Skip to main content
Top
Published in: European Child & Adolescent Psychiatry 6/2014

Open Access 01-06-2014 | Original Contribution

Clinical and cognitive risk factors for psychotic symptoms in 22q11.2 deletion syndrome: a transversal and longitudinal approach

Authors: Maude Schneider, Marie Schaer, A. Kadir Mutlu, Sarah Menghetti, Bronwyn Glaser, Martin Debbané, Stephan Eliez

Published in: European Child & Adolescent Psychiatry | Issue 6/2014

Login to get access

Abstract

22q11.2 deletion syndrome (22q11DS) is associated with increased risk for schizophrenia. Better identifying risk factors for the emergence of psychotic symptoms in this population is needed to improve clinical assessment and early interventions. Schizophrenia spectrum disorders, hallucinations and delusions were characterized in an original sample of 104 individuals with 22q11DS. Further analysis of positive and negative symptoms was performed in a subsample of 59 individuals. Finally, longitudinal data available in 56 patients were used to explore the developmental trajectories of psychotic symptoms as well as the associations between psychotic symptoms and cognitive functioning. Schizophrenia spectrum disorders and psychotic symptoms were frequent in adolescent and adults with 22q11DS. The severity of hallucinations and non-persecutory delusional ideas discriminated patients at ultra-high risk for conversion to psychosis. Whereas approximately one-third of patients experienced an emergence of psychotic symptoms during a 4-year interval, 20 % displayed transient symptoms. Individuals with psychotic symptoms were characterized by a lower cognitive functioning in the context of the 22q11DS. The present study adds important data on the characteristics and developmental trajectory of psychotic symptoms in this population. This information may ultimately help clinicians dealing with these patients to reduce the duration of untreated psychosis and improve outcome.
Literature
1.
go back to reference Murphy K, Jones L, Owen M (1999) High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry 56(10):940–945PubMedCrossRef Murphy K, Jones L, Owen M (1999) High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry 56(10):940–945PubMedCrossRef
2.
go back to reference WHO (1996) Schizophrenia and public health. Nations for mental health WHO (1996) Schizophrenia and public health. Nations for mental health
3.
go back to reference Debbané M, Glaser B, David MK, Feinstein C, Eliez S (2006) Psychotic symptoms in children and adolescents with 22q11.2 deletion syndrome: neuropsychological and behavioral implications. Schizophr Res 84(2–3):187–193PubMedCrossRef Debbané M, Glaser B, David MK, Feinstein C, Eliez S (2006) Psychotic symptoms in children and adolescents with 22q11.2 deletion syndrome: neuropsychological and behavioral implications. Schizophr Res 84(2–3):187–193PubMedCrossRef
4.
go back to reference Gothelf D, Feinstein C, Thompson T, Gu E, Penniman L, Van Stone E, Kwon H, Eliez S, Reiss AL (2007) Risk factors for the emergence of psychotic disorders in adolescents with 22q11.2 deletion syndrome. Am J Psych 164(4):663–669CrossRef Gothelf D, Feinstein C, Thompson T, Gu E, Penniman L, Van Stone E, Kwon H, Eliez S, Reiss AL (2007) Risk factors for the emergence of psychotic disorders in adolescents with 22q11.2 deletion syndrome. Am J Psych 164(4):663–669CrossRef
5.
go back to reference Armando M, Girardi P, Vicari S, Menghini D, Digilio MC, Pontillo M, Saba R, Mazzone L, Lin A, Klier CM, Schäfer MR, Amminger GP (2012) Adolescents at ultra-high risk for psychosis with and without 22q11 deletion syndrome: a comparison of prodromal psychotic symptoms and general functioning. Schizophr Res 139(1–3):151–156PubMedCrossRef Armando M, Girardi P, Vicari S, Menghini D, Digilio MC, Pontillo M, Saba R, Mazzone L, Lin A, Klier CM, Schäfer MR, Amminger GP (2012) Adolescents at ultra-high risk for psychosis with and without 22q11 deletion syndrome: a comparison of prodromal psychotic symptoms and general functioning. Schizophr Res 139(1–3):151–156PubMedCrossRef
