Neurocognitive Functioning in Patients with 22q11.2 Deletion Syndrome: A Meta-Analytic Review

Abstract

The 22q11.2 deletion syndrome (22q11.2DS) is a known risk factor for development of schizophrenia and is characterized by a complex neuropsychological profile. To date, a quantitative meta-analysis examining cognitive functioning in 22q11.2DS has not been conducted. A systematic review of cross-sectional studies comparing neuropsychological performance of individuals with 22q11.2DS with age-matched healthy typically developing and sibling comparison subjects was carried out. Potential moderators were analyzed. Analyses included 43 articles (282 effects) that met inclusion criteria. Very large and heterogeneous effects were seen for global cognition (d = - 1.21) and in specific neuropsychological domains (intellectual functioning, achievement, and executive function; d range = - 0.51 to - 2.43). Moderator analysis revealed a significant role for type of healthy comparison group used (typically developing or siblings), demographics (age, sex) and clinical factors (externalizing behavior). Results revealed significant differences between pediatric and adult samples, with isolated analysis within the pediatric sample yielding large effects in several neuropsychological domains (intellectual functioning, achievement, visual memory; d range = - 0.56 to - 2.50). Large cognitive deficits in intellectual functioning and specific neuropsychological variables in individuals with 22q11.2DS represent a robust finding, but these deficits are influenced by several factors, including type of comparison group utilized, age, sex, and clinical status. These findings highlight the clinical relevance of characterizing cognitive functioning in 22q11.2DS and the importance of considering demographic and clinical moderators in future analyses.

Genes To Mental Health (G2MH): A Framework to Map the Combined Effects of Rare and Common Variants on Dimensions of Cognition and Psychopathology

“…Multimorbid presentation of neurodevelopmental and psychiatric conditions is common (9)(10)(11)(12). All RGDs studied to date affect cognition to varying degrees and affect a broad range of cognitive functions, including reaction time, attention, executive functions, and social cognition (13,14). Early studies highlighted distinctive behavioral profiles, such as social disinhibition, excessive empathy, and non-social anxiety described in 7q11.23 deletions (Williams-Beuren syndrome (15)); insatiable appetite in paternal 15q11.2-q13 deletions (Prader-Willi syndrome (16)); sleep disturbances in 17p11.2 deletions (Smith Magenis syndrome) (17); as well as childhood apraxia of speech in 16p11.2 proximal deletions (18).…”

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

“…However, adding site as a covariate to the analyses generally did not alter results, except there was a significant difference between children and adolescents on working memory which was previously not significant. Furthermore, it is a strength that we have included adults, as there is far less research on older individuals than paediatric 22q11.2DS samples 31 .…”

“…This may introduce bias as our comparisons for child and adolescence groups consisted of family controls. A meta-analysis reported that comparing the cognitive performance of individuals with 22q11.2DS to community controls produced smaller effect sizes than comparing against control siblings 31 . However, this did not appear to be the case in the current study, with effect sizes of a similar magnitude across developmental stages.…”

“…The majority of the studies of specific cognitive domains in 22q11.2DS have focussed on children and adolescents although it is recognised that many cognitive functions continue to mature through early adulthood 27,28 . Our understanding of cognitive function in adults with the deletion thus remains limited [29][30][31] . One study found that adults with 22q11.2DS exhibited deficits in visuoperceptual, planning, abstract, and social cognition compared to age-matched, gender-matched, and IQ-matched controls, which further reinforces the importance of considering specific cognitive domains beyond a sole focus on IQ 32 .…”

“…However, another study with a similar age range investigating working memory abilities found that individuals with 22q11.2DS caught up with controls by age 25 26 . A recent meta-analysis of cognitive functioning in 22q11.2DS compared to controls reported that in paediatric samples there was evidence for greater cognitive impairment in older children, but in adulthood there was an improvement in cognitive abilities over time 31 , highlighting the importance of looking over a wide age range to understand better the continuing development of cognitive functions in 22q11.2DS. Furthermore, it is a general methodological limitation of previous research that different studies with relatively small numbers of participants have used different cognitive testing batteries, limiting comparisons that can be made across samples 31 .…”