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Fiksinski AM, Bearden CE, Bassett AS, et al. A normative chart for cognitive development in a genetically selected population. Neuropsychopharmacology. 2021;doi: 10.1038/s41386-021-00988-6.
Fiksinski, A. M., Bearden, C. E., Bassett, A. S., Kahn, R. S., Zinkstok, J. R., Hooper, S. R., Tempelaar, W., Vorstman, J. A. S., & Breetvelt, E. J. (2021). A normative chart for cognitive development in a genetically selected population. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, . https://doi.org/10.1038/s41386-021-00988-6
Fiksinski, Ania M, et al. "A normative chart for cognitive development in a genetically selected population." Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology vol. (2021). doi: https://doi.org/10.1038/s41386-021-00988-6
Fiksinski AM, Bearden CE, Bassett AS, Kahn RS, Zinkstok JR, Hooper SR, Tempelaar W, Vorstman JAS, Breetvelt EJ. A normative chart for cognitive development in a genetically selected population. Neuropsychopharmacology. 2021 Mar 29; doi: 10.1038/s41386-021-00988-6. Epub 2021 Mar 29. PMID: 33782512.
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Neuropsychopharmacology. 2021 Mar 29; doi: 10.1038/s41386-021-00988-6. Epub 2021 Mar 29.

A normative chart for cognitive development in a genetically selected population.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Ania M Fiksinski, Carrie E Bearden, Anne S Bassett, Rene S Kahn, Janneke R Zinkstok, Stephen R Hooper, Wanda Tempelaar, Jacob A S Vorstman, Elemi J Breetvelt

Affiliations

  1. Wilhelmina Children's Hospital & University Medical Center Utrecht, Brain Center, Utrecht, The Netherlands. [email protected].
  2. Centre for Addiction and Mental Health, Toronto, ON, Canada. [email protected].
  3. The Dalglish Family 22q Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, ON, Canada. [email protected].
  4. Department of Psychiatry and Neuropsychology, Division of Mental Health, MHeNS, Maastricht University, Maastricht, The Netherlands. [email protected].
  5. Departments of Psychiatry and Biobehavioral Sciences and Psychology, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, USA.
  6. Centre for Addiction and Mental Health, Toronto, ON, Canada.
  7. The Dalglish Family 22q Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
  8. Toronto General Research Institute and Campbell Family Mental Health Research Institute, Toronto, ON, Canada.
  9. Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
  10. Wilhelmina Children's Hospital & University Medical Center Utrecht, Brain Center, Utrecht, The Netherlands.
  11. Department of Psychiatry and Behavioral Health System, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  12. Department of Allied Health Sciences, School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
  13. Program in Genetics and Genome Biology, Research Institute, and Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada.

PMID: 33782512 DOI: 10.1038/s41386-021-00988-6

Abstract

Certain pathogenic genetic variants impact neurodevelopment and cause deviations from typical cognitive trajectories. Understanding variant-specific cognitive trajectories is clinically important for informed monitoring and identifying patients at risk for comorbid conditions. Here, we demonstrate a variant-specific normative chart for cognitive development for individuals with 22q11.2 deletion syndrome (22q11DS). We used IQ data from 1365 individuals with 22q11DS to construct variant-specific normative charts for cognitive development (Full Scale, Verbal, and Performance IQ). This allowed us to calculate Z-scores for each IQ datapoint. Then, we calculated the change between first and last available IQ assessments (delta Z-IQ-scores) for each individual with longitudinal IQ data (n = 708). We subsequently investigated whether using the variant-specific IQ-Z-scores would decrease required sample size to detect an effect with schizophrenia risk, as compared to standard IQ-scores. The mean Z-IQ-scores for FSIQ, VIQ, and PIQ were close to 0, indicating that participants had IQ-scores as predicted by the normative chart. The mean delta-Z-IQ-scores were equally close to 0, demonstrating a good fit of the normative chart and indicating that, as a group, individuals with 22q11DS show a decline in IQ-scores as they grow into adulthood. Using variant-specific IQ-Z-scores resulted in 30% decrease of required sample size, as compared to the standard IQ-based approach, to detect the association between IQ-decline and schizophrenia (p < 0.01). Our findings suggest that using variant-specific normative IQ data significantly reduces required sample size in a research context, and may facilitate a more clinically informative interpretation of IQ data. This approach allows identification of individuals that deviate from their expected, variant-specific, trajectory. This group may be at increased risk for comorbid conditions, such as schizophrenia in the case of 22q11DS.

