Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome

Stefano Vicari; Jacob A.S. Vorstman; Elemi J. Breetvelt; Sasja N. Duijff; Stephan Eliez; Maude Schneider; Maria Jalbrzikowski; Marco Armando; Vandana Shashi; Stephen R. Hooper; Eva W.C. Chow; Wai Lun Alan Fung; Nancy J. Butcher; Donald A. Young; Donna M. Mcdonald-Mcginn; Annick Vogels; Therese Van Amelsvoort; Doron Gothelf; Ronnie Weinberger; Abraham Weizman; Petra W.J. Klaassen; Sanne Koops; Wendy R. Kates; Kevin M. Antshel; Tony J. Simon; Opal Y. Ousley; Ann Swillen; Raquel E. Gur; Carrie E. Bearden; René S. Kahn; Anne S. Bassett; Beverly S. Emanuel; Elaine H. Zackai; Leila Kushan; Wanda Fremont; Kelly Schoch; Joel Stoddard; Joseph Cubells; Fiona Fu; Linda E. Campbell; Rosemarie Fritsch; Elfi Vergaelen; Marjolein Neeleman; Erik Boot; Martin Debbané; Nicole Philip; Tamar Green; Marianne B.M. Van Denbree; Declan Murphy; Jaume Morey Canyelles; Celso Arango; Kieran C. Murphy; Maria Pontillo

doi:10.1001/jamapsychiatry.2014.2671

Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome

Stefano Vicari, Jacob A.S. Vorstman, Elemi J. Breetvelt, Sasja N. Duijff, Stephan Eliez, Maude Schneider, Maria Jalbrzikowski, Marco Armando, Vandana Shashi, Stephen R. Hooper, Eva W.C. Chow, Wai Lun Alan Fung, Nancy J. Butcher, Donald A. Young, Donna M. Mcdonald-Mcginn, Annick Vogels, Therese Van Amelsvoort, Doron Gothelf, Ronnie Weinberger, Abraham WeizmanPetra W.J. Klaassen, Sanne Koops, Wendy R. Kates, Kevin M. Antshel, Tony J. Simon, Opal Y. Ousley, Ann Swillen, Raquel E. Gur, Carrie E. Bearden, René S. Kahn, Anne S. Bassett, Beverly S. Emanuel, Elaine H. Zackai, Leila Kushan, Wanda Fremont, Kelly Schoch, Joel Stoddard, Joseph Cubells, Fiona Fu, Linda E. Campbell, Rosemarie Fritsch, Elfi Vergaelen, Marjolein Neeleman, Erik Boot, Martin Debbané, Nicole Philip, Tamar Green, Marianne B.M. Van Denbree, Declan Murphy, Jaume Morey Canyelles, Celso Arango, Kieran C. Murphy, Maria Pontillo

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Abstract

Importance: Patients with 22q11.2 deletion syndrome (22q11DS) have an elevated (25%) risk of developing schizophrenia. Recent reports have suggested that a subgroup of children with 22q11DS display a substantial decline in cognitive abilities starting at a young age.Objective: To determine whether early cognitive decline is associated with risk of psychotic disorder in 22q11DS.Design, Setting, And Participants: Prospective longitudinal cohort study. As part of an international research consortium initiative, we used the largest data set of intelligence (IQ) measurements in patients with 22q11DS reported to date to investigate longitudinal IQ trajectories and the risk of subsequent psychotic illness. A total of 829 patients with a confirmed hemizygous 22q11.2 deletion, recruited through 12 international clinical research sites, were included. Both psychiatric assessments and longitudinal IQ measurements were available for a subset of 411 patients (388 with≥1 assessment at age 8-24 years).Main Outcomes And Measures: Diagnosis of a psychotic disorder, initial IQ, longitudinal IQ trajectory, and timing of the last psychiatric assessment with respect to the last IQ test.Results: Among 411 patients with 22q11DS, 55 (13.4%) were diagnosed as having a psychotic disorder. The mean (SD) age at the most recent psychiatric assessment was 16.1 (6.2) years. The mean (SD) full-scale IQ at first cognitive assessment was lower in patients who developed a psychotic disorder (65.5 [12.0]) compared with those without a psychotic disorder (74.0 [14.0]). On average, children with 22q11DS showed a mild decline in IQ (full-scale IQ, 7.04 points) with increasing age, particularly in the domain of verbal IQ (9.02 points). In those who developed psychotic illness, this decline was significantly steeper (P < .001). Those with a negative deviation from the average cognitive trajectory observed in 22q11DS were at significantly increased risk for the development of a psychotic disorder (odds ratio = 2.49; 95%CI, 1.24-5.00; P = .01). The divergence of verbal IQ trajectories between those who subsequently developed a psychotic disorder and those who did not was distinguishable from age 11 years onward.Conclusions And Relevance: In 22q11DS, early cognitive decline is a robust indicator of the risk of developing a psychotic illness. These findings mirror those observed in idiopathic schizophrenia. The results provide further support for investigations of 22q11DS as a genetic model for elucidating neurobiological mechanisms underlying the development of psychosis.

