Neurocognitive profiles of 22q11.2 and 16p11.2 deletions and duplications

Ruben C. Gur*, Carrie E. Bearden, Sebastien Jacquemont, Ann Swillen, Therese van Amelsvoort, Marianne van den Bree, Jacob Vorstman, Jonathan Sebat, Kosha Ruparel, Robert Sean Gallagher, Emily Mcclellan, Lauren White, Terrence Blaine Crowley, Victoria Giunta, Leila Kushan, Kathleen O'Hora, Jente Verbesselt, Ans Vandensande, Claudia Vingerhoets, Mieke van HaelstJessica Hall, Janet Harwood, Samuel J. R. A. Chawner, Nishi Patel, Katrina Palad, Oanh Hong, James Guevara, Charles Olivier Martin, Khadije Jizi, Anne-Marie Belanger, Stephen W. Scherer, Anne S. Bassett, Donna M. McDonald-McGinn, Raquel E. Gur*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Rare recurrent copy number variants (CNVs) at chromosomal loci 22q11.2 and 16p11.2 are genetic disorders with lifespan risk for neuropsychiatric disorders. Microdeletions and duplications are associated with neurocognitive deficits, yet few studies compared these groups using the same measures to address confounding measurement differences. We report a prospective international collaboration applying the same computerized neurocognitive assessment, the Penn Computerized Neurocognitive Battery (CNB), administered in a multi-site study on rare genomic disorders: 22q11.2 deletions (n = 492); 22q11.2 duplications (n = 106); 16p11.2 deletion (n = 117); and 16p11.2 duplications (n = 46). Domains examined include executive functions, episodic memory, complex cognition, social cognition, and psychomotor speed. Accuracy and speed for each domain were included as dependent measures in a mixed-model repeated measures analysis. Locus (22q11.2, 16p11.2) and Copy number (deletion/duplication) were grouping factors and Measure (accuracy, speed) and neurocognitive domain were repeated measures factors, with Sex and Site as covariates. We also examined correlation with IQ. We found a significant Locus x Copy number x Domain x Measure interaction (p = 0.0004). 22q11.2 deletions were associated with greater performance accuracy deficits than 22q11.2 duplications, while 16p11.2 duplications were associated with greater specific deficits than 16p11.2 deletions. Duplications at both loci were associated with reduced speed compared to deletions. Performance profiles differed among the groups with particularly poor memory performance of the 22q11.2 deletion group while the 16p11.2 duplication group had greatest deficits in complex cognition. Average accuracy on the CNB was moderately correlated with Full Scale IQ. Deletions and duplications of 22q11.2 and 16p11.2 have differential effects on accuracy and speed of neurocognition indicating locus specificity of performance profiles. These profile differences can help inform mechanistic substrates to heterogeneity in presentation and outcome, and can only be established in large-scale international consortia using the same neurocognitive assessment. Future studies could aim to link performance profiles to clinical features and brain function.
Original languageEnglish
Number of pages9
JournalMolecular Psychiatry
DOIs
Publication statusE-pub ahead of print - 1 Jul 2024

Keywords

  • CHILDREN
  • PSYCHOSIS
  • BRAIN
  • PSYCHOPATHOLOGY
  • INDIVIDUALS
  • PERFORMANCE
  • PREDICTORS
  • COGNITION
  • VARIANTS
  • LANGUAGE

Fingerprint

Dive into the research topics of 'Neurocognitive profiles of 22q11.2 and 16p11.2 deletions and duplications'. Together they form a unique fingerprint.

Cite this