References

  1. Steele A, Scerif G, Cornish K, Karmiloff-Smith A. Learning to read in Williams syndrome and Down syndrome: syndrome-specific precursors and developmental trajectories. J Child Psychol Psychiatry. 2013;54:754–62. - PubMed
  2. Bernier R, Hudac CM, Chen Q, Zeng C, Wallace AS, Gerdts J, et al. Developmental trajectories for young children with 16p11.2 copy number variation. Am J Med Genet B Neuropsychiatr Genet. 2017;174:367–80. - PubMed
  3. Hall SS, Burns DD, Lightbody AA, Reiss AL. Longitudinal changes in intellectual development in children with Fragile X syndrome. J Abnorm Child Psychol. 2008;36:927–39. - PubMed
  4. Franic S, Dolan CV, van Beijsterveldt CE, Hulshoff Pol HE, Bartels M, Boomsma DI. Genetic and environmental stability of intelligence in childhood and adolescence. Twin Res Hum Genet. 2014;17:151–63. - PubMed
  5. Smeets EE, Townend GS, Curfs LMG. Rett syndrome and developmental regression. Neurosci Biobehav Rev. 2019;104:100–01. - PubMed
  6. Einspieler C, Marschik PB. Regression in Rett syndrome: developmental pathways to its onset. Neurosci Biobehav Rev. 2019;98:320–32. - PubMed
  7. Ballard C, Mobley W, Hardy J, Williams G, Corbett A. Dementia in Down’s syndrome. Lancet Neurol. 2016;15:622–36. - PubMed
  8. Startin CM, D’Souza H, Ball G, Hamburg S, Hithersay R, Hughes KMO, et al. Health comorbidities and cognitive abilities across the lifespan in Down syndrome. J Neurodev Disord. 2020;12:4. - PubMed
  9. Grieco J, Pulsifer M, Seligsohn K, Skotko B, Schwartz A. Down syndrome: Cognitive and behavioral functioning across the lifespan. Am J Med Genet C Semin Med Genet. 2015;169:135–49. - PubMed
  10. Patterson T, Rapsey CM, Glue P. Systematic review of cognitive development across childhood in Down syndrome: implications for treatment interventions. J Intellect Disabil Res. 2013;57:306–18. - PubMed
  11. Davies G, Tenesa A, Payton A, Yang J, Harris SE, Liewald D, et al. Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Mol Psychiatry. 2011;16:996–1005. - PubMed
  12. Batty GD, Deary IJ, Gottfredson LS. Premorbid (early life) IQ and later mortality risk: systematic review. Ann Epidemiol. 2007;17:278–88. - PubMed
  13. Kahn RS, Keefe RS. Schizophrenia is a cognitive illness: time for a change in focus. JAMA Psychiatry. 2013;70:1107–12. - PubMed
  14. Zemel BS, Pipan M, Stallings VA, Hall W, Schadt K, Freedman DS, et al. Growth charts for children with Down syndrome in the United States. Pediatrics. 2015;136:e1204–11. - PubMed
  15. Mircher C, Briceno LG, Toulas J, Conte M, Tanguy ML, Cieuta-Walti C, et al. Growth curves for French people with Down syndrome from birth to 20 years of age. Am J Med Genet A. 2018;176:2685–94. - PubMed
  16. Growth Hormone Research S. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J Clin Endocrinol Metab. 2000;85:3990–3. - PubMed
  17. Swillen A, McDonald-McGinn D. Developmental trajectories in 22q11.2 deletion. Am J Med Genet C Semin Med Genet. 2015;169:172–81. - PubMed
  18. McDonald-McGinn DM, Sullivan KE, Marino B, Philip N, Swillen A, Vorstman JA, et al. 22q11.2 deletion syndrome. Nat Rev Dis Prim. 2015;1:15071. - PubMed
  19. Van L, Boot E, Bassett AS. Update on the 22q11.2 deletion syndrome and its relevance to schizophrenia. Curr Opin Psychiatry. 2017;30:191–96. - PubMed