Original language	English
Pages (from-to)	377-385
Number of pages	9
Journal	JAMA Psychiatry
Volume	72
DOIs	https://doi.org/10.1001/jamapsychiatry.2014.2671
Publication status	Published - 2015

Keywords

Chromosomes, Human, Pair 22 / genetics

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10.1001/jamapsychiatry.2014.2671

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Vicari, S., Vorstman, J. A. S., Breetvelt, E. J., Duijff, S. N., Eliez, S., Schneider, M., Jalbrzikowski, M., Armando, M., Shashi, V., Hooper, S. R., Chow, E. W. C., Fung, W. L. A., Butcher, N. J., Young, D. A., Mcdonald-Mcginn, D. M., Vogels, A., Van Amelsvoort, T., Gothelf, D., Weinberger, R., ... Pontillo, M. (2015). Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome. JAMA Psychiatry, 72, 377-385. https://doi.org/10.1001/jamapsychiatry.2014.2671

Vicari, Stefano ; Vorstman, Jacob A.S. ; Breetvelt, Elemi J. ; Duijff, Sasja N. ; Eliez, Stephan ; Schneider, Maude ; Jalbrzikowski, Maria ; Armando, Marco ; Shashi, Vandana ; Hooper, Stephen R. ; Chow, Eva W.C. ; Fung, Wai Lun Alan ; Butcher, Nancy J. ; Young, Donald A. ; Mcdonald-Mcginn, Donna M. ; Vogels, Annick ; Van Amelsvoort, Therese ; Gothelf, Doron ; Weinberger, Ronnie ; Weizman, Abraham ; Klaassen, Petra W.J. ; Koops, Sanne ; Kates, Wendy R. ; Antshel, Kevin M. ; Simon, Tony J. ; Ousley, Opal Y. ; Swillen, Ann ; Gur, Raquel E. ; Bearden, Carrie E. ; Kahn, René S. ; Bassett, Anne S. ; Emanuel, Beverly S. ; Zackai, Elaine H. ; Kushan, Leila ; Fremont, Wanda ; Schoch, Kelly ; Stoddard, Joel ; Cubells, Joseph ; Fu, Fiona ; Campbell, Linda E. ; Fritsch, Rosemarie ; Vergaelen, Elfi ; Neeleman, Marjolein ; Boot, Erik ; Debbané, Martin ; Philip, Nicole ; Green, Tamar ; Van Denbree, Marianne B.M. ; Murphy, Declan ; Canyelles, Jaume Morey ; Arango, Celso ; Murphy, Kieran C. ; Pontillo, Maria. / Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome. In: JAMA Psychiatry. 2015 ; Vol. 72. pp. 377-385.

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title = "Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome",

