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Psychiatric Disorders From Childhood to Adulthood in 22q11.2 Deletion Syndrome: Results From the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome
Maude Schneider, M.Sc.; Martin Debbané, Ph.D.; Anne S. Bassett, M.D., F.R.C.P.C.; Eva W.C. Chow, M.D., F.R.C.P.C.; Wai Lun Alan Fung, M.D., Sc.D.; Marianne B.M. van den Bree, Ph.D.; Michael Owen, M.D., Ph.D.; Kieran C. Murphy, M.D., Ph.D.; Maria Niarchou, Ph.D.; Wendy R. Kates, Ph.D.; Kevin M. Antshel, Ph.D.; Wanda Fremont, M.D.; Donna M. McDonald-McGinn, M.S., C.G.C.; Raquel E. Gur, M.D., Ph.D.; Elaine H. Zackai, M.D.; Jacob Vorstman, M.D., Ph.D.; Sasja N. Duijff, Ph.D.; Petra W.J. Klaassen, M.Sc.; Ann Swillen, Ph.D.; Doron Gothelf, M.D.; Tamar Green, M.D.; Abraham Weizman, M.D.; Therese Van Amelsvoort, M.D., Ph.D.; Laurens Evers, M.D.; Erik Boot, M.D., Ph.D.; Vandana Shashi, M.D.; Stephen R. Hooper, Ph.D.; Carrie E. Bearden, Ph.D.; Maria Jalbrzikowski, Ph.D.; Marco Armando, M.D., Ph.D.; Stefano Vicari, M.D.; Declan G. Murphy, M.D.; Opal Ousley, Ph.D.; Linda E. Campbell, Ph.D.; Tony J. Simon, Ph.D.; Stephan Eliez, M.D.; for the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome
Am J Psychiatry 2014;171:627-639. doi:10.1176/appi.ajp.2013.13070864
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Dr. Ousley is a collaborator in a Biomarin Pharmaceutical study. The other authors report no financial relationships with commercial interests.

Supported by funding from the NIMH International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome; the Swiss National Fund to Dr. Eliez (grants PP00B_102864 and 32473B_121996); from the National Center of Competence in Research program Synapsy, financed by the Swiss National Science Foundation, to Dr. Eliez (grant 51AU40_125759); from the Canadian Institutes of Health Research to Drs. Bassett and Chow (grants MOP-97800, MOP-89066, and MOP-74631); from the Ontario Mental Health Foundation to Dr. Chow; from support of Dr. Bassett as the Canada Research Chair in Schizophrenia Genetics and Genomic Disorders and as the Dalglish Chair in 22q11.2 Deletion Syndrome; from the Baily Thomas Charitable Trust to Drs. van den Bree and Owen (grant 2315/1); from the Waterloo Foundation to Drs. van den Bree and Owen (grant 912-1234); from the Wellcome Trust Institutional Strategic Support Fund to Drs. van den Bree and Owen; from the Wellcome Trust to Dr. K.C. Murphy and Dr. Owen (grant GR067869MF); from Ireland’s Health Research Board to Dr. K.C. Murphy (grants RP/2004/30 and RP/2008/169); from the Health Foundation to Drs. K.C. Murphy and D.G. Murphy (grant 1206/188); from NIMH to Dr. Kates (grant MH-064824), Dr. Gur (grant MH-087626), Drs. McDonald-McGinn and Zackai (grant MH-087636), Dr. Shashi (grants MH-78015 and MH-091314), and Dr. Bearden (grant RO1 MH-085953); from the National Institute of Child Health and Human Development to Drs. McDonald-McGinn and Zackai (grant HD-070454), Dr. Bearden (P50 HD-055784 [CART pilot project grant]), and Dr. Simon (grant R01 HD-042974); from the Brain and Behavior Research Foundation (formerly NARSAD) to Dr. Vorstman (Young Investigator Award), Dr. Van Amelsvoort (Young Investigator Award), Dr. Armando (Young Investigator Award), and Dr. Ousley; from the State University of New York Hendricks Fund to Dr. Antshel; from the Basil O’Connor Starter Scholar Research Award by the March of Dimes to Dr. Gothelf (grant 5-FY06-590); from the Binational Science Foundation to Dr. Gothelf (grant 2011378); from the Gazit-Globe Award to Dr. Green; from the Dutch Brain Foundation to Dr. Van Amelsvoort; from the Robert W. Woodruff Fund to Dr. Ousley; from the Simons Foundation to Dr. Ousley; from a Hunter Medical Research Institute Post-Doctoral Fellowship to Dr. Campbell; and from an Australian Training Fellowship awarded by the National Health and Medical Research Council of Australia to Dr. Simon (grant 455614).

