1. [In Process Citation]
- Author
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Vorstman, Jacob A S, Breetvelt, Elemi J., Duijff, Sasja N., Eliez, Stephan, Schneider, Maude, Jalbrzikowski, Maria, Armando, Marco, Vicari, Stefano, 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, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), and RS: MHeNs - R2 - Mental Health
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Male ,Chromosomes, Human, Pair 22 ,Neuropsychological Tests ,Pair 22 / genetics ,ddc:616.89 ,0302 clinical medicine ,Risk Factors ,Psychology ,Prospective Studies ,Cognitive decline ,Child ,Prospective cohort study ,Pediatric ,Intelligence Tests ,Intelligence quotient ,Psychiatric assessment ,Age Factors ,Serious Mental Illness ,3. Good health ,Psychiatry and Mental health ,Mental Health ,Schizophrenia ,Cognitive Sciences ,Female ,Human ,Clinical psychology ,Psychosis ,Adolescent ,International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome ,Chromosomes ,Article ,Young Adult ,03 medical and health sciences ,Settore MED/39 - NEUROPSICHIATRIA INFANTILE ,Arts and Humanities (miscellaneous) ,Clinical Research ,Genetic model ,medicine ,DiGeorge Syndrome ,Dementia ,Humans ,Other Medical and Health Sciences ,Prevention ,medicine.disease ,Brain Disorders ,030227 psychiatry ,Chromosomes, Human, Pair 22 / genetics ,Psychotic Disorders ,Pair 22 ,Cognition Disorders ,030217 neurology & neurosurgery - Abstract
© 2015 American Medical Association. All rights reserved. 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.
- Published
- 2015