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

Sinead Morrison,Samuel J R A Chawner,Marianne B M Van Den Bree,Claudia Vingerhoets,Ann Swillen,Therese A M J Van Amelsvoort,Stefanie Linden,Elfi Vergaelen,David E J Linden,Michael J Owen

doi:10.1038/s41398-020-0736-7

Abstract

22q11.2 Deletion Syndrome (22q11.2DS) is associated with high risk of psychiatric disorders and cognitive impairment. It remains unclear to what extent key cognitive skills are associated with psychopathology, and whether cognition is stable over time in 22q11.2DS. 236 children, adolescents and adults with 22q11.2DS and 106 typically developing controls were recruited from three sites across Europe. Measures of IQ, processing speed, sustained attention, spatial working memory and psychiatric assessments were completed. Cognitive performance in individuals was calculated relative to controls in different age groups (children (6–9 years), adolescents (10–17 years), adults (18+ years)). Individuals with 22q11.2DS exhibited cognitive impairment and higher rates of psychiatric disorders compared to typically developing controls. Presence of Autism Spectrum Disorder symptoms was associated with greater deficits in processing speed, sustained attention and working memory in adolescents but not children. Attention deficit hyperactivity disorder in children and adolescents and psychotic disorder in adulthood was associated with sustained attention impairment. Processing speed and working memory were more impaired in children and adults with 22q11.2DS respectively, whereas the deficit in sustained attention was present from childhood and remained static over developmental stages. Psychopathology was associated with cognitive profile of individuals with 22q11.2DS in an age-specific and domain-specific manner. Furthermore, magnitude of cognitive impairment differed by developmental stage in 22q11.2DS and the pattern differed by domain.

Highlights

22q11.2 Deletion Syndrome (22q11.2DS) is associated with high risk of psychiatric disorders and cognitive impairment
In young individuals with 22q11.2DS we investigated whether any links with cognitive performance and the presence of autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) or anxiety disorders differed for children and adolescents
There was no difference between sibling and community controls in Full scale IQ (FSIQ) (p = 0.322), verbal IQ (VIQ) (p = 0.841) or performance IQ (PIQ) (p = 0.318)

Summary

Methods

Participants Three hundred and forty-two participants (236 individuals with 22q11.2DS and 106 controls) were recruited from three sites across Europe (see Supplementary Table 1). Mean FSIQ, VIQ, and PIQ scores were compared between sibling and community controls with t-tests (with correction for unequal variance if applicable) to investigate whether these different groups of typically developing individuals performed differently. Within each developmental stage the mean score for the control sample (typically developing siblings for the children and adolescents and community controls for the adults) was subtracted from the score of each individual with 22q11.2DS for each cognitive measure. This produced a difference score for each individual with 22q11.2DS on each measure. If the original p-value is below the Benjamini-Hochberg critical value, it survives FDR correction

Results

Discussion

Limitations