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JAMA Psychiatry. 2015 Apr;72(4):377-85. doi: 10.1001/jamapsychiatry.2014.2671.

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

Author information

1
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
2
Office Médico-Pédagogique Research Unit, Department of Psychiatry, University of Geneva School of Medicine, Geneva, Switzerland.
3
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.
4
Child Neuropsychiatry Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, Rome, Italy.
5
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
6
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.
7
Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada10Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
8
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.
9
Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada14Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
10
Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
11
Center for Human Genetics, KU Leuven, Leuven, Belgium.
12
Department of Psychiatry and Psychology, Maastricht University, Maastricht, the Netherlands.
13
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.
14
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel20Felsenstein Medical Research Center, Petah Tikva, Israel21Geha Mental Health Center, Petah Tikva, Israel.
15
Department of Pediatric Psychology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, the Netherlands.
16
Department of Psychiatry and Behavioral Sciences, Upstate Medical University, State University of New York, Syracuse.
17
Department of Psychiatry and Behavioral Sciences, Upstate Medical University, State University of New York, Syracuse24Department of Psychology, Syracuse University, Syracuse, New York.
18
MIND (Medical Investigation of Neurodevelopmental Disorders) Institute and Department of Psychiatry and Behavioral Sciences, University of California, Davis.
19
Emory Autism Center, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
20
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

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.

Comment in

PMID:
25715178
PMCID:
PMC4383767
DOI:
10.1001/jamapsychiatry.2014.2671
[Indexed for MEDLINE]
Free PMC Article

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