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Psychiatric disorders in 22q11.2 deletion syndrome are prevalent but undertreated

Published online by Cambridge University Press:  09 September 2013

S. X. Tang ,
J. J. Yi ,
M. E. Calkins ,
D. A. Whinna ,
C. G. Kohler ,
M. C. Souders ,
D. M. McDonald-McGinn ,
E. H. Zackai ,
B. S. Emanuel  and
R. C. Gur
...Show all authors
S. X. Tang
Affiliation:
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
J. J. Yi
Affiliation:
Department of Child and Adolescent Psychiatry, Children's Hospital of Philadelphia, Philadelphia, PA, USA
M. E. Calkins
Affiliation:
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
D. A. Whinna
Affiliation:
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
C. G. Kohler
Affiliation:
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
M. C. Souders
Affiliation:
Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
D. M. McDonald-McGinn
Affiliation:
Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
E. H. Zackai
Affiliation:
Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
B. S. Emanuel
Affiliation:
Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
R. C. Gur
Affiliation:
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
R. E. Gur*
Affiliation:
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
*
* Address for correspondence: R. E. Gur, M.D., Ph.D., Neuropsychiatry Section, University of Pennsylvania, Perelman School of Medicine, 10th Floor Gates Building, Philadelphia, PA 19104, USA. (Email: [email protected])
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Abstract

Background

Chromosome 22q11.2 deletion syndrome (22q11DS) is a common genetic disorder with high rates of psychosis and other psychopathologies, but few studies discuss treatment. Our aim was to characterize the prevalence and treatment of major psychiatric illnesses in a well-characterized sample of individuals with 22q11DS.

Method

This was a cross-sectional study of 112 individuals aged 8 to 45 years with a confirmed diagnosis of 22q11DS. Each participant was administered a modified Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) and the Structured Interview for Prodromal Syndromes (SIPS). Phenotypes assessed were threshold and subthreshold psychosis, depression, mania, generalized and separation anxiety, obsessions/compulsions, inattention/hyperactivity and substance use. Histories of mental health care and current psychotropic treatment were obtained.

Results

Psychopathology was common, with 79% of individuals meeting diagnostic criteria for a disorder at the time of assessment. Diagnoses of psychosis were made in 11% of cases, attenuated positive symptom syndrome (APS) in 21%, and 47% experienced significant subthreshold symptoms. Peak occurrence of psychosis risk was during adolescence (62% of those aged 12–17 years). Criteria for a mood disorder were met by 14%, for anxiety disorder 34% and for attention deficit hyperactivity disorder (ADHD) 31%. Mental health care had been received by 63% of individuals in their lifetime, but only 40% continued therapy and 39% used psychotropics. Antipsychotics were used by 42% of participants with psychosis and none of the participants with APS. Half of those at risk for psychosis were receiving no mental health care.

Conclusions

Psychopathology is common in 22q11DS but is not adequately treated or clinically followed. Particular attention should be paid to subthreshold psychotic symptoms, especially in adolescents.

Keywords

22q11.2 deletion syndromepsychopathologypsychosistreatment
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 6 , April 2014 , pp. 1267 - 1277
Copyright
Copyright © Cambridge University Press 2013 

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References

Antshel, KM, Fremont, W, Roizen, NJ, Shprintzen, R, Higgins, AM, Dhamoon, A, Kates, WR (2006). ADHD, major depressive disorder, and simple phobias are prevalent psychiatric conditions in youth with velocardiofacial syndrome. Journal of the American Academy of Child and Adolescent Psychiatry 45, 596–603.Google Scholar
Antshel, KM, Shprintzen, R, Fremont, W, Higgins, AM, Faraone, SV