abstract = "Importance: Patients with 22q11.2 deletion syndrome (22q11DS) have an elevated (25%) risk of developing schizophrenia. Recent reports have suggested that a subgroup of children with 22q11DS display a substantial decline in cognitive abilities starting at a young age.Objective: To determine whether early cognitive decline is associated with risk of psychotic disorder in 22q11DS.Design, Setting, And Participants: Prospective longitudinal cohort study. As part of an international research consortium initiative, we used the largest data set of intelligence (IQ) measurements in patients with 22q11DS reported to date to investigate longitudinal IQ trajectories and the risk of subsequent psychotic illness. A total of 829 patients with a confirmed hemizygous 22q11.2 deletion, recruited through 12 international clinical research sites, were included. Both psychiatric assessments and longitudinal IQ measurements were available for a subset of 411 patients (388 with≥1 assessment at age 8-24 years).Main Outcomes And Measures: Diagnosis of a psychotic disorder, initial IQ, longitudinal IQ trajectory, and timing of the last psychiatric assessment with respect to the last IQ test.Results: Among 411 patients with 22q11DS, 55 (13.4%) were diagnosed as having a psychotic disorder. The mean (SD) age at the most recent psychiatric assessment was 16.1 (6.2) years. The mean (SD) full-scale IQ at first cognitive assessment was lower in patients who developed a psychotic disorder (65.5 [12.0]) compared with those without a psychotic disorder (74.0 [14.0]). On average, children with 22q11DS showed a mild decline in IQ (full-scale IQ, 7.04 points) with increasing age, particularly in the domain of verbal IQ (9.02 points). In those who developed psychotic illness, this decline was significantly steeper (P < .001). Those with a negative deviation from the average cognitive trajectory observed in 22q11DS were at significantly increased risk for the development of a psychotic disorder (odds ratio = 2.49; 95%CI, 1.24-5.00; P = .01). The divergence of verbal IQ trajectories between those who subsequently developed a psychotic disorder and those who did not was distinguishable from age 11 years onward.Conclusions And Relevance: In 22q11DS, early cognitive decline is a robust indicator of the risk of developing a psychotic illness. These findings mirror those observed in idiopathic schizophrenia. The results provide further support for investigations of 22q11DS as a genetic model for elucidating neurobiological mechanisms underlying the development of psychosis.",

keywords = "Chromosomes, Human, Pair 22 / genetics, Chromosomes, Human, Pair 22 / genetics",

author = "Stefano Vicari and Vorstman, {Jacob A.S.} and Breetvelt, {Elemi J.} and Duijff, {Sasja N.} and Stephan Eliez and Maude Schneider and Maria Jalbrzikowski and Marco Armando and Vandana Shashi and Hooper, {Stephen R.} and Chow, {Eva W.C.} and Fung, {Wai Lun Alan} and Butcher, {Nancy J.} and Young, {Donald A.} and Mcdonald-Mcginn, {Donna M.} and Annick Vogels and {Van Amelsvoort}, Therese and Doron Gothelf and Ronnie Weinberger and Abraham Weizman and Klaassen, {Petra W.J.} and Sanne Koops and Kates, {Wendy R.} and Antshel, {Kevin M.} and Simon, {Tony J.} and Ousley, {Opal Y.} and Ann Swillen and Gur, {Raquel E.} and Bearden, {Carrie E.} and Kahn, {Ren{\'e} S.} and Bassett, {Anne S.} and Emanuel, {Beverly S.} and Zackai, {Elaine H.} and Leila Kushan and Wanda Fremont and Kelly Schoch and Joel Stoddard and Joseph Cubells and Fiona Fu and Campbell, {Linda E.} and Rosemarie Fritsch and Elfi Vergaelen and Marjolein Neeleman and Erik Boot and Martin Debban{\'e} and Nicole Philip and Tamar Green and {Van Denbree}, {Marianne B.M.} and Declan Murphy and Canyelles, {Jaume Morey} and Celso Arango and Murphy, {Kieran C.} and Maria Pontillo",

year = "2015",

doi = "10.1001/jamapsychiatry.2014.2671",

language = "English",

volume = "72",

pages = "377--385",

journal = "JAMA Psychiatry",

issn = "2168-622X",

publisher = "Chicago, IL : American Medical Association, [2013]-",

}

Vicari, S, Vorstman, JAS, Breetvelt, EJ, Duijff, SN, Eliez, S, Schneider, M, Jalbrzikowski, M, Armando, M, Shashi, V, Hooper, SR, Chow, EWC, Fung, WLA, Butcher, NJ, Young, DA, Mcdonald-Mcginn, DM, Vogels, A, Van Amelsvoort, T, Gothelf, D, Weinberger, R, Weizman, A, Klaassen, PWJ, Koops, S, Kates, WR, Antshel, KM, Simon, TJ, Ousley, OY, Swillen, A, Gur, RE, Bearden, CE, Kahn, RS, Bassett, AS, Emanuel, BS, Zackai, EH, Kushan, L, Fremont, W, Schoch, K, Stoddard, J, Cubells, J, Fu, F, Campbell, LE, Fritsch, R, Vergaelen, E, Neeleman, M, Boot, E, Debbané, M, Philip, N, Green, T, Van Denbree, MBM, Murphy, D, Canyelles, JM, Arango, C, Murphy, KC & Pontillo, M 2015, 'Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome', JAMA Psychiatry, vol. 72, pp. 377-385. https://doi.org/10.1001/jamapsychiatry.2014.2671

Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome. / Vicari, Stefano; Vorstman, Jacob A.S.; Breetvelt, Elemi J.; Duijff, Sasja N.; Eliez, Stephan; Schneider, Maude; Jalbrzikowski, Maria; Armando, Marco; Shashi, Vandana; Hooper, Stephen R.; Chow, Eva W.C.; Fung, Wai Lun Alan; Butcher, Nancy J.; Young, Donald A.; Mcdonald-Mcginn, Donna M.; Vogels, Annick; Van Amelsvoort, Therese; Gothelf, Doron; Weinberger, Ronnie; Weizman, Abraham; Klaassen, Petra W.J.; Koops, Sanne; Kates, Wendy R.; Antshel, Kevin M.; Simon, Tony J.; Ousley, Opal Y.; Swillen, Ann; Gur, Raquel E.; Bearden, Carrie E.; Kahn, René S.; Bassett, Anne S.; Emanuel, Beverly S.; Zackai, Elaine H.; Kushan, Leila; Fremont, Wanda; Schoch, Kelly; Stoddard, Joel; Cubells, Joseph; Fu, Fiona; Campbell, Linda E.; Fritsch, Rosemarie; Vergaelen, Elfi; Neeleman, Marjolein; Boot, Erik; Debbané, Martin; Philip, Nicole; Green, Tamar; Van Denbree, Marianne B.M.; Murphy, Declan; Canyelles, Jaume Morey; Arango, Celso; Murphy, Kieran C.; Pontillo, Maria.

In: JAMA Psychiatry, Vol. 72, 2015, p. 377-385.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome

AU - Vicari, Stefano

AU - Vorstman, Jacob A.S.

AU - Breetvelt, Elemi J.

AU - Duijff, Sasja N.

AU - Eliez, Stephan

AU - Schneider, Maude

AU - Jalbrzikowski, Maria

AU - Armando, Marco

AU - Shashi, Vandana

AU - Hooper, Stephen R.

AU - Chow, Eva W.C.

AU - Fung, Wai Lun Alan

AU - Butcher, Nancy J.

AU - Young, Donald A.

AU - Mcdonald-Mcginn, Donna M.

AU - Vogels, Annick

AU - Van Amelsvoort, Therese

AU - Gothelf, Doron

AU - Weinberger, Ronnie

AU - Weizman, Abraham

AU - Klaassen, Petra W.J.

AU - Koops, Sanne

AU - Kates, Wendy R.

AU - Antshel, Kevin M.

AU - Simon, Tony J.

AU - Ousley, Opal Y.

AU - Swillen, Ann

AU - Gur, Raquel E.

AU - Bearden, Carrie E.

AU - Kahn, René S.

AU - Bassett, Anne S.

AU - Emanuel, Beverly S.

AU - Zackai, Elaine H.

AU - Kushan, Leila

AU - Fremont, Wanda

AU - Schoch, Kelly

AU - Stoddard, Joel

AU - Cubells, Joseph

AU - Fu, Fiona

AU - Campbell, Linda E.

AU - Fritsch, Rosemarie

AU - Vergaelen, Elfi

AU - Neeleman, Marjolein

AU - Boot, Erik

AU - Debbané, Martin

AU - Philip, Nicole

AU - Green, Tamar

AU - Van Denbree, Marianne B.M.

AU - Murphy, Declan

AU - Canyelles, Jaume Morey

AU - Arango, Celso

AU - Murphy, Kieran C.

