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22q11.2 Deletion Syndrome and Schizophrenia in Children and Adolescents
multifactorial account that outlines the different routes psychosis- psychotic symptoms in youths with 22q11DS but help to prevent their
proneness may employ in the unfolding of clinically relevant psychotic development into clinical states of psychosis. ■
phenomena. We feel that the high prevalence of schizophrenia in
22q11DS is best represented by the wealth of risk factors associated Acknowledgements
with the neurogenetic syndrome in terms of genetic, neuroanatomical, Important thanks go to the Swiss and French 22q11DS parent
cognitive and affective concerns. Clearly, more investigations associations, Connect22 and Generation 22, without which this article
concerning the multiple risk-factor interactions are necessary, some of would not have been possible. We also wish to thank Bronwyn Glaser
which may investigate complex processes such as brain maturation and Marie Schaer for their ongoing collaboration and contributions.
and the unfolding of hallucinations, while others further examine This research process was supported by research grants to Stephan
higher-order cognitive functions such as social cognition in relation to Eliez from the Swiss National Fund for Research (PP00B-102864), the
the elaboration of a delusional belief system. These may yield NARSAD Foundation (2002 Lieber Investigator Award) and the
preventative treatment strategies that acknowledge the expression of Academic Society of Geneva.
1. Murphy KC, Jones LA, Owen MJ, High rates of schizophrenia in 1995;25(4):739–53. 41. Simon TJ, Ding L, Bish JP, et al., Volumetric, connective, and
adults with velo-cardio-facial syndrome, Arch Gen Psychiatry, 22. DiDuca D, Joseph S, Assessing schizotypal traits in 13–18 year morphologic changes in the brains of children with chromosome
1999;56(10):940–45. olds: Revising the JSS, Pers Individ Dif, 1999;27:673–82. 22q11.2 deletion syndrome: An integrative study, Neuroimage,
2. Pulver AE, Nestadt G, Goldberg R, et al., Psychotic illness in the 23. Kaufman J, Birmaher B, Brent D, et al., Schedule for affective 2005;25(1):169–80.
patients diagnosed with velo-cardio-facial syndrome and their disorders and schizophrenia for school-age children—present 42. Dufour F, Schaer M, Debbané M, et al., Cingulate gyral
relatives, J Nerv Ment Dis, 1994;182:476–8. and lifetime version (k-sads-pl): Initial reliability and validity reductions associated with low executive functioning and
3. Shprintzen RJ, Goldberg R, Golding-Kushner KJ, Marion RW, data, J Am Acad Child Adolesc Psychiatry, 1997;36(7):980–88.. psychotic symptoms in 22q11.2 deletion syndrome; under
Late-onset psychosis in the velo-cardio-facial syndrome, Am J Med 24. Vorstman JA, Morcus ME, Duijff SN, et al., The 22q11.2 deletion review.
Genet, 1992;42(1):141–2. in children: High rate of autistic disorders and early onset of 43. Schaer M, Debbané M, Bach Cuadra M, et al., Cortical thickness
4. Karayiorgou M, Morris MA, Morrow B, et al., Schizophrenia psychotic symptoms, J Am Acad Child Adolesc Psychiatry, in 22q11 deletion syndrome: Alterations in affected children and
susceptibility associated with interstitial deletions of 2006;45(9):1104–13. evolution into adulthood, Schizophr Res, 2008;130(Suppl.).
chromosome 22q11, Proc Natl Acad Sci U S A, 1995;92(17): 25. Debbané M, Glaser B, David MK, et al., Psychotic symptoms in 44. Lewandowski KE, Shashi V, Berry PM, Kwapil TR, Schizophrenic-
7612–16. children and adolescents with 22q11.2 deletion syndrome: like neurocognitive deficits in children and adolescents with
5. Gothelf D, Frisch A, Munitz H, et al., Velocardiofacial Neuropsychological and behavioral implications, Schizophr Res, 22q11 deletion syndrome, Am J Med Genet B Neuropsychiatr Genet,
manifestations and microdeletions in schizophrenic inpatients, 2006;84(2–3):187–93. 2007;144(1):27–36.
