Cognitive Decline Preceding the Onset of Psychosis in Patients With 22q11.2 Deletion Syndrome

• Type of Material: Article
• Authors: Jacob A.S. Vorstman, University Medical Center Utrecht; Elemi J. Breetvelt, University Medical Center Utrecht; Sasja N. Duijff, University Medical Center Utrecht; Stephen Eliez, University of Geneva; Maude Schneider, University of Geneva; Maria Jalbrzikowski, University of California Los Angeles; Marco Armando, Bambino Gesù Children’s Hospital; Stefano Vicari, Bambino Gesù Children’s Hospital; Vandana Shashi, Duke University; Stephen R. Hooper, University of North Carolina; Eva W.C. Chow, Center for Addiction and Mental Health; Wai Lun Alan Fung, Center for Addiction and Mental Health; Nancy J. Butcher, Center for Addiction and Mental Health; Donald A. Young, Center for Addiction and Mental Health; Donna M. McDonald-McGinn, Childrens Hospital of Philadelphia; Annick Vogels, Katholieke University Leuven; Therese van Amelsvoort, Maastricht University; Doron Gothelf, Edmond & Lily Safra Children's Hospital; Ronnie Weinberger, Edmond & Lily Safra Children's Hospital; Abraham Weizman, Tel Aviv University; Petra WJ Klaassen, University Medical Center Utrecht; Sanne Koops, University Medical Center Utrecht; Wendy R. Kates, State University of New York at Upstate Medical University; Kevin M. Antshel, State University of New York at Upstate Medical University; Tony J. Simon, University of California Davis; Opal Ousley, Emory University; Ann Swillen, Katholieke University Leuven; Raquel E. Gur, University of Pennsylvania; Carrie E. Bearden, University of California Los Angeles; René S. Kahn, University Medical Center Utrecht; Anne S. Bassett, Center for Addiction and Mental Health
• Language: English
• Date: 2015-04-01
• Publisher: American Medical Association (AMA)
• Publication Version: Final Published Version
• Copyright Statement: © 2015 American Medical Association. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1001/jamapsychiatry.2014.2671
• Title of Journal or Parent Work: JAMA Psychiatry
• ISSN: 2168-622X
• Volume: 72
• Issue: 4
• Start Page: 377
• End Page: 385
• Grant/Funding Information: See publication for full funding statement.
• Keywords: Psychiatry; GROWTH CHARTS; PREMORBID IQ; ADULT SCHIZOPHRENIA; Science & Technology; PSYCHIATRIC-DISORDERS; CHILDHOOD; PROSPECTIVE COHORT; CHILDREN; INTELLECTUAL DECLINE; CARDIO-FACIAL SYNDROME; Life Sciences & Biomedicine; RISK
• Research Categories: Psychology, Behavioral

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.