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Translational psychiatry
02 03, 2020;10 (1): 53.

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

Sinead Morrison, Samuel J R A Chawner, Therese A M J van Amelsvoort, Ann Swillen, Claudia Vingerhoets, Elfi Vergaelen, David E J Linden, Stefanie Linden, Michael J Owen, Marianne B M van den Bree
Author Information
  1. Sinead Morrison: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, Wales, UK. ORCID
  2. Samuel J R A Chawner: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, Wales, UK.
  3. Therese A M J van Amelsvoort: Department of Psychiatry and Psychology, Maastricht University, Maastricht, The Netherlands.
  4. Ann Swillen: Department of Human Genetics, Faculty of Medicine, KU Leuven, Leuven, Belgium.
  5. Claudia Vingerhoets: Department of Psychiatry and Psychology, Maastricht University, Maastricht, The Netherlands.
  6. Elfi Vergaelen: Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium. ORCID
  7. David E J Linden: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, Wales, UK.
  8. Stefanie Linden: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, Wales, UK.
  9. Michael J Owen: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, Wales, UK.
  10. Marianne B M van den Bree: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, Wales, UK. vandenbreemb@cardiff.ac.uk.
PMID: 32066691 DOI: 10.1038/s41398-020-0736-7

Abstract

22q11.2 Deletion Syndrome (22q11.2DS) is associated with high risk of psychiatric disorders and cognitive impairment. It remains unclear to what extent key cognitive skills are associated with psychopathology, and whether cognition is stable over time in 22q11.2DS. 236 children, adolescents and adults with 22q11.2DS and 106 typically developing controls were recruited from three sites across Europe. Measures of IQ, processing speed, sustained attention, spatial working memory and psychiatric assessments were completed. Cognitive performance in individuals was calculated relative to controls in different age groups (children (6-9 years), adolescents (10-17 years), adults (18+ years)). Individuals with 22q11.2DS exhibited cognitive impairment and higher rates of psychiatric disorders compared to typically developing controls. Presence of Autism Spectrum Disorder symptoms was associated with greater deficits in processing speed, sustained attention and working memory in adolescents but not children. Attention deficit hyperactivity disorder in children and adolescents and psychotic disorder in adulthood was associated with sustained attention impairment. Processing speed and working memory were more impaired in children and adults with 22q11.2DS respectively, whereas the deficit in sustained attention was present from childhood and remained static over developmental stages. Psychopathology was associated with cognitive profile of individuals with 22q11.2DS in an age-specific and domain-specific manner. Furthermore, magnitude of cognitive impairment differed by developmental stage in 22q11.2DS and the pattern differed by domain.

