Neurocognitive development in 22q11.2 deletion syndrome: comparison with youth having developmental delay and medical comorbidities

Abstract

The 22q11.2 deletion syndrome (22q11DS) presents with medical and neuropsychiatric manifestations including neurocognitive deficits. Quantitative neurobehavioral measures linked to brain circuitry can help elucidate genetic mechanisms contributing to deficits. To establish the neurocognitive profile and neurocognitive 'growth charts', we compared cross-sectionally 137 individuals with 22q11DS ages 8-21 to 439 demographically matched non-deleted individuals with developmental delay (DD) and medical comorbidities and 443 typically developing (TD) participants. We administered a computerized neurocognitive battery that measures performance accuracy and speed in executive, episodic memory, complex cognition, social cognition and sensorimotor domains. The accuracy performance profile of 22q11DS showed greater impairment than DD, who were impaired relative to TD. Deficits in 22q11DS were most pronounced for face memory and social cognition, followed by complex cognition. Performance speed was similar for 22q11DS and DD, but 22q11DS individuals were differentially slower in face memory and emotion identification. The growth chart, comparing neurocognitive age based on performance relative to chronological age, indicated that 22q11DS participants lagged behind both groups from the earliest age assessed. The lag ranged from less than 1 year to over 3 years depending on chronological age and neurocognitive domain. The greatest developmental lag across the age range was for social cognition and complex cognition, with the smallest for episodic memory and sensorimotor speed, where lags were similar to DD. The results suggest that 22q11.2 microdeletion confers specific vulnerability that may underlie brain circuitry associated with deficits in several neuropsychiatric disorders, and therefore help identify potential targets and developmental epochs optimal for intervention.

Figure 1

The neurocognitive profile (mean ± SEM Z-scores) for accuracy and speed in Typically Developing (TD, blue line), 22q11.2 Deletion Syndrome (22q11DS, red line) and Developmental Delay with medical comorbidities (DD, orange line). Accuracy scores are presented for Executive (ABF =Abstraction and mental flexibility; ATT = Attention; WM = Working memory), Episodic Memory (VMEM = Verbal Memory, FMEM = Face Memory, SMEM = Spatial Memory), Complex Cognition (LAN = Verbal-Language mediated reasoning, NVR = Nonverbal Reasoning, SPA = Spatial processing), Social Cognition (EMI = Emotion Identification, EMD = Emotion Intensity Differentiation, AGD = Age Differentiation). Speed measures are also available for Praxis (MOT = Motor Speed, SM = Sensorimotor Speed).

Figure 2

Chronological age compared to predicted neurocognitive age in years for Typically Developing participants (TD, blue line), 22q11.2 Deletion Syndrome (22q11DS, red line) and Developmental Delay with medical comorbidities (DD, orange line). Growth charts are provided for a. Predicted age based on all scores (All Domains), b–f. Predicted age based on tests grouped by each of the five domains.