Interrelationship Between Cognitive Control, Anxiety, and Restricted and Repetitive Behaviors in Children with 22q11.2 Deletion Syndrome

Abstract

Restricted and repetitive behaviors (RRB) are common in individuals with 22q11.2 microdeletion syndrome (22q11.2DS), yet the underlying mechanisms of these behaviors remain poorly characterized. In the present pilot investigation, we aimed to further our understanding of RRB in 22q11.2DS by exploring their relationship with cognitive control and anxiety as well as with sex, chronological age, and full‐scale IQ. Parents of 38 children with 22q11.2DS (17 females; Mage = 11.15 years, SD = 2.46) completed the Social Communication Questionnaire as a measure of RRB and social and communication (SC) problems and the Behavioral Assessment System for Children‐2 as a measure of anxiety and cognitive control. Higher RRB scores were significantly associated with higher anxiety levels (r = 0.44, P = 0.006), more impairments in cognitive control (r = 0.56, P < 0.001), and higher SC scores (r = 0.43, P = 0.011). In the first step of the hierarchical regression model, anxiety accounted for 24.5% of variance (F = 10.05, P = 0.003); cognitive control accounted for an additional 18.1% of variance (Fchange = 11.15, P < 0.001) in the second step; SC score accounted for only 0.8% of additional variance in the third step (Fchange = 0.40, P = 0.53). The final model explained 43.4% of variance (F = 7.42, P = 0.001), with cognitive control as a unique independent predictor of RRB score (t = 2.52, P = 0.01). The current study provides the first exploration of the cognitive control—anxiety—RRB link in individuals with 22q11.2DS and points to cognitive control as a potentially viable target for treatments aimed at reducing RRB. Autism Res 2019, 12: 1737–1744. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary People with 22q11.2 deletion syndrome show high levels of repetitive behaviors, however, the previous research has not explored why people with this syndrome exhibit high rates of repetitive behaviors. Understanding the reasons for the high levels of repetitive behaviors is important given that these behaviors can be highly impairing. Our study found that repetitive behaviors were associated with impaired ability to self‐regulate and high levels of anxiety. These findings need to be further replicated; however, they are important as they suggest potentially promising ways of reducing these behaviors.

Toward better characterization of restricted and repetitive behaviors in individuals with germline heterozygous PTEN mutations

“…Second, previous research has suggested a strong shared variance between IQ and executive functioning (EF) at both a behavioral and genetic level (Engelhardt et al, 2016; Friedman et al, 2008). Given the well‐established link between IS and EF impairments (South et al, 2005; Uljarević et al, 2019; Uljarević, Arnott, et al, 2017; Uljarević & Evans, 2017; Wallace et al, 2016) and EF deficits with the presence of PTEN mutations (Busch et al, 2013, 2019; Frazier et al, 2015), it is possible that in our study FSIQ also represented a proxy for EF. Indeed, a recent study by our group has found that more impairments in the set‐shifting EF subdomain predicted higher IS severity in individuals with PTEN mutations and individuals with macrocephalic ASD (Uljarević et al, 2021).…”

“…RRB are a core diagnostic symptom domain of ASD and one of the earliest predictors of subsequent ASD diagnosis (Canu et al, 2020; Ozonoff et al, 2008). RRB are also observed across a range of other neurodevelopmental, neuropsychiatric disorders, and genetic syndromes including Down syndrome (Evans et al, 2014; Evans & Gray, 2000; Glenn et al, 2015; Uljarević & Evans, 2017), Fragile X syndrome (Moss et al, 2009; Oakes et al, 2016), 22q11.2 deletion syndrome (Uljarević et al, 2019), Williams syndrome (Rodgers et al, 2012; Vivanti et al, 2019), and Prader‐Willi syndrome (Flores et al, 2011; Greaves et al, 2006). Regardless of the disorder, RRB represents a complex and heterogeneous cluster of symptoms and behaviors ranging from simple motor mannerisms, such as hand or finger flapping or twisting, to complex routines or rituals.…”

Deconstructing the repetitive behaviour phenotype in autism spectrum disorder through a large population‐based analysis

“…The positive significant association identified in this study between Insistence on Sameness with age and FSIQ aligns with the conceptualization of this RRB domain as higher order domain and with findings from both longitudinal and cross-sectional studies (Bishop et al, 2006;Richler et al, 2010). Based on the fact that during normative development, occurrence and rise in Insistence on Sameness tend to be concomitant with the occurrence of normative fears (Evans et al, 1999) it has been suggested that Insistence on Sameness serves as an early form of self-regulation by exerting control, constraining the environment thus limiting unpredictability, and reducing normative fears (Uljarević et al, 2017a;Uljarević & Evans, 2017;Uljarević et al, 2019). Normative fears occur at earlier stages of typical development, and, unlike clinical anxiety, are transitory in nature (Gullone, 2000).…”

“…This is further supported by the relatively recent small scale, pilot Randomised Controlled Trial of a parent group intervention by Grahame and colleagues (2015) which reported that for instance targeting Circumscribed Interests had a positive impact on that particular RRB domain but not on Repetitive Motor Behaviours. Further, as noted, existing evidence suggests that elevated anxiety and impaired cognitive control are related to IS but not Repetitive Motor Behaviours (Lidstone, Uljarević et al, 2014;Uljarević et al, 2017a;Uljarević et al, 2019) indicating that targeting anxiety and impaired selfregulation might be a viable mechanisms for reducing Insistence on Sameness but not Repetitive Motor Behaviours. Since RRB represent dimensional traits that intersect a wide range of neurodevelopmental and neuropsychiatric disorders and extend well into the general population (Evans et al, 2017;Leekam et al, 2011;Uljarević et al, 2017b;Uljarević et al, 2019) it will be important for future studies to explore evidence for the distinctiveness of RRB domains across both typical development and disorders using sensitive and comprehensive RRB measures such as the Repetitive Behaviour Questionnaire-2 (RBQ-2; Barrett et al, 2015) and the Childhood Routines Inventory-Revised (Evans et al, 2017).…”

“…Normative Repetitive Motor Behaviours and Insistence on Sameness are suggested to play adaptive roles during development with Repetitive Motor Behaviours being associated with neuromuscular development (Thelen, 1979;Uljarević et al, 2017c) and Insistence on Sameness, as already noted, acting as a means of limiting unpredictability and reducing ensuing fears (Laing et al, 2009;Leekam et al, 2011;Uljarević et al, 2017a;Uljarević et al, 2019). Although Repetitive Motor Behaviours and Insistence on Sameness are adaptive during early development, if they persist, they may negatively influence subsequent development (Larkin et al, 2017;Leekam et al, 2011).…”