Executive functioning and its relation to autism and ADHD symptomatology in 22q11.2 Deletion Syndrome

Children with 22q11.2 deletion syndrome (22q11DS; velo-cardio-facial-syndrome) are at risk for the developmental disorders attention-deficit-hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). In the present study the relation between executive functioning (EF) and severity of ADHD and ASD symptoms was examined, since EF is known to be important in relation to emotional and behavioral problems. 58 children (38 females) with a mean age of 13.5 (SD 2.6) years participated. Standardized assessment was used to evaluate the presence of ASD and ADHD symptomatology. Major aspects of EF, including cognitive flexibility, inhibition, sustained attention, distractibility, working memory, reaction speed, perseveration, and planning were evaluated. The profile of EF in 22q11DS was characterized by weaker performance, compared to the norm, on all subdomains of EF, except for perseveration. Poor cognitive flexibility and inhibition, and high distractibility were found to be related to more severe ASD symptoms, while poor quality of sustained attention, and high distractibility were related to more severe ADHD symptoms. Children with 22q11DS experience impairments in EF and the degree of impairment on specific EF subdomains is related to severity of ASD or ADHD symptomatology. These results may help in defining the mediating role of neurocognitive dysfunctions in the development of social and behavioral problems in 22q11DS. Background Children with the congenital genetic disorder 22q11.2 deletion syndrome (22q11DS) are at risk for developmental disorders such as attention-deficit-hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) (Antshel et al. 2006; Antshel et al. 2007; Niklasson et al. 2009). Already in childhood and adolescence there is a substantially higher prevalence, compared to typical controls, of different behavioral and emotional problems, such as problems in attention regulation, impulsivity, communication and social interaction, that are part of ADHD and ASD (Antshel et al. 2007; Fine et al. 2005; Vorstman et al. 2006). Because it is widely known that genetic factors are involved in those developmental disorders, investigating a genetic syndrome that is associated with symptoms of these disorders is an unique opportunity to improve our knowledge about the neural basis of these disorders (Rutter 1997; Scourfield 1999). Especially, investigating neuropsychological dysfunctions as possible underlying mechanisms of the behavioral and emotional problems of those disorders in 22q11DS may provide insight in the etiology of ASD and ADHD. Deficits in these executive functions that regulate behavior and thought (Blakemore and Choudhury 2006; Anderson 2001), are found to underlie behavior and adaptation problems observed in ADHD (Barkley 1997; Sonuga-Barke 2003) and ASD (Ozonoff et al.1991; Hill 2004; Gargaro et al. 2011). EF could therefore be important in determining vulnerability to ASD and ADHD symptomatology in individuals with 22q11DS. Insight in this relation may provide opportunities to develop interventions that improve cognitive functioning in children with 22q11DS and may lead to a better developmental outcome. Recently, one preliminary study reported gains in cognition after a cognitive remediation program in adolescents with 22q11DS (Harrell et al. 2013). Across studies in 22q11DS, a broad range of EF has been investigated with different aspects studied in different samples. Dysfunctions have been found in processing speed, cognitive flexibility, mental set-shifting, sustained and selective attention, working memory, inhibition, planning and problem solving (Ousley et al. 2007; Woodin et al. 2001; Rockers et al. 2009; Campbell et al. 2010; Lewandowski et al. 2007; Shashi et al. 2010; Antshel et al. 2008; Niklasson et al. 2005; Furniss et al. 2011; Stoddard et al. 2011; Lajiness-O'Neill et al. 2006; Sobin et al. 2005; Gur et al. 2014). The heterogeneity in methods precludes to determine a clear EF profile and may have contributed to the lack of consistent patterns in findings so far. For example, in some studies response inhibition has been reported to be impaired in 22q11DS (Sobin et al. 2005; Antshel et al. 2008; Campbell et al. 2010), whereas in other studies such impairment was not found (Lajiness-O'Neill et al. 2006; Gothelf et al. 2007).