6.
go back to reference Schneider M, Van der Linden M, Glaser B, Rizzi E, Dahoun SP, Hinard C, Bartoloni L, Antonarakis SE, Debbané M, Eliez S (2012) Preliminary structure and predictive value of attenuated negative symptoms in 22q11.2 deletion syndrome. Psychiat Res 196:277–284CrossRef Schneider M, Van der Linden M, Glaser B, Rizzi E, Dahoun SP, Hinard C, Bartoloni L, Antonarakis SE, Debbané M, Eliez S (2012) Preliminary structure and predictive value of attenuated negative symptoms in 22q11.2 deletion syndrome. Psychiat Res 196:277–284CrossRef
7.
go back to reference Lucas S, Fitzgerald D, Redoblado-Hodge MA, Anderson J, Sanbrook M, Harris A, Brennan J (2004) Neuropsychological correlates of symptom profiles in first episode schizophrenia. Schizophr Res 71(2–3):323–330PubMedCrossRef Lucas S, Fitzgerald D, Redoblado-Hodge MA, Anderson J, Sanbrook M, Harris A, Brennan J (2004) Neuropsychological correlates of symptom profiles in first episode schizophrenia. Schizophr Res 71(2–3):323–330PubMedCrossRef
8.
go back to reference Rhinewine JP, Lencz T, Thaden EP, Cervellione KL, Burdick KE, Henderson I, Bhaskar S, Keehlisen L, Kane J, Kohn N, Fisch GS, Bilder RM, Kumra S (2005) Neurocognitive profile in adolescents with early-onset schizophrenia: clinical correlates. Biol Psychiatry 58(9):705–712PubMedCrossRef Rhinewine JP, Lencz T, Thaden EP, Cervellione KL, Burdick KE, Henderson I, Bhaskar S, Keehlisen L, Kane J, Kohn N, Fisch GS, Bilder RM, Kumra S (2005) Neurocognitive profile in adolescents with early-onset schizophrenia: clinical correlates. Biol Psychiatry 58(9):705–712PubMedCrossRef
9.
go back to reference Becker HE, Nieman DH, Wiltink S, Dingemans PM, van de Fliert JR, Velthorst E, de Haan L, van Amelsvoort TA, Linszen DH (2010) Neurocognitive functioning before and after the first psychotic episode: does psychosis result in cognitive deterioration? Psychol Med 40(10):1599–1606PubMedCrossRef Becker HE, Nieman DH, Wiltink S, Dingemans PM, van de Fliert JR, Velthorst E, de Haan L, van Amelsvoort TA, Linszen DH (2010) Neurocognitive functioning before and after the first psychotic episode: does psychosis result in cognitive deterioration? Psychol Med 40(10):1599–1606PubMedCrossRef
10.
go back to reference Keefe RSE, Perkins DO, Gu H, Zipursky RB, Christensen BK, Lieberman JA (2006) A longitudinal study of neurocognitive function in individuals at-risk for psychosis. Schizophr Res 88(1–3):26–35PubMedCrossRef Keefe RSE, Perkins DO, Gu H, Zipursky RB, Christensen BK, Lieberman JA (2006) A longitudinal study of neurocognitive function in individuals at-risk for psychosis. Schizophr Res 88(1–3):26–35PubMedCrossRef
11.
go back to reference Lencz T, Smith CW, McLaughlin D, Auther A, Nakayama E, Hovey L, Cornblatt BA (2006) Generalized and specific neurocognitive deficits in prodromal schizophrenia. Biol Psychiatry 59(9):863–871PubMedCrossRef Lencz T, Smith CW, McLaughlin D, Auther A, Nakayama E, Hovey L, Cornblatt BA (2006) Generalized and specific neurocognitive deficits in prodromal schizophrenia. Biol Psychiatry 59(9):863–871PubMedCrossRef
12.
go back to reference Frommann I, Pukrop R, Brinkmeyer J, Bechdolf A, Ruhrmann S, Berning J, Decker P, Riedel M, Möller H-J, Wölwer W, Gaebel W, Klosterkötter J, Maier W, Wagner M (2011) Neuropsychological profiles in different at-risk states of psychosis: executive control impairment in the early- and additional memory dysfunction in the late-prodromal state. Schizophr Bull 37(4):861–873PubMedCentralPubMedCrossRef Frommann I, Pukrop R, Brinkmeyer J, Bechdolf A, Ruhrmann S, Berning J, Decker P, Riedel M, Möller H-J, Wölwer W, Gaebel W, Klosterkötter J, Maier W, Wagner M (2011) Neuropsychological profiles in different at-risk states of psychosis: executive control impairment in the early- and additional memory dysfunction in the late-prodromal state. Schizophr Bull 37(4):861–873PubMedCentralPubMedCrossRef
13.
