Selective Deficits in Mental State Attributions in Individuals with Velocardiofacial Syndrome (22q11.2 Deletion Syndrome)

Background: Velocardiofacial syndrome (VCFS; 22q11.2 deletion syndrome) is a genetic disorder resulting from the deletion of the 11.2 band on one copy of chromosome 22.  Individuals with VCFS have a high prevalence of psychiatric disorders, including Autism Spectrum Disorders (ASD, up to 40-50%), narrowly defined autism (up to 19%), and schizophrenia (25-30%).  VCFS individuals have social deficits, including social withdrawal and poor social competence. However, little is currently known about the relationship of these difficulties to Theory of Mind (ToM) skills.

Objectives: Our goal was to evaluate ToM in children and adolescents with VCFS with and without ASD, relative to typically developing controls, using an Animations Task designed to assess implicit aspects of mentalizing. We hypothesized that ToM scores would be lower in VCFS individuals than in controls, and furthermore, would be lowest in VCFS+ASD individuals, intermediate in VCFS-ASD individuals and highest in controls.

Methods: We administered a video-based task at two separate sites, UCLA and SUNY Upstate Medical University, according to the protocols described in Castelli et al (2000) and Abell et al (2000), respectively.  Video clips displayed two types of interactions: ToM videos depicted interactions that represented complex mental states, and Random videos depicted simple movements around the screen. Participants’ verbal descriptions of the videos were rated for intentionality (ie., mentalizing) and appropriateness. Across the two sites, 63 individuals (31 females) with a molecularly confirmed diagnosis of 22q11.2 deletion (VCFS; 16 (25%) of whom met diagnostic criteria for an ASD), and 43 controls (24 females) participated in the study.  We conducted 2x2x2 Repeated Measures ANOVAs (RMANOVA) on the Intentionality and Appropriateness scores, with main factors Condition, Site and Group.  We then assessed the specific effect of ASD by conducting 2x3 RMANOVAs, separately for each site, and correlated Intentionality and Appropriateness scores with Social Responsiveness Scale (SRS) T-scores, covarying for Site and Age.

Results: RMANOVAs for both Intentionality and Appropriateness revealed a significant Condition X Group interaction: at both sites, individuals with VCFS had lower ToM scores than controls, but the two groups performed similarly for the Random condition. For the ASD analyses, Upstate showed a significant Condition X Group interaction for both Intentionality and Appropriateness, such that both VCFS patients with and without ASD performed significantly worse than controls on the ToM, but not Random, condition. UCLA showed a significant Condition X Group interaction for Intentionality only, whereby VCFS-ASD patients performed significantly worse than controls on the ToM, but not Random, condition.  The Intentionality and Appropriateness scores for ToM (but not Random videos) were significantly correlated with SRS scores.

Conclusions: VCFS patients, regardless of the presence of ASD, showed impairments in mentalizing and ToM abilities, which may underlie real-life problems with social interactions.  Future studies could further explore the developmental trajectory of social cognition deficits in VCFS patients with and without ASD, and any relationship with prodromal symptoms for schizophrenia. A better understanding of the social deficits of VCFS patients with and without ASD is essential for the future design of targeted behavioral interventions.