From the Office Médico-Pédagogique Research Unit, Department of Psychiatry, University of Geneva School of Medicine, Geneva; the Clinical Genetics Research Program and Clinical Genetics Service, Centre for Addiction and Mental Health, Toronto; the Dalglish Family Hearts and Minds Clinic for 22q11.2 Deletion Syndrome, University Health Network, Toronto; the Department of Psychiatry, University of Toronto; the Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, U.K.; the Department of Psychiatry, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin; the Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, N.Y.; the Department of Psychology, Syracuse University, Syracuse, N.Y.; the Division of Human Genetics, Children’s Hospital of Philadelphia; the Departments of Pediatrics and Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center, Utrecht, the Netherlands; the Department of Pediatric Psychology, Wilhelmina Children’s Hospital, University Medical Center, Utrecht, the Netherlands; the Centre for Human Genetics, University Hospital Gasthuisberg, and the Department of Human Genetics, University of Leuven, Leuven, Belgium; the Behavioral Neurogenetics Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Geha Mental Health Center and Felsenstein Medical Research Center, Sackler Faculty of Medicine, Petah Tiqwa, Israel; the Department of Psychiatry and Psychology, Maastricht University, Maastricht, the Netherlands; the Koraalgroup, Heel, the Netherlands; Ipse de Bruggen, Centre for People with Intellectual Disability, Zwammerdam, the Netherlands; the Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, N.C.; the Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, N.C.; the Semel Institute for Neuroscience and Human Behavior and the Department of Psychology, University of California, Los Angeles; the Child Neuropsychiatry Unit, Department of Neuroscience, Bambino Gesù Children’s Hospital, Rome; the Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, King's College London; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta; the School of Psychology, University of Newcastle, Newcastle, Australia; the MIND Institute and Department of Psychiatry, University of California, Davis.

Address correspondence to Ms. Schneider (maude.schneider@unige.ch).

Copyright © 2014 by the American Psychiatric Association

Received July 05, 2013; Revised November 04, 2013; Accepted December 19, 2013.

Abstract

Objective  Chromosome 22q11.2 deletion syndrome is a neurogenetic disorder associated with high rates of schizophrenia and other psychiatric conditions. The authors report what is to their knowledge the first large-scale collaborative study of rates and sex distributions of psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome. The associations among psychopathology, intellect, and functioning were examined in a subgroup of participants.

Method  The 1,402 participants with 22q11.2 deletion syndrome, ages 6–68 years, were assessed for psychiatric disorders with validated diagnostic instruments. Data on intelligence and adaptive functioning were available for 183 participants ages 6 to 24 years.

Results  Attention deficit hyperactivity disorder (ADHD) was the most frequent disorder in children (37.10%) and was overrepresented in males. Anxiety disorders were more prevalent than mood disorders at all ages, but especially in children and adolescents. Anxiety and unipolar mood disorders were overrepresented in females. Psychotic disorders were present in 41% of adults over age 25. Males did not predominate in psychotic or autism spectrum disorders. Hierarchical regressions in the subgroup revealed that daily living skills were predicted by the presence of anxiety disorders. Psychopathology was not associated with communication or socialization skills.

Conclusions  To the authors’ knowledge, this is the largest study of psychiatric morbidity in 22q11.2 deletion syndrome. It validates previous findings that this condition is one of the strongest risk factors for psychosis. Anxiety and developmental disorders were also prevalent. These results highlight the need to monitor and reduce the long-term burden of psychopathology in 22q11.2 deletion syndrome.

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FIGURE 1. Age Distribution of 1,402 Participants With 22q11.2 Deletion Syndrome Assessed for Psychiatric Disorders

FIGURE 2. Prevalence of Schizophrenia Spectrum Disorders and Distribution of Specific Disorders by Age in Participants With 22q11.2 Deletion Syndromea

a Among the 235 subjects with schizophrenia spectrum disorders, the prevalence of a schizophrenia diagnosis increased significantly over the age groups (χ2=12.54, df=4, p=0.01), whereas the diagnosis of psychotic disorder not otherwise specified decreased (χ2=17.17, df=4, p=0.002).

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TABLE 1.Number of Participants in a Study of Psychiatric Disorders at Each Site in the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome
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a CAPA, Child and Adolescent Psychiatric Assessment (30); SCAN, Schedules for Clinical Assessment in Neuropsychiatry (31); SCID, Structured Clinical Interview for DSM-IV Axis I Disorders (32); ADOS, Autism Diagnostic Observation Schedule (33); K-SADS, Schedule for Affective Disorders and Schizophrenia for School-Age Children (34); ADI-R, Autism Diagnostic Interview–Revised (35); DICA, Diagnostic Interview for Children and Adolescents (36); MINI, Mini International Neuropsychiatric Interview (37); Mini PAS-ADD, Mini Psychiatric Assessment Schedules for Adults With Developmental Disabilities (38); CDISC, Computerized Diagnostic Interview Schedule for Children (39).

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TABLE 2.Prevalence of DSM-IV-TR Psychiatric Disorders in Five Age Groups of Subjects With 22q11.2 Deletion Syndrome
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a Significant increase with age (χ2=214.70, df=4, p<0.001).

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b Significant decrease with age (χ2=15.49, df=4, p=0.004).

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c Significant decrease with age (χ2=13.67, df=4, p=0.008).

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d Significant decrease with age (χ2=57.13, df=4, p<0.001).

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e Significant decrease with age (χ2=24.57, df=4, p<0.001).

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f Significant increase with age (χ2=47.35, df=4, p<0.001).

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g Significant increase with age (χ2=37.88, df=4, p<0.001).

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h Significant difference across age groups (χ2=14.66, df=4, p=0.05).

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i Significant difference between children and adolescents (χ2=13.19, df=1, p<0.001) and between adolescents and adults (χ2=4.59, df=1, p=0.04).

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j Significant difference across age groups (χ2=10.07, df=2, p=0.007).

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k Nonsignificant difference across age groups (χ2=5.06, df=2, p=0.08).

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TABLE 3.Effects of Age, Intellectual Functioning, and Psychiatric Diagnoses on Functional Domains in 183 Individuals Ages 6–24 With 22q11.2 Deletion Syndrome
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a Significant effect.

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b Nearly significant effect.

+

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