title: Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Jacob A S
authors.initials: JA
authors.lastname: Vorstman
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Elemi J
authors.initials: EJ
authors.lastname: Breetvelt
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Sasja N
authors.initials: SN
authors.lastname: Duijff
authors.affiliation: Office Médico-Pédagogique Research Unit, Department of Psychiatry, University of Geneva School of Medicine, Geneva, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Eliez
authors.affiliation: Office Médico-Pédagogique Research Unit, Department of Psychiatry, University of Geneva School of Medicine, Geneva, Switzerland.
authors.forename: Maude
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles4Department of Psychology, University of California, Los Angeles.
authors.forename: Maria
authors.initials: M
authors.lastname: Jalbrzikowski
authors.affiliation: Child Neuropsychiatry Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Armando
authors.affiliation: Child Neuropsychiatry Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vicari
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Vandana
authors.initials: V
authors.lastname: Shashi
authors.affiliation: Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill8Department of Allied Health Sciences, University of North Carolina School of Medicine, Chapel Hill.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Hooper
authors.affiliation: Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada10Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Eva W C
authors.initials: EW
authors.lastname: Chow
authors.affiliation: Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada10Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada11Dalglish Family Hearts and Minds Clinic for Adults With 22q11.2 Deletion Syndr.
authors.forename: Wai Lun Alan
authors.initials: WL
authors.lastname: Fung
authors.affiliation: Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada14Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Butcher
authors.affiliation: Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada10Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Young
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Donna M
authors.initials: DM
authors.lastname: McDonald-McGinn
authors.affiliation: Center for Human Genetics, KU Leuven, Leuven, Belgium.
authors.forename: Annick
authors.initials: A
authors.lastname: Vogels
authors.affiliation: Department of Psychiatry and Psychology, Maastricht University, Maastricht, the Netherlands.
authors.forename: Therese
authors.initials: T
authors.lastname: van Amelsvoort
authors.affiliation: Behavioral Neurogenetics Center, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel19Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Gothelf
authors.affiliation: Behavioral Neurogenetics Center, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel19Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Weinberger
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel20Felsenstein Medical Research Center, Petah Tikva, Israel21Geha Mental Health Center, Petah Tikva, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
authors.affiliation: Department of Pediatric Psychology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, the Netherlands.
authors.forename: Petra W J
authors.initials: PW
authors.lastname: Klaassen
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: Koops
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Upstate Medical University, State University of New York, Syracuse.
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Kates
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Upstate Medical University, State University of New York, Syracuse24Department of Psychology, Syracuse University, Syracuse, New York.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Antshel
authors.affiliation: MIND (Medical Investigation of Neurodevelopmental Disorders) Institute and Department of Psychiatry and Behavioral Sciences, University of California, Davis.
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Simon
authors.affiliation: Emory Autism Center, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Opal Y
authors.initials: OY
authors.lastname: Ousley
authors.affiliation: Center for Human Genetics, KU Leuven, Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Swillen
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Gur
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles4Department of Psychology, University of California, Los Angeles.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Bearden
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.affiliation: Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada10Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada11Dalglish Family Hearts and Minds Clinic for Adults With 22q11.2 Deletion Syndr.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Bassett
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D003072:Cognition Disorders / Q000150:complications / Q000523:psychology*; D004062:DiGeorge Syndrome / Q000150:complications / Q000523:psychology*; D005260:Female; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000150:complications / Q000523:psychology*; D012307:Risk Factors; D055815:Young Adult