Habituation to Social Information Is Associated with Repetitive Behavior in 16p11.2 Deletion and Duplication

Background: Recurrent copy number variations (CNVs) at the 16p11.2 locus (Weiss et al., 2008) are associated with autism spectrum disorder (ASD) and ASD symptoms (Hanson et al., 2015), including social difficulties and increased restricted and repetitive behaviors (RRBs). At the neural level, individuals with 16p11.2 CNVs exhibit atypical social information processing such that rapid habituation to social information is evident in 16p11.2 deletion and duplication carriers, opposed to the pattern of rapid nonsocial habituation in typical populations (Hudac et al., 2015). Rapid habituation may indicate lower salience of related stimuli. Lower salience of social information and increased relative response to nonsocial motion in those with 16p11.2 CNVs lead us to hypothesize an increased prevalence of RRBs which may be related to habituation patterns.

Objectives: Determine the extent by which social and nonsocial information habituation is associated with RRBs in individuals with 16p11.2 deletion and duplication.

Methods: Participants (N = 329, see Table 1) completed phase 1 of the Simons Variation in Individuals Project (Simons VIP, https://simonsvipconnect.org/), which included in-person clinical, behavioral, and medication characterization. A subset of individuals with 16p11.2 CNVs (N = 21; the majority with fluent verbal skills) also completed neural characterization via electroencephalography in which habituation was established as changes in neural response over time to social and nonsocial stimuli (i.e., moving hands vs tubes). First, we quantified RRBs in 16p11.2 CNVs as reflected by the ADOS scores including calibrated severity score (CSS; total, social affect, restricted and repetitive behavior) and compared between individuals with 16p11.2 deletion (DEL) and 16p11.2 duplication (DUP). Second, we extended prior analyses by investigating the relationship between RRBs and social habituation using multilevel analyses with Tukey correction for multiple comparisons.

Results: As a group, DEL carriers and DUP carriers did not demonstrate significant differences in CSS scores; however, when considering only those without fluent speech (n = 81), the DEL carriers showed a significantly higher ratio of repetitive behavior relative to their social difficulties compared to DUP carriers, p =.002. Regarding habituation, DUP carriers with more RRBs habituated more rapidly to social motion (i.e., positive slope in Figure 1), r = .71, p = .031, while DEL carriers with more RRBs sensitized to social motion (i.e., negative slope in Figure 1), r = -.59, p = .046. Habituation to nonsocial motion was not related to RRBs in 16p11.2 carriers, p’s > .66.

Conclusions: Distinct social habituation patterns related to RRB severity were found for those with 16p.11.2 deletions and duplications. Sensitization to social motion, as found for the DEL carriers may indicate either an initial delay in processing social information or potentially increasing engagement with social information over time (Hudac et al., 2015; 2017; Jones et al., 2016). Individuals with deletions and without fluent speech language also show increased relative severity of RRBs; habituation studies may help to explain differing rates.