015). Recently, clinical phenotyping of a 16p11.2 duplication cohort has similarly revealed a possible social profile of intact social motivation in the presence of impacted social cognition (Green Snyder et al., 2016). Further investigation of social behaviors in a large cohort of 16p11.2 duplication and deletion carriers may further validate this social profile.

Objectives: To explore social profiles of individuals with 16p11.2 deletions and duplications.

Methods: Participant data from 223 children with 16p11.2 deletions and 100 children with 16p11.2 duplications were extracted from the Simons VIP Phase 2 data (Simons VIP Consortium, 2012). A repeated measures ANOVA was used to test whether mean T-scores differed on theoretically derived subscales of the Social Responsiveness Scale, Second Edition (SRS-2; Constantino & Gruber, 2012) within the 16p11.2 duplication and deletion groups.

Results: For the 16p11.2 duplication group, results showed a significant main effect of SRS-2 subscale on subscale mean T-score, Greenhouse-Geisser Adjusted F(3.25, 321.62) = 28.65, p < 0.001, partial ω² = 0.22. Follow-up paired t-tests among SRS-2 subscales using Dunn-Sidak adjustment revealed that the Social Motivation subscale had a lower mean T-score, suggestive of better developed social motivation abilities, compared to Social Awareness (t(99) = -6.08, adjusted p < 0.001, d = -0.56), Social Cognition (t(99) = -7.21, adjusted p < 0.001, d = -0.73), Social Communication (t(99) = -5.42, adjusted p < 0.001, d = -0.54), and Restrict Interests and Repetitive Behaviors (RRB; t(99) = -8.18, adjusted p < 0.001, d = -0.82) subscales. Similarly, for the 16p11.2 deletion group, results showed a significant main effect of SRS-2 subscale on subscale mean T-score, Greenhouse-Geisser Adjusted F(3.06, 680.29) = 10.66, p < 0.001, partial ω² = 0.04. Follow-up paired t-tests among SRS-2 subscales using Dunn-Sidak adjustment revealed that the Social Motivation subscale had a lower mean T-score compared to Social Cognition (t(222) = -4.14, adjusted p < 0.001, d = -0.28), Social Communication (t(222) = -6.37, adjusted p < 0.001, d = -0.43), and RRB (t(222) = -2.92, adjusted p < 0.05, d = -0.23) subscales.

Conclusions: The social profile of 16p11.2 CNV carriers was quantified in a large sample using standardized caregiver report. Evidence suggests that social motivation represents a relative social strength for both 16p11.2 duplication and deletion carriers. Further investigations should explore social motivation in other standardized measures along with the developmental trajectory of social motivation in individuals with 16p11.2 CNV.