AU - Pontillo, Maria

PY - 2015

Y1 - 2015

N2 - Importance: Patients with 22q11.2 deletion syndrome (22q11DS) have an elevated (25%) risk of developing schizophrenia. Recent reports have suggested that a subgroup of children with 22q11DS display a substantial decline in cognitive abilities starting at a young age.Objective: To determine whether early cognitive decline is associated with risk of psychotic disorder in 22q11DS.Design, Setting, And Participants: Prospective longitudinal cohort study. As part of an international research consortium initiative, we used the largest data set of intelligence (IQ) measurements in patients with 22q11DS reported to date to investigate longitudinal IQ trajectories and the risk of subsequent psychotic illness. A total of 829 patients with a confirmed hemizygous 22q11.2 deletion, recruited through 12 international clinical research sites, were included. Both psychiatric assessments and longitudinal IQ measurements were available for a subset of 411 patients (388 with≥1 assessment at age 8-24 years).Main Outcomes And Measures: Diagnosis of a psychotic disorder, initial IQ, longitudinal IQ trajectory, and timing of the last psychiatric assessment with respect to the last IQ test.Results: Among 411 patients with 22q11DS, 55 (13.4%) were diagnosed as having a psychotic disorder. The mean (SD) age at the most recent psychiatric assessment was 16.1 (6.2) years. The mean (SD) full-scale IQ at first cognitive assessment was lower in patients who developed a psychotic disorder (65.5 [12.0]) compared with those without a psychotic disorder (74.0 [14.0]). On average, children with 22q11DS showed a mild decline in IQ (full-scale IQ, 7.04 points) with increasing age, particularly in the domain of verbal IQ (9.02 points). In those who developed psychotic illness, this decline was significantly steeper (P < .001). Those with a negative deviation from the average cognitive trajectory observed in 22q11DS were at significantly increased risk for the development of a psychotic disorder (odds ratio = 2.49; 95%CI, 1.24-5.00; P = .01). The divergence of verbal IQ trajectories between those who subsequently developed a psychotic disorder and those who did not was distinguishable from age 11 years onward.Conclusions And Relevance: In 22q11DS, early cognitive decline is a robust indicator of the risk of developing a psychotic illness. These findings mirror those observed in idiopathic schizophrenia. The results provide further support for investigations of 22q11DS as a genetic model for elucidating neurobiological mechanisms underlying the development of psychosis.

AB - Importance: Patients with 22q11.2 deletion syndrome (22q11DS) have an elevated (25%) risk of developing schizophrenia. Recent reports have suggested that a subgroup of children with 22q11DS display a substantial decline in cognitive abilities starting at a young age.Objective: To determine whether early cognitive decline is associated with risk of psychotic disorder in 22q11DS.Design, Setting, And Participants: Prospective longitudinal cohort study. As part of an international research consortium initiative, we used the largest data set of intelligence (IQ) measurements in patients with 22q11DS reported to date to investigate longitudinal IQ trajectories and the risk of subsequent psychotic illness. A total of 829 patients with a confirmed hemizygous 22q11.2 deletion, recruited through 12 international clinical research sites, were included. Both psychiatric assessments and longitudinal IQ measurements were available for a subset of 411 patients (388 with≥1 assessment at age 8-24 years).Main Outcomes And Measures: Diagnosis of a psychotic disorder, initial IQ, longitudinal IQ trajectory, and timing of the last psychiatric assessment with respect to the last IQ test.Results: Among 411 patients with 22q11DS, 55 (13.4%) were diagnosed as having a psychotic disorder. The mean (SD) age at the most recent psychiatric assessment was 16.1 (6.2) years. The mean (SD) full-scale IQ at first cognitive assessment was lower in patients who developed a psychotic disorder (65.5 [12.0]) compared with those without a psychotic disorder (74.0 [14.0]). On average, children with 22q11DS showed a mild decline in IQ (full-scale IQ, 7.04 points) with increasing age, particularly in the domain of verbal IQ (9.02 points). In those who developed psychotic illness, this decline was significantly steeper (P < .001). Those with a negative deviation from the average cognitive trajectory observed in 22q11DS were at significantly increased risk for the development of a psychotic disorder (odds ratio = 2.49; 95%CI, 1.24-5.00; P = .01). The divergence of verbal IQ trajectories between those who subsequently developed a psychotic disorder and those who did not was distinguishable from age 11 years onward.Conclusions And Relevance: In 22q11DS, early cognitive decline is a robust indicator of the risk of developing a psychotic illness. These findings mirror those observed in idiopathic schizophrenia. The results provide further support for investigations of 22q11DS as a genetic model for elucidating neurobiological mechanisms underlying the development of psychosis.

KW - Chromosomes, Human, Pair 22 / genetics

UR - http://hdl.handle.net/10807/170576

U2 - 10.1001/jamapsychiatry.2014.2671

DO - 10.1001/jamapsychiatry.2014.2671

M3 - Article

VL - 72

SP - 377

EP - 385

JO - JAMA Psychiatry

JF - JAMA Psychiatry

SN - 2168-622X

ER -

Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome

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