go back to reference Antshel KM, Shprintzen R, Fremont W, Higgins AM, Faraone SV, Kates WR (2010) Cognitive and psychiatric predictors to psychosis in velocardiofacial syndrome: a 3-year follow-up study. J Am Acad Child Adolesc Psychiatry 49(4):333–344PubMedCentralPubMed Antshel KM, Shprintzen R, Fremont W, Higgins AM, Faraone SV, Kates WR (2010) Cognitive and psychiatric predictors to psychosis in velocardiofacial syndrome: a 3-year follow-up study. J Am Acad Child Adolesc Psychiatry 49(4):333–344PubMedCentralPubMed
14.
go back to reference Gothelf D, Eliez S, Thompson T, Hinard C, Penniman L, Feinstein C, Kwon H, Jin S, Jo B, Antonarakis SE, Morris MA, Reiss AL (2005) COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome. Nat Neurosci 8(11):1500–1502PubMedCrossRef Gothelf D, Eliez S, Thompson T, Hinard C, Penniman L, Feinstein C, Kwon H, Jin S, Jo B, Antonarakis SE, Morris MA, Reiss AL (2005) COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome. Nat Neurosci 8(11):1500–1502PubMedCrossRef
15.
go back to reference Green T, Gothelf D, Glaser B, Debbane M, Frisch A, Kotler M, Weizman A, Eliez S (2009) Psychiatric disorders and intellectual functioning throughout development in velocardiofacial (22q11.2 deletion) syndrome. J Am Acad Child Adolesc Psychiatry 48(11):1060–1068PubMedCrossRef Green T, Gothelf D, Glaser B, Debbane M, Frisch A, Kotler M, Weizman A, Eliez S (2009) Psychiatric disorders and intellectual functioning throughout development in velocardiofacial (22q11.2 deletion) syndrome. J Am Acad Child Adolesc Psychiatry 48(11):1060–1068PubMedCrossRef
16.
go back to reference Shapiro DI, Cubells JF, Ousley OY, Rockers K, Walker EF (2011) Prodromal symptoms in adolescents with 22q11.2 deletion syndrome and schizotypal personality disorder. Schizophr Res 129(1):20–28PubMedCentralPubMedCrossRef Shapiro DI, Cubells JF, Ousley OY, Rockers K, Walker EF (2011) Prodromal symptoms in adolescents with 22q11.2 deletion syndrome and schizotypal personality disorder. Schizophr Res 129(1):20–28PubMedCentralPubMedCrossRef
17.
go back to reference Schaer M, Debbané M, Bach Cuadra M, Ottet M-C, Glaser B, Thiran J-P, Eliez S (2009) Deviant trajectories of cortical maturation in 22q11.2 deletion syndrome (22q11DS): a cross-sectional and longitudinal study. Schizophr Res 115(2–3):182–190PubMedCrossRef Schaer M, Debbané M, Bach Cuadra M, Ottet M-C, Glaser B, Thiran J-P, Eliez S (2009) Deviant trajectories of cortical maturation in 22q11.2 deletion syndrome (22q11DS): a cross-sectional and longitudinal study. Schizophr Res 115(2–3):182–190PubMedCrossRef
18.
go back to reference Reich W (2000) Diagnostic interview for children and adolescents (DICA). J Am Acad Child Adolesc Psychiatry 39:59–66PubMedCrossRef Reich W (2000) Diagnostic interview for children and adolescents (DICA). J Am Acad Child Adolesc Psychiatry 39:59–66PubMedCrossRef
19.
go back to reference First M, Spitzer R, Gibbon M, Williams J (1996) Structured clinical interview for the DSM-IV-TR axis I disorders (SCID-I). Biometrics Research, New York State Psychiatric Institute, New York First M, Spitzer R, Gibbon M, Williams J (1996) Structured clinical interview for the DSM-IV-TR axis I disorders (SCID-I). Biometrics Research, New York State Psychiatric Institute, New York
20.
go back to reference Kaufman J, Birmaher B, Brent D, Rao U (1997) Schedule for affective disorders and schizophrenia for school-age children-present lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 36:980–988PubMedCrossRef Kaufman J, Birmaher B, Brent D, Rao U (1997) Schedule for affective disorders and schizophrenia for school-age children-present lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 36:980–988PubMedCrossRef
21.
go back to reference McGlashan TH, Miller TJ, Woods SW (2001) Structured Interview for Prodromal Syndromes (SIPS; Version 3.0, unpublished manuscript). PRIME Research Clinic, Yale University, School of Medicine, New Heaven, Connecticut McGlashan TH, Miller TJ, Woods SW (2001) Structured Interview for Prodromal Syndromes (SIPS; Version 3.0, unpublished manuscript). PRIME Research Clinic, Yale University, School of Medicine, New Heaven, Connecticut
