An Examination of the Relationship of Anxiety and Intelligence to Adaptive Functioning in Children with Chromosome 22q11.2 Deletion Syndrome

Abstract

Objective This study investigates the relationship between anxiety symptoms and adaptive function in children with Chromosome 22q11.2 Deletion Syndrome (22q11.2DS). Methods Seventy-eight children ages 7-14 years with 22q11.2DS and 36 typically developing (TD) children without known genetic syndromes participated in a larger study of neurocognition. Parents completed questionnaires about their child’s anxiety symptoms (Behavior Assessment System for Children, 2nd ed.: BASC-2 and Spence Children’s Anxiety Scale: SCAS) and adaptive functioning (BASC-2 and Adaptive Behavior Assessment System, 2nd ed.: ABAS-II). Within the 22q11.2DS group, different DSM-IV anxiety domains were also analyzed using SCAS subscales. Results Based on parent report, 19% of children with 22q11.2DS had a prior diagnosis of an anxiety disorder vs. 58% with at least one elevated anxiety score (BASC-2 and/or SCAS). Mean BASC-2 anxiety scores were significantly higher in 22q11.2DS (55.6+12.5) than TD (48.3+10; p=0.003) and a greater percentage of children with 22q11.DS (37%) had elevated BASC-2 anxiety scores compared with TD (14%; p=0.01). Higher anxiety scores were related to lower adaptive function (r=−0.27, p=0.015) but there was no relationship between WISC-IV FSIQ and BASC-2 adaptive skills (r=−0.06, p=0.6) in the 22q11.2DS group. For the individual SCAS anxiety subscales, panic-agoraphobia (r=−0.38, p=0.03), physical injury (r=−0.34, p=0.05), and obsessive compulsive disorder (r=−0.47, p=0.005) were significantly negatively related to adaptive function in 22q11.2DS. Conclusions Despite known risk, anxiety is under-identified in children with 22q11.2DS. The presence of anxiety symptoms, but not intelligence levels, in children with 22q11.2DS is negatively correlated with adaptive function and impacts everyday living skills.

The hippocampi of children with chromosome 22q11.2 deletion syndrome have localized anterior alterations that predict severity of anxiety

“…Our results suggest that children with 22q11.2DS who have small hippocampi are more likely to have altered morphology of the anterior hippocampus. This particular variation in hippocampal shape predicted fear of physical injury anxiety score, which is 1 of the 2 strongest anxiety subtypes found in individuals with 22q11.2DS 37 and is related to the anxiety disorders that appear to increase psychosis-proneness. 4,34,36 Therefore, anterior hippocampus morphology may potentially serve as a sensitive neuroanatomical marker for conditions associated with greater schizophrenia risk.…”

“…37 The peak deformation of this basis vector was adjacent to the left vector V.1 in the inferomedial and superolateral aspects of the anterior hippocampus. The areal spread of this basis vector extended posteriorly into the body of the hippocampus.…”

“…Fear of physical injury was the highest subscale score in this sample and in a previous report. 37 Since vector V.1 coefficients were associated with hippocampal volume, we tested multipredictor models for fear of physical injury score that included both hippocampal volume and vector V.1 with age and sex. In these models, only the left vector V.1 (p = 0.029) and age (p = 0.005) retained significant negative effects on the fear of physical injury score after multiple comparison correction.…”

“…Several recent longitudinal studies have shown that, aside from declines in verbal IQ and attention disorders, 6,34,35 one of the strongest predictors of future psychosis in individuals with 22q11.2DS is the presence of a pre-existing anxiety disorder in childhood. 34,36 Importantly, Angkustsiri and colleagues 37 have demonstrated that greater anxiety, but not lower IQ, levels strongly predicted lower adaptive function in children with 22q11.2DS. Of interest is whether the hippocampus may be a component of the neural circuitry contributing to anxiety and the associated risk of schizophrenia.…”

The psychosocial impact of 22q11 deletion syndrome on patients and families: A systematic review

“…Yet, patient psychosocial perspectives were limited; limited findings highlighted patients’ desires to obtain independence, challenges to achieving individualism, and transitioning into adulthood. Reasons for this may include limitations in patients’ social functioning disproportionate to their capabilities in other aspects of daily living (Angkustsiri et al, 2012; Bassett et al, 2011; Butcher et al, 2012; Ho et al, 2012), difficulty maintaining social relationships (Abery & Fahnestock, 1994; May & Simpson, 2003), and having small social circles (Amando, 1993; Knox & Hickson, 2001). However, these patterns were not necessarily found for all 22q11DS patients included in this review: a number of female patients in (Phillips et al, 2017) express strong desires to marry and become good parents.…”