Assessment & Research

Distinct neurocognitive profiles and clinical phenotypes associated with copy number variation at the 22q11.2 locus.

O'Hora et al. (2023) · Autism research : official journal of the International Society for Autism Research 2023
★ The Verdict

Kids with 22q11.2 deletion or duplication think slower and less accurately across the board.

✓ Read this if BCBAs assessing or writing plans for clients with 22q11.2 CNVs.
✗ Skip if Clinicians who only serve typically developing learners.

01Research in Context

01

What this study did

The team gave the Penn Computerized Neurocognitive Battery to three groups.

Group one had 22q11.2 deletion. Group two had 22q11.2 duplication. Group three were typical controls.

They tested memory, speed, and accuracy on ten short tasks.

02

What they found

Both CNV groups scored lower than controls on every task.

They were slower and made more errors.

Deletion carriers traded speed for accuracy. Duplication carriers were just slow overall.

03

How this fits with other research

Cummings et al. (2024) show you can give the same Penn battery on Zoom and still get valid scores.

Schneider et al. (2016) already saw daily multitasking slips in teens with the deletion. The new data prove the problem is system-wide, not just real-life tasks.

Storch et al. (2012) found timed fine-motor gaps but normal untimed drawing. P et al. now reveal the same speed issue hits memory, attention, and reasoning too.

04

Why it matters

If a client carries 22q11.2 deletion or duplication, plan for slow processing in every domain. Give extra wait time, break instructions into tiny steps, and record accuracy separately from speed. Remote Penn testing is valid, so you can assess from home when travel is hard.

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Add a 3-second response window to any verbal directive and chart errors separately from latency.

02At a glance

Intervention
not applicable
Design
quasi experimental
Sample size
126
Population
autism spectrum disorder, neurotypical, other
Finding
negative

03Original abstract

Rare genetic variants that confer large effects on neurodevelopment and behavioral phenotypes can reveal novel gene-brain-behavior relationships relevant to autism. Copy number variation at the 22q11.2 locus offer one compelling example, as both the 22q11.2 deletion (22qDel) and duplication (22qDup) confer increased likelihood of autism spectrum disorders (ASD) and cognitive deficits, but only 22qDel confers increased psychosis risk. Here, we used the Penn Computerized Neurocognitive Battery (Penn-CNB) to characterized neurocognitive profiles of 126 individuals: 55 22qDel carriers (MAge  = 19.2 years, 49.1% male), 30 22qDup carriers (MAge  = 17.3 years, 53.3% male), and 41 typically developing (TD) subjects (MAge  = 17.3 years, 39.0% male). We performed linear mixed models to assess group differences in overall neurocognitive profiles, domain scores, and individual test scores. We found all three groups exhibited distinct overall neurocognitive profiles. 22qDel and 22qDup carriers showed significant accuracy deficits across all domains relative to controls (episodic memory, executive function, complex cognition, social cognition, and sensorimotor speed), with 22qDel carriers exhibiting more severe accuracy deficits, particularly in episodic memory. However, 22qDup carriers generally showed greater slowing than 22qDel carriers. Notably, slower social cognition speed was uniquely associated with increased global psychopathology and poorer psychosocial functioning in 22qDup. Compared to TD, 22q11.2 copy number variants (CNV) carriers failed to show age-associated improvements in multiple cognitive domains. Exploratory analyses revealed 22q11.2 CNV carriers with ASD exhibited differential neurocognitive profiles, based on 22q11.2 copy number. These results suggest that there are distinct neurocognitive profiles associated with either a loss or gain of genomic material at the 22q11.2 locus.

Autism research : official journal of the International Society for Autism Research, 2023 · doi:10.1016/j.bandc.2016.02.002