References

  1. Baker, K. & Vorstman, J. A. Is there a core neuropsychiatric phenotype in 22q11.2 deletion syndrome? Curr. Opin. Neurol. 25, 131–137 (2012). [PMID: 22395003]
  2. Niarchou, M. et al. Psychopathology and cognition in children with 22q11.2 deletion syndrome. Br. J. Psychiatry 204, 46–54 (2014). [PMID: 24115343]
  3. Schneider et al. Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome. Am. J. Psychiatry 171, 627–639 (2014). [PMID: 4285461]
  4. Monks, S. et al. Further evidence for high rates of schizophrenia in 22q11.2 deletion syndrome. Schizophr. Res. 153, 231–236 (2014). [PMID: 24534796]
  5. Hoeffding, L. K. et al. Risk of psychiatric disorders among individuals with the 22q11.2 deletion or duplication: a Danish Nationwide, Register-Based Study. JAMA Psychiatry 74, 282–290 (2017). [PMID: 28114601]
  6. Gothelf, D. et al. Risk factors and the evolution of psychosis in 22q11.2 deletion syndrome: a longitudinal 2-site study. J. Am. Acad. Child Adolesc. Psychiatry 52, 1192–203.e3 (2013). [PMID: 24157393]
  7. Antshel, K. M. et al. Cognitive and psychiatric predictors to psychosis in velocardiofacial syndrome: a 3-year follow-up study. J. Am. Acad. Child Adolesc. Psychiatry 49, 333–344 (2010). [PMID: 20410726]
  8. Chawner SJRA et al. The emergence of psychotic experiences in the early adolescence of 22q11.2 Deletion Syndrome. J. Psychiatr. Res. 109, 10–17 (2019). [PMID: 30458299]
  9. Hooper, S. R. et al. A longitudinal examination of the psychoeducational, neurocognitive, and psychiatric functioning in children with 22q11.2 deletion syndrome. Res. Dev. Disabil. 34, 1758–1769 (2013). [PMID: 23506790]
  10. Campbell, L. E. et al. Executive functions and memory abilities in children with 22q11.2 deletion syndrome. Aust. N. Z. J. Psychiatry 44, 364–371 (2010). [PMID: 20307169]
  11. Gur, R. E. et al. Neurocognitive development in 22q11.2 deletion syndrome: comparison with youth having developmental delay and medical comorbidities. Mol. Psychiatry 19, 1205–1211 (2014). [PMID: 24445907]
  12. Green, T. et al. Psychiatric disorders and intellectual functioning throughout development in velocardiofacial (22q11.2 deletion) syndrome. J. Am. Acad. Child Adolesc. Psychiatry 48, 1060–1068 (2009). [PMID: 19797984]
  13. de Sonneville, L. M. J. et al. Executive functioning and its relation to ASD and ADHD symptomatology in 22q11.2 deletion syndrome. Child Neuropsychol. 24, 1–19 (2018). [PMID: 27608887]
  14. Sanders, A. F., Hobbs, D. A., Stephenson, D. D., Jr, Laird, R. D. & Beaton, E. A. O. Working memory impairments in chromosome 22q11.2 deletion syndrome: the roles of anxiety and stress physiology. J Autism Dev Disord. 47, 1573–3432 (2017).
  15. Niklasson, L. & Gillberg, C. The neuropsychology of 22q11 deletion syndrome. A neuropsychiatric study of 100 individuals. Res. Dev. Disabil. 31, 185–194 (2010). [PMID: 19815377]
  16. van Amelsvoort, T. et al. Cognitive deficits associated with schizophrenia in velo-cardio-facial syndrome. Schizophr. Res. 70, 223–232 (2004). [PMID: 15329299]
  17. Weinberger, R. et al. Neurocognitive profile in psychotic versus nonpsychotic individuals with 22q11.2 deletion syndrome. Eur. Neuropsychopharmacol. 26, 1610–1618 (2016). [PMID: 27524298]
  18. Fiksinski, A. M. et al. Neurocognition and adaptive functioning in a genetic high risk model of schizophrenia. Psychol. Med. 49, 1–8 (2018).
  19. Gold, J. M. et al. Selective attention, working memory, and executive function as potential independent sources of cognitive dysfunction in schizophrenia. Schizophr. Bull. 44, 1227–1234 (2017). [>PMCID: ]
  20. Vorstman, J. A. S. et al. A cognitive decline precedes the onset of psychosis in patients with the 22q11.2 deletion syndrome. JAMA Psychiatry 72, 377–385 (2015). [PMID: 25715178]
  21. Chow, E. W. C., Watson, M., Young, D. A. & Bassett, A. S. Neurocognitive profile in 22q11 deletion syndrome and schizophrenia. Schizophr. Res. 87, 270–278 (2006). [PMID: 16753283]
  22. Niarchou, M. et al. Attention deficit hyperactivity disorder symptoms and Psychosis in 22q11.2 deletion syndrome. Schizophr. Bull. 44, 824–833 (2018). [PMID: 29040797]
  23. Duijff, S. N. et al. Cognitive and behavioral trajectories in 22q11DS from childhood into adolescence: a prospective 6-year follow-up study. Res Dev. Disabil. 34, 2937–2945 (2013). [PMID: 23816629]
  24. Chawner, S. J. R. A. et al. Childhood cognitive development in 22q11.2 deletion syndrome: case–control study. Br. J. Psychiatry 211, 223–230 (2017). [PMID: 28882829]
  25. Van Den Heuvel, E. et al. Exploratory study on cognitive abilities and social responsiveness in children with 22q11.2 deletion syndrome (22q11DS) and children with idiopathic intellectual disability (IID). Res. Dev. Disabil. 81, 89–102 (2018).
  26. Antshel, K. M., Fremont, W., Ramanathan, S. & Kates, W. R. Predicting cognition and psychosis in young adults with 22q11.2 deletion syndrome. Schizophr. Bull. 43, 833–842 (2017). [PMID: 27798222]
  27. Foulkes, L. & Blakemore, S.-J. Studying individual differences in human adolescent brain development. Nat. Neurosci. 21, 315–323 (2018). [PMID: 29403031]
  28. Maeder, J. et al. Developmental trajectories of executive functions in 22q11.2 deletion syndrome. J. Neurodev. Disord. 8, 1–12 (2016).
