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

Molecular Psychiatry volume 19, pages 1205–1211 (2014)Cite this article

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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.

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Acknowledgements

This study was supported by NIH grants MH087626, MH087636, MH089983 and MH089924. Additional support came from T32 MH019112 (JJY), the Doris Duke Charitable Foundation Clinical Research Fellowship (SXT) and K08 MH 079364 (MEC). We are grateful to the research participants and their parents. We thank Emily Wilkins, Catherine Conroy, Omar Abbas, Amy Cassidy, Allison Mott and Kosha Ruparel of the Neuropsychiatry Section at the University of Pennsylvania for data acquisition and coordination. We also thank Alice Bailey and Jhonna Corson of the ‘22q and You’ Center for clinical coordination of 22q11DS participants and Colleen Franconi and Meghan McNamara of the Human Genetics Division at the Children’s Hospital of Philadelphia for the genetic laboratory assessments of the 22q11DS participants. We also thank Dr Hakon Hakonarson and the Center for Applied Genomics at the Children’s Hospital of Philadelphia for their collaboration in establishing the Philadelphia Neurodevelopmental Cohort.

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Authors and Affiliations

  1. Department of Psychiatry, Neuropsychiatry Section, Prelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    R E Gur, J J Yi, S X Tang, M E Calkins, D Whinna, A Savitt, P J Moberg & R C Gur

  2. Department of Child and Adolescent Psychiatry, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    J J Yi

  3. Division of Human Genetics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    D M McDonald-McGinn, M C Souders, E H Zackai & B S Emanuel

  4. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    D M McDonald-McGinn, E H Zackai & B S Emanuel

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  1. R E Gur
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Gur, R., Yi, J., McDonald-McGinn, D. et al. Neurocognitive development in 22q11.2 deletion syndrome: comparison with youth having developmental delay and medical comorbidities. Mol Psychiatry 19, 1205–1211 (2014). https://doi.org/10.1038/mp.2013.189

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