22.
go back to reference Miller TJ, McGlashan TH, Rosen JL, Cadenhead K, Cannon T, Ventura J, McFarlane W, Perkins DO, Pearlson GD, Woods SW (2003) Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophr Bull 29(4):703–715PubMedCrossRef Miller TJ, McGlashan TH, Rosen JL, Cadenhead K, Cannon T, Ventura J, McFarlane W, Perkins DO, Pearlson GD, Woods SW (2003) Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophr Bull 29(4):703–715PubMedCrossRef
23.
go back to reference Overall J, Gorham D (1962) The brief psychiatric rating scale. Psychol Rep 10:799–812CrossRef Overall J, Gorham D (1962) The brief psychiatric rating scale. Psychol Rep 10:799–812CrossRef
24.
go back to reference Nicholson IR, Chapman JE, Neufeld RW (1995) Variability in BPRS definitions of positive and negative symptoms. Schizophr Res 17(2):177–185PubMedCrossRef Nicholson IR, Chapman JE, Neufeld RW (1995) Variability in BPRS definitions of positive and negative symptoms. Schizophr Res 17(2):177–185PubMedCrossRef
25.
go back to reference Wechsler D (1991) Wechsler Intelligence Scale for Children, 3rd edn. Manual. The Psychological Corporation, San Antonio Wechsler D (1991) Wechsler Intelligence Scale for Children, 3rd edn. Manual. The Psychological Corporation, San Antonio
26.
go back to reference Cohen M (1997) Children’s memory scale. The Psychological Corporation, London Cohen M (1997) Children’s memory scale. The Psychological Corporation, London
27.
go back to reference Wechsler D (1997) Wechsler Adult Intelligence Scale, 3rd edn. Administration and scoring manual. The Psychological Corporation, San Antonio Wechsler D (1997) Wechsler Adult Intelligence Scale, 3rd edn. Administration and scoring manual. The Psychological Corporation, San Antonio
28.
go back to reference Wechsler D (1987) Manual for the Wechsler Memory Scale—revised. The Psychological Corporation, San Antonio Wechsler D (1987) Manual for the Wechsler Memory Scale—revised. The Psychological Corporation, San Antonio
29.
go back to reference Dedrick RF, Ferron JM, Hess MR, Hogarty KY, Kromrey JD, Lang TR, Niles JD, Lee RS (2009) Multilevel modeling: a review of methodological issues and applications. Rev Educ Res 79:69–102CrossRef Dedrick RF, Ferron JM, Hess MR, Hogarty KY, Kromrey JD, Lang TR, Niles JD, Lee RS (2009) Multilevel modeling: a review of methodological issues and applications. Rev Educ Res 79:69–102CrossRef
30.
go back to reference Peng H, Lu Y (2012) Model selection in linear mixed effect models. J Multivariate Anal 109:109–129CrossRef Peng H, Lu Y (2012) Model selection in linear mixed effect models. J Multivariate Anal 109:109–129CrossRef
31.
go back to reference Baker KD, Skuse DH (2005) Adolescents and young adults with 22q11 deletion syndrome: psychopathology in an at-risk group. Br J Psychiatry 186:115–120PubMedCrossRef Baker KD, Skuse DH (2005) Adolescents and young adults with 22q11 deletion syndrome: psychopathology in an at-risk group. Br J Psychiatry 186:115–120PubMedCrossRef
32.
go back to reference Vorstman JAS, Morcus MEJ, Duijff SN, Klaassen PWJ, Heineman-de Boer JA, Beemer FA, Swaab H, Kahn RS, van Engeland H (2006) The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J Am Acad Child Adolesc Psychiatry 45 (9):1104–1113 Vorstman JAS, Morcus MEJ, Duijff SN, Klaassen PWJ, Heineman-de Boer JA, Beemer FA, Swaab H, Kahn RS, van Engeland H (2006) The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J Am Acad Child Adolesc Psychiatry 45 (9):1104–1113
33.
go back to reference Kumra S (2008) Digging deeper using neuroimaging tools reveals important clues to early-onset schizophrenia. J Am Acad Child Adolesc Psychiatry 47(10):1103–1104PubMedCrossRef Kumra S (2008) Digging deeper using neuroimaging tools reveals important clues to early-onset schizophrenia. J Am Acad Child Adolesc Psychiatry 47(10):1103–1104PubMedCrossRef
34.
go back to reference Marshall M, Lewis S, Lockwood A, Drake R, Jones P, Croudace T (2005) Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review. Arch Gen Psychiatry 62(9):975–983PubMedCrossRef Marshall M, Lewis S, Lockwood A, Drake R, Jones P, Croudace T (2005) Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review. Arch Gen Psychiatry 62(9):975–983PubMedCrossRef
