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

International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome, Joel Stoddard

Research output: Contribution to journalArticle

85 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)377-385
Number of pages9
JournalJAMA Psychiatry
Volume72
Issue number4
DOIs
StatePublished - Apr 1 2015

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DiGeorge Syndrome
Psychotic Disorders
Psychiatry
Schizophrenia
Cognitive Dysfunction
Onset
Syndrome
Psychosis
Aptitude
Genetic Models
Intelligence
Research
Longitudinal Studies
Cohort Studies
Odds Ratio
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health

Cite this

International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome, & Stoddard, J. (2015). Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome. JAMA Psychiatry, 72(4), 377-385. https://doi.org/10.1001/jamapsychiatry.2014.2671

Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome. / International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome; Stoddard, Joel.

In: JAMA Psychiatry, Vol. 72, No. 4, 01.04.2015, p. 377-385.

Research output: Contribution to journalArticle

International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome & Stoddard, J 2015, 'Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome', JAMA Psychiatry, vol. 72, no. 4, pp. 377-385. https://doi.org/10.1001/jamapsychiatry.2014.2671
International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome, Stoddard J. Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome. JAMA Psychiatry. 2015 Apr 1;72(4):377-385. https://doi.org/10.1001/jamapsychiatry.2014.2671
International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome ; Stoddard, Joel. / Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome. In: JAMA Psychiatry. 2015 ; Vol. 72, No. 4. pp. 377-385.
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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.",
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T1 - Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome

AU - International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome

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 - Vicari, Stefano

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 - Stoddard, Joel

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

PY - 2015/4/1

Y1 - 2015/4/1

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.

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