Deficits in mental state attributions in individuals with 22q11.2 deletion syndrome (velo-cardio-facial syndrome)

Abstract

Velo-cardio-facial syndrome (VCFS; 22q11.2 deletion syndrome) results from a genetic mutation that increases risk for Autism Spectrum Disorder (ASD). We compared Theory of Mind (ToM) skills in 63 individuals with VCFS (25% with an ASD diagnosis) and 43 typically developing controls, and investigated the relationship of ToM to reciprocal social behavior. We administered a video-based task to assess mentalizing at two sites University of California, Los Angeles (UCLA) and State University of New York (SUNY) Upstate Medical University. The videos depicted interactions representing complex mental states (ToM condition), or simple movements (Random condition). Verbal descriptions of the videos were rated for Intentionality (i.e. mentalizing) and Appropriateness. Using Repeated Measures analysis of variance (ANOVA), we assessed the effects of VCFS and ASD on Intentionality and Appropriateness, and the relationship of mentalizing to Social Responsiveness Scale (SRS) scores. Results indicated that individuals with VCFS overall had lower Intentionality and Appropriateness scores than controls for ToM but not for Random scenes. In the SUNY sample, individuals with VCFS, both with and without ASD, performed more poorly than controls on the ToM condition; however, in the UCLA sample, only individuals with VCFS without ASD performed significantly worse than controls on the ToM condition. Controlling for site and age, performance on the ToM condition was significantly correlated with SRS scores. Individuals with VCFS, regardless of an ASD diagnosis, showed impairments in the spontaneous attribution of mental states to abstract visual stimuli, which may underlie real-life problems with social interactions. A better understanding of the social deficits in VCFS is essential for the development of targeted behavioral interventions.

Figure 1

ADI-R and ADOS score profiles for VCFS patients at UCLA and SUNY. Blue represents UCLA and red represents SUNY. ADI-R Module A= Qualitative Abnormalities in Reciprocal Social Interaction; ADI-R Module B = Qualitative Abnormalities in Communication; ADI-R Module C = Restricted, Repetitive, and Stereotyped Patterns of Behavior. Dotted lines represent thresholds for autism criteria in each of the domains. For the ADI-R: Social Interaction = 10; Communication = 8; Stereotypes = 3. For the ADOS: ASD = 7; Autism = 9.

Figure 2

(A): Intentionality scores on ToM and Random conditions, for UCLA and SUNY. Black represents individuals with VCFS and light grey represents controls. Across groups, performance in the ToM condition was significantly better at SUNY in comparison to UCLA. At both sites, in comparison to individuals with VCFS, controls had significantly higher performance in the ToM condition, but did not differ on the Random Condition. Significance levels are indicated as follows: *** p_FDR<0.001; ** p_FDR<0.01; * p_FDR<0.05. Raw scores, rather than age adjusted scores, are presented for visualization purposes. (B) Appropriateness scores on ToM and Random conditions, for UCLA and SUNY. A similar pattern of results was observed for both the Appropriateness and Intentionality ratings (Figure 2A).

Figure 3

(A) Intentionality and (B) Appropriateness for UCLA (left panel) and SUNY (right panel). The shading represents the groups as follows: VCFS+ASD=black; VCFS−ASD=dark grey; controls=light grey. Significance levels are marked as follows: *** p_FDR<0.001; ** p_FDR<0.01; * p_FDR<0.05.

Figure 4

Relationship between Age and ToM Appropriateness for UCLA. Note that there is a significant correlation between age and ToM appropriateness scores for the controls but NOT for the individuals with VCFS.