35.
go back to reference Garety PA, Kuipers E, Fowler D, Freeman D, Bebbington PE (2001) A cognitive model of the positive symptoms of psychosis. Psychol Med 31(2):189–195PubMedCrossRef Garety PA, Kuipers E, Fowler D, Freeman D, Bebbington PE (2001) A cognitive model of the positive symptoms of psychosis. Psychol Med 31(2):189–195PubMedCrossRef
36.
go back to reference Dominguez MG, Saka MC, can Saka M, Lieb R, Wittchen HU, van Os J (2010) Early expression of negative/disorganized symptoms predicting psychotic experiences and subsequent clinical psychosis: a 10-year study. Am J Psych 167 (9):1075–1082 Dominguez MG, Saka MC, can Saka M, Lieb R, Wittchen HU, van Os J (2010) Early expression of negative/disorganized symptoms predicting psychotic experiences and subsequent clinical psychosis: a 10-year study. Am J Psych 167 (9):1075–1082
37.
go back to reference Riecher-Rössler A, Pflueger MO, Aston J, Borgwardt SJ, Brewer WJ, Gschwandtner U, Stieglitz R-D (2009) Efficacy of using cognitive status in predicting psychosis: a 7-year follow-up. Biol Psychiatry 66(11):1023–1030PubMedCrossRef Riecher-Rössler A, Pflueger MO, Aston J, Borgwardt SJ, Brewer WJ, Gschwandtner U, Stieglitz R-D (2009) Efficacy of using cognitive status in predicting psychosis: a 7-year follow-up. Biol Psychiatry 66(11):1023–1030PubMedCrossRef
38.
go back to reference Velthorst E, Nieman DH, Becker HE, van de Fliert R, Dingemans PM, Klaassen R, de Haan L, van Amelsvoort T, Linszen DH (2009) Baseline differences in clinical symptomatology between ultra high risk subjects with and without a transition to psychosis. Schizophr Res 109(1–3):60–65PubMedCrossRef Velthorst E, Nieman DH, Becker HE, van de Fliert R, Dingemans PM, Klaassen R, de Haan L, van Amelsvoort T, Linszen DH (2009) Baseline differences in clinical symptomatology between ultra high risk subjects with and without a transition to psychosis. Schizophr Res 109(1–3):60–65PubMedCrossRef
39.
go back to reference Duijff SN, Klaassen PWJ, de Veye HFNS, Beemer FA, Sinnema G, Vorstman JAS (2012) Cognitive development in children with 22q11.2 deletion syndrome. Br J Psychiatry 200:462–468PubMedCrossRef Duijff SN, Klaassen PWJ, de Veye HFNS, Beemer FA, Sinnema G, Vorstman JAS (2012) Cognitive development in children with 22q11.2 deletion syndrome. Br J Psychiatry 200:462–468PubMedCrossRef
40.
go back to reference Beaton EA, Simon TJ (2011) How might stress contribute to increased risk for schizophrenia in children with chromosome 22q11.2 deletion syndrome? J Neurodev Disord 3(1):68–75PubMedCentralPubMedCrossRef Beaton EA, Simon TJ (2011) How might stress contribute to increased risk for schizophrenia in children with chromosome 22q11.2 deletion syndrome? J Neurodev Disord 3(1):68–75PubMedCentralPubMedCrossRef
41.
go back to reference Bassett AS, McDonald-McGinn DM, Devriendt K, Digilio MC, Goldenberg P, Habel A, Marino B, Oskarsdottir S, Philip N, Sullivan K, Swillen A, Vorstman J (2011) Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr 159(2):332–339PubMedCentralPubMedCrossRef Bassett AS, McDonald-McGinn DM, Devriendt K, Digilio MC, Goldenberg P, Habel A, Marino B, Oskarsdottir S, Philip N, Sullivan K, Swillen A, Vorstman J (2011) Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr 159(2):332–339PubMedCentralPubMedCrossRef
Metadata
Title
Clinical and cognitive risk factors for psychotic symptoms in 22q11.2 deletion syndrome: a transversal and longitudinal approach
Authors
Maude Schneider
Marie Schaer
A. Kadir Mutlu
Sarah Menghetti
Bronwyn Glaser
Martin Debbané
Stephan Eliez
Publication date
01-06-2014
Publisher
Springer Berlin Heidelberg
Published in
European Child & Adolescent Psychiatry / Issue 6/2014
Print ISSN: 1018-8827
Electronic ISSN: 1435-165X
DOI
https://doi.org/10.1007/s00787-013-0469-8

Other articles of this Issue 6/2014

European Child & Adolescent Psychiatry 6/2014 Go to the issue