Am J Med Genet, 1997;72(4):455–61. 26. Frith C, The neural basis of hallucinations and delusions, 45. van Amelsvoort T, Henry J, Morris R, et al., Cognitive deficits
6. Sporn A, Addington A, Reiss AL, et al., 22q11 deletion C R Biol, 2005;328(2):169–75. associated with schizophrenia in velo-cardio-facial syndrome,
syndrome in childhood onset schizophrenia: An update, 27. Johns LC, McGuire PK, Verbal self-monitoring and auditory Schizophr Res, 2004;70(2–3):223–32.
Mol Psychiatry, 2004;9(3):225–6. hallucinations in schizophrenia, Lancet, 1999;353(9151): 46. Eliez S, van Amelsvoort T, Neuroimaging in velo-cardio-facial
7. Murphy KC, Annotation: Velo-cardio-facial syndrome, J Child 469–70. syndrome. In Scambler KM (ed.), Velo-cardio-facial syndrome:
Psychol Psychiatry, 2005;46(6):563–71. 28. Keefe RS, Arnold MC, Bayen UJ, Harvey PD, Source monitoring A model for understanding microdeletion disorders, Cambridge:
8. Rapoport JL, Addington AM, Frangou S, Psych MR, The deficits in patients with schizophrenia; a multinomial modelling University Press, 2005;165–80.
neurodevelopmental model of schizophrenia: Update 2005, analysis, Psychol Med, 1999;29(4):903–14. 47. Williams NM, O’Donovan MC, Owen MJ, Chromosome 22
Mol Psychiatry, 2005;10:434–49. 29. Brébion G, Gorman JM, Malaspina D, Amador X, A model of deletion syndrome and schizophrenia, Int Rev Neurobiol,
9. Johns LC, van Os J, The continuity of psychotic experiences in verbal memory impairments in schizophrenia: Two systems and 2006;73:1–27.
the general population, Clin Psychol Rev, 2001;21(8):1125–41. their associations with underlying cognitive processes and 48. Maher BA, Delusional thinking and perceptual disorder, J Individ
10. Garralda ME, Hallucinations in children with conduct and clinical symptoms, Psychol Med, 2005;35(1):133–42. Psychol, 1974;30:98–113.
emotional disorders: II. The follow-up study, Psychol Med, 30. Larøi F, Collignon O, Van der Linden M, Source monitoring for 49. Birchwood M, MacMillan F, Smith J, Early intervention. In
1984;14(3):597–604. actions in hallucination proneness, Cognit Neuropsychiatry, Birchwood M, Tarrier N (eds), Innovations in the psychological
11. Larøi F, Van der Linden M, Goëb J-L, Hallucinations and 2005;10(2):105–23. management of schizophrenia, Chichester: Wiley, 1993;115–45.
delusions in children and adolescents, Curr Psychiatry Rev, 31. Debbané M, Van der Linden M, Glaser B, Eliez S, Source 50. Yung AR, McGorry PD, The prodromal phase of first-episode
2006;2(4):473–85. monitoring for actions in adolescents with 22q11.2 deletion psychosis: Past and current conceptualizations, Schizophr Bull,
12. van Os J, Verdoux H, Maurice-Tison S, et al., Self-reported syndrome (22q11ds), Psychol Med, 2007;1–10. 1996;22(2):353–70.
psychosis-like symptoms and the continuum of psychosis, 32. Debbané M, Van der Linden M, Gex-Fabry M, Eliez S, Cognitive 51. Wells A, A metacognitive model and therapy for generalized
Soc Psychiatry Psychiatr Epidemiol, 1999;34(9):459–63. and emotional associations to positive schizotypy during anxiety disorder, Clin Psychol Psychother, 1999;6:86–95.
13. Poulton R, Caspi A, Moffitt TE, et al., Children’s self-reported adolescence, J Child Psychol Psychiatry, in press. 52. Morrison AP, French P, Wells, A, Metacognitive beliefs across
psychotic symptoms and adult schizophreniform disorder: A 33. Aleman A, Larøi F, Hallucinations: The science of idiosyncratic perception, the continuum of psychosis: Comparisons between patients with
15-year longitudinal study, Arch Gen Psychiatry, 2000;57(11): Washington: American Psychological Association, 2008. psychotic disorders, patients at ultra-high risk and non-patients,
1053–8. 34. Baker CA, Morrison AP, Cognitive processes in auditory Behav Res Ther, 2007;45(9):2241–6.