  20. Schneider M, Debbane M, Bassett AS, Chow EW, Fung WL, van den Bree M, 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. 2014;171:627–39. - PubMed
  21. Fiksinski AM, Breetvelt EJ, Duijff SN, Bassett AS, Kahn RS, Vorstman JA. Autism spectrum and psychosis risk in the 22q11.2 deletion syndrome. Findings from a prospective longitudinal study. Schizophr Res. 2017;188:59–62. - PubMed
  22. Vorstman JA, Morcus ME, Duijff SN, Klaassen PW. Heineman-de Boer JA, Beemer FA, et al. The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J Am Acad Child Adolesc Psychiatry. 2006;45:1104–13. - PubMed
  23. Duijff SN, Klaassen PW, de Veye HF, Beemer FA, Sinnema G, Vorstman JA. Cognitive development in children with 22q11.2 deletion syndrome. Br J Psychiatry. 2012;200:462–8. - PubMed
  24. Karayiorgou M, Simon TJ, Gogos JA. 22q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia. Nat Rev Neurosci. 2010;11:402–16. - PubMed
  25. Vorstman JA, Breetvelt EJ, Duijff SN, Eliez S, Schneider M, Jalbrzikowski M, et al. Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome. JAMA Psychiatry. 2015;72:377–85. - PubMed
  26. Cleynen I, Engchuan W, Hestand MS, Heung T, Holleman AM, Johnston HR, et al. Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion. Mol Psychiatry. https://doi.org/10.1038/s41380-020-0654-3 2020. - PubMed
  27. Gur RE, Bassett AS, McDonald-McGinn DM, Bearden CE, Chow E, Emanuel BS, et al. A neurogenetic model for the study of schizophrenia spectrum disorders: the International 22q11.2 Deletion Syndrome Brain Behavior Consortium. Mol Psychiatry. 2017;22:1664–72. - PubMed
  28. Wechsler D. Wechsler Adult Intelligence Scale—revised. The Psychological Corporation: San Antonio, TX; 1981. - PubMed
  29. Wechsler D. Wechsler Adult Intelligence Scale-III. The Psychological Corporation: San Antonio, TX; 1997. - PubMed
  30. Wechsler D. Wechsler Abbreviated Scale of Intelligence—Second Edition (WASI-II). NCS Pearson: San Antonio, TX; 2011. - PubMed
  31. Wechsler D. Wechsler Adult Intelligence Scale–Fourth Edition. Pearson: San Antonio, TX; 2008. - PubMed
  32. Wechsler D. The Wechsler preschool and primary scale of intelligence, Third Edition (WPPSI-III). The Psychological Corporation: San Antonio, TX; 2002 - PubMed
  33. Wechsler D. The Wechsler intelligence scale for children—third edition. The Psychological Corporation: San Antonio, Texas; 1991. - PubMed
  34. Wechsler D. Wechsler Intelligence Scale for Children–Fourth Edition. The Psychological Corporation: San Antonio, TX; 2003. - PubMed
  35. Association AP. Diagnostic and statistical manual of mental disorders (4th ed., Text Revision). Author: Washington, DC; 2000. - PubMed
  36. Chow EW, Watson M, Young DA, Bassett AS. Neurocognitive profile in 22q11 deletion syndrome and schizophrenia. Schizophr Res. 2006;87:270–8. - PubMed
  37. De Smedt B, Devriendt K, Fryns JP, Vogels A, Gewillig M, Swillen A. Intellectual abilities in a large sample of children with Velo-Cardio-Facial Syndrome: an update. J Intellect Disabil Res. 2007;51:666–70. - PubMed
  38. Fiksinski A, Heung T, Corral M, Breetvelt E, Costain G, Marshall C, et al. Within-family influences on dimensional neurobehavioral traits in a high-risk genetic model. Psychol Med. 2021:1–9. - PubMed
