Working Memory Impairments in Chromosome 22q11.2 Deletion Syndrome: The Roles of Anxiety and Stress Physiology

Abstract

Stress and anxiety have a negative impact on working memory systems by competing for executive resources and attention. Broad memory deficits, anxiety, and elevated stress have been reported in individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS). We investigated anxiety and physiological stress reactivity in relation to visuospatial working memory impairments in 20 children with 22q11.2DS and 32 typically developing (TD) children ages 7 to 16. Children with 22q11.2DS demonstrated poorer working memory, reduced post-stress respiratory sinus arrhythmia recovery, and overall increased levels of cortisol in comparison to TD children. Anxiety, but not physiological stress responsivity, mediated the relationship between 22q11.2DS diagnosis and visuospatial working memory impairment. Findings indicate that anxiety exacerbates impaired working memory in children with 22q11.2DS.

Cognitive deficits in childhood, adolescence and adulthood in 22q11.2 deletion syndrome and association with psychopathology

“…The presence of anxiety disorder, however, was not associated with cognitive function in either the current or previous study including some of the same participants 2 , providing further suggestion that these traits may not be linked in 22q11.2DS. Other research which found a relationship between anxiety and working memory impairments 14 controlled for ADHD as a covariate in the analysis, which may explain different findings.…”

“…Other research has suggested that cognition may mediate psychopathology, for example, that deficits in executive functioning may index vulnerability to ASD or ADHD in children with 22q11.2DS 13 . Conversely, reverse causation has been proposed, with the findings that presence of anxiety symptoms may mediate the relationship between 22q11.2DS and working memory capacity, with greater anxiety linked to less efficient cognitive performance 14 . Other research has reported that the presence of ASD or ADHD may predict poorer executive functioning in 22q11.2DS 15 .…”

Lower cortisol levels and attenuated cortisol reactivity to daily-life stressors in adults with 22q11.2 deletion syndrome

“…Jacobson and colleagues (Jacobson et al, 2016) found increased end-of-the-morning cortisol levels (collected around 11:00 h) in a sample of 11 children with 22q11DS compared to HC. Another study investigating cortisol reactivity to a stressful working memory task, did not find significant differences in cortisol reactivity and recovery in relation to the task in 20 children with 22q11DS (Sanders et al, 2017). However, compared to HCs, an overall increase in afternoon salivary cortisol levels in 22q11DS relative to HCs were detected, potentially indicating abnormal HPA-axis functioning in this group.…”

“…The current study therefore aims to examine, for the first time, overall cortisol levels, diurnal slope, and cortisol reactivity to daily life stressors using ESM in adults with 22q11DS. Based on previous findings (Jacobson et al, 2016;Sanders et al, 2017), we hypothesize that in their everyday lives, individuals with 22q11DS, will show 1) higher overall cortisol levels, 2) a flatter diurnal slope, and 3) an blunted cortisol response to activity-related stress, when compared to the comparison subjects (HCs).…”

“…Given the abovementioned relevance of stress reactivity for mental and somatic health, it is rather surprising that little attention has been paid to the HPA axis function in 22q11DS adults. To our knowledge, only two studies (both in children) investigated cortisol and stress reactivity in 22q11DS individuals (Jacobson et al, 2016;Sanders et al, 2017). Jacobson and colleagues (Jacobson et al, 2016) found increased end-of-the-morning cortisol levels (collected around 11:00 h) in a sample of 11 children with 22q11DS compared to HC.…”