14. Johnstone EC, Owens DG, Hoare P, et al., Schizotypal cognitions hallucinations: Attributional biases and metacognition, Psychol 53. Gothelf D, Eliez S, Thompson T, et al., Comt genotype predicts
as a predictor of psychopathology in adolescents with mild Med, 1998;28(5):1199–1208. longitudinal cognitive decline and psychosis in 22q11.2 deletion
intellectual impairment, Br J Psychiatry, 2007;191:484–92. 35. Larøi F, Van der Linden M, Marczewski P, The effects of syndrome, Nat Neurosci, 2005;8(11):1500–1502.
15. Johnstone EC, Ebmeier KP, Miller P, et al., Predicting emotional salience, cognitive effort and meta-cognitive beliefs 54. Achenbach TM, Manual for the child behavior checklist/4-18 and 1991
schizophrenia: Findings from the edinburgh high-risk study, on a reality monitoring task in hallucination-prone subjects, Br J profile, Burlington, VT: University of Vermont, Department of
Br J Psychiatry, 2005;186:18–25. Clin Psychol, 2004;43(Pt 3):221–33. Psychiatry, 1991.
16. Miller P, Lawrie SM, Byrne M, et al., Self-rated schizotypal 36. Morrison AP, Haddock G, Cognitive factors in source monitoring 55. Overall JE, Gorham DR, The brief psychiatric rating scale (bprs):
cognitions, psychotic symptoms and the onset of schizophrenia and auditory hallucinations, Psychol Med, 1997;27(3):669–79. Recent developments in ascertainment and scaling,
in young people at high risk of schizophrenia, Acta Psychiatr Scand, 37. Allen P, Amaro E, Fu CH, et al., Neural correlates of the Psychopharmacological Bulletin, 1988;(24):97–9.
2002;105(5):341–5. misattribution of speech in schizophrenia, Br J Psychiatry, 56. Freeman D, Garety PA, Connecting neurosis and psychosis: The
17. Gothelf D, Feinstein C, Thompson T, et al., Risk factors for the 2007;190:162–9. direct influence of emotion on delusions and hallucinations,
emergence of psychotic disorders in adolescents with 22q11.2 38. McGuire PK, Silbersweig DA, Wright I, et al., The neural Behav Res Ther, 2003;41(8):923–47.
deletion syndrome, Am J Psychiatry, 2007;164(4):663–9. correlates of inner speech and auditory verbal imagery in 57. Trower P, Chadwick P, Pathways to defense of the self: A theory
18. Frith CD, The cognitive neuropsychology of schizophrenia, Hove: schizophrenia: Relationship to auditory verbal hallucinations, of two types of paranoia, Clinical Psychology: Science and Practice,
Psychology Press Ltd, 1992. Br J Psychiatry, 1996;169(2):148–59. 1995;2:263–78.
19. Freeman D, Garety PA, Kuipers E, et al., A cognitive model of 39. Gothelf D, Penniman L, Gu E, et al., Developmental trajectories 58. Feinstein C, Eliez S, Blasey C, Reiss AL, Psychiatric disorders and
persecutory delusions, Br J Clin Psychol, 2002;41(Pt 4):331–47. of brain structure in adolescents with 22q11.2 deletion behavioral problems in children with velocardiofacial syndrome:
20. Baker KD, Skuse DH, Adolescents and young adults with 22q11 syndrome: A longitudinal study, Schizophr Res, 2007;96:72–81. Usefulness as phenotypic indicators of schizophrenia risk, Biol
deletion syndrome: Psychopathology in an at-risk group, Br J 40. Kates WR, Miller AM, Abdulsabur N, et al., Temporal lobe Psychiatry, 2002;51(4):312–18.
Psychiatry, 2005;186:115–20. anatomy and psychiatric symptoms in velocardiofacial syndrome 59. Williams NM, Owen MJ, Genetic abnormalities of chromosome
21. Angold A, Prendergast M, Cox A, et al., The child and (22q11.2 deletion syndrome), J Am Acad Child Adolesc Psychiatry, 22 and the development of psychosis, Curr Psychiatry Rep,
adolescent psychiatric assessment (CAPA), Psychol Med, 2006;45(5):587–95. 2004;6(3):176–82.
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