  39. Fiksinski AM, Schneider M, Murphy CM, Armando M, Vicari S, Canyelles JM, et al. Understanding the pediatric psychiatric phenotype of 22q11.2 deletion syndrome. Am J Med Genet A. 2018:1–10. - PubMed
  40. Bassett AS, McDonald-McGinn DM, Devriendt K, Digilio MC, Goldenberg P, Habel A, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011;159:332–9 e1. - PubMed
  41. Fung WL, Butcher NJ, Costain G, Andrade DM, Boot E, Chow EW, et al. Practical guidelines for managing adults with 22q11.2 deletion syndrome. Genet Med. 2015;17:599–609. - PubMed
  42. Swillen A, McDonald-McGinn D. Developmental trajectories in 22q11.2 deletion. Am J Med Genet Part C: Semin Med Genet. 2015;169:172–81. - PubMed
  43. MacCabe JH, Wicks S, Lofving S, David AS, Berndtsson A, Gustafsson JE, et al. Decline in cognitive performance between ages 13 and 18 years and the risk for psychosis in adulthood: a Swedish longitudinal cohort study in males. JAMA Psychiatry. 2013;70:261–70. - PubMed
  44. Mollon J, David AS, Zammit S, Lewis G, Reichenberg A. Course of cognitive development from infancy to early adulthood in the psychosis spectrum. JAMA Psychiatry. 2018;75:270–79. - PubMed
  45. Harvey PD, Bowie CR, Friedman JI. Cognition in schizophrenia. Curr Psychiatry Rep. 2001;3:423–8. - PubMed
  46. Keefe RSE, Kahn RS. Cognitive decline and disrupted cognitive trajectory in schizophrenia. JAMA Psychiatry 2017;74:535–36. - PubMed
  47. Sullivan PF, Owen MJ. Increasing the clinical psychiatric knowledge base about pathogenic copy number variation. Am J Psychiatry. 2020;177:204–09. - PubMed
  48. Chawner S, Doherty JL, Moss H, Niarchou M, Walters JTR, Owen MJ, et al. Childhood cognitive development in 22q11.2 deletion syndrome: case-control study. Br J Psychiatry. 2017;211:223–30. - PubMed
  49. Sansone SM, Schneider A, Bickel E, Berry-Kravis E, Prescott C, Hessl D. Improving IQ measurement in intellectual disabilities using true deviation from population norms. J Neurodev Disord. 2014;6:16. - PubMed
  50. Briegel W, Schneider M, Schwab KO. 22q11.2 deletion syndrome: behaviour problems of children and adolescents and parental stress. Child Care Health Dev. 2008;34:795–800. - PubMed
  51. Fiksinski AM, Breetvelt EJ, Lee YJ, Boot E, Butcher N, Palmer L, et al. Neurocognition and adaptive functioning in a genetic high risk model of schizophrenia. Psychol Med. 2018;49:1047–54. - PubMed
  52. Butcher NJ, Chow EW, Costain G, Karas D, Ho A, Bassett AS. Functional outcomes of adults with 22q11.2 deletion syndrome. Genet Med. 2012;14:836–43. - PubMed
  53. Moreno-De-Luca A, Evans DW, Boomer KB, Hanson E, Bernier R, Goin-Kochel RP, et al. The role of parental cognitive, behavioral, and motor profiles in clinical variability in individuals with chromosome 16p11.2 deletions. JAMA Psychiatry. 2015;72:119–26. - PubMed
  54. Huguet G, Schramm C, Douard E, Jiang L, Labbe A, Tihy F, et al. Measuring and estimating the effect sizes of copy number variants on general intelligence in community-based samples. JAMA Psychiatry. 2018;75:447–57. - PubMed
  55. Davies RW, Fiksinski AM, Breetvelt EJ, Williams NM, Hooper SR, Monfeuga T, et al. Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome. Nat Med. 2020;26:1912–18. - PubMed

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