  29. Swillen, A. The importance of understanding cognitive trajectories: the case of 22q11.2 deletion syndrome 29, 1473–6578 (2016).
  30. Jonas, R. K., Montojo, C. A. & Bearden, C. E. The 22q11.2 deletion syndrome as a window into complex neuropsychiatric disorders over the lifespan. Biol. Psychiatry 75, 351–360 (2014). [PMID: 23992925]
  31. Moberg, P. J. et al. Neurocognitive functioning in patients with 22q11.2 deletion syndrome: a meta-analytic review. Behav. Genet. 48, 259–270 (2018). [PMID: 29922984]
  32. Henry, J. C. et al. An investigation of the neuropsychological profile in adults with velo-cardio-facial syndrome (VCFS). Neuropsychologia 40, 471–478 (2002). [PMID: 11749977]
  33. WHO. Global Accelerated Action for the Health of Adolescents (AA-HA!) Guidance to Support Country Implementation (World Health Organization 2017) http://apps.who.int/iris/bitstream/handle/10665/255415/9789241512343-eng.pdf?sequence=1 .
  34. CANTAB. CANTAB Eclipse Version 3 (Cambridge Cognition, Cambridge, 2006).
  35. Chamberlain, S. R. et al. Translational approaches to frontostriatal dysfunction in attention-deficit/hyperactivity disorder using a computerized neuropsychological battery. Biol. Psychiatry 69, 1192–1203 (2011). [PMID: 21047621]
  36. Steele, S., Minshew, N., Luna, B. & Sweeney, J. Spatial working memory deficits in autism. J. Autism Dev. Disord. 37, 605–612 (2007). [PMID: 16909311]
  37. Barnett, J. H. et al. Assessing cognitive function in clinical trials of schizophrenia. Neurosci. Biobehav. Rev. 34, 1161–1177 (2010). [PMID: 20105440]
  38. Gur, R. E. et al. A neurogenetic model for the study of schizophrenia spectrum disorders: the International 22q11.2 Deletion Syndrome Brain Behavior Consortium. Mol. Psychiatry 22, 1664–1672 (2017). [PMID: 28761081]
  39. Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B 57, 289–300 (1995).
  40. Crawford, K. et al. Medical consequences of pathogenic CNVs in adults: analysis of the UK Biobank. J. Med. Genet. 56, 131–138 (2018).
  41. Sigman, M. & McGovern, C. W. Improvement in cognitive and language skills from preschool to adolescence in autism. J. Autism Dev. Disorders 35, 15–23 (2005).
  42. Eliez, S. Autism in children with 22q11.2 deletion syndrome. J. Am. Acad. Child Adoles. Psychiatry 4, 433–434 (2007).
  43. Fiksinski, A. M. et al. Autism spectrum and psychosis risk in the 22q11.2 deletion syndrome. Findings from a prospective longitudinal study. Schizophr. Res. 188, 59–62 (2017).
  44. Lord, C., Rutter, M. & Le Couteur, A. Autism diagnostic interview-revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J. Autism Dev. Disord. 24, 659–685 (1994). [PMID: 7814313]
  45. Berument, S. K., Rutter, M., Lord, C., Pickles, A. & Bailey, A. Autism screening questionnaire: diagnostic validity. Br. J. Psychiatry 175, 444–451 (1999). [PMID: 10789276]
  46. Charman, T. et al. Efficacy of three screening instruments in the identification of autistic-spectrum disorders. Br. J. Psychiatry 191, 554–559 (2007). [PMID: 18055961]
  47. Vorstman, J. A., Breetvelt, E. J., Thode, K. I., Chow, E. W. & Bassett, A. S. Expression of autism spectrum and schizophrenia in patients with a 22q11.2 deletion. Schizophr. Res. 143, 55–59 (2013). [PMID: 23153825]
  48. Niarchou, M., Martin, J., Thapar, A., Owen, M. J. & van den Bree, M. B. The clinical presentation of attention deficit-hyperactivity disorder (ADHD) in children with 22q11.2 deletion syndrome. Am. J. Med. Genet. Part B 168, 730–738 (2015). [PMID: 26400629]
  49. Mariano, M. A., Tang, K., Kurtz, M. & Kates, W. R. Cognitive remediation for adolescents with 22q11 deletion syndrome (22q11DS): a preliminary study examining effectiveness, feasibility, and fidelity of a hybrid strategy, remote and computer-based intervention. Schizophr. Res. 166, 283–289 (2015). [PMID: 26044111]
  50. Smelror, R. E. et al. Healthy adolescent performance with standardized scoring tables for the MATRICS consensus cognitive battery: a multisite study. Schizophr. Bull. 45, 773–783 (2018). [>PMCID: ]
  51. Kates, W. R. et al. Trajectories of psychiatric diagnoses and medication usage in youth with 22q11.2 deletion syndrome: a 9-year longitudinal study. Psychol. Med. 49, 1–9 (2018).
  52. Tang, S. X. et al. Emergent, remitted and persistent psychosis-spectrum symptoms in 22q11.2 deletion syndrome. Transl. Psychiatry 7, e1180 (2017). [PMID: 28742080]
  53. Yi, J. et al. Impact of psychiatric comorbidity and cognitive deficit on function in 22q11.2 deletion syndrome. J. Clin. Psychiatry 76, e1262–e70. (2015). [PMID: 26528648]
  54. D’Angelo, D. et al. Defining the effect of the 16p11.2 duplication on cognition, behavior, and medical comorbidities. JAMA Psychiatry 73, 20–30 (2016). [PMID: 26629640]

Grants

  1. MRF_MRF-154-0001-RG-SKUSE/MRF
  2. MR/L011166/1/Medical Research Council
  3. 507556/Health and Care Research Wales (Ymchwil Iechyd a Gofal Cymru)
  4. MR/L010305/1/RCUK | Medical Research Council (MRC)
  5. MR/T033045/1/Medical Research Council
  6. U01 MH101724/NIMH NIH HHS
  7. MR/N022572/1/Medical Research Council
  8. /Wellcome Trust

MeSH Term

Adolescent
Adult
Autism Spectrum Disorder
Child
Cognition
Cognitive Dysfunction
DiGeorge Syndrome
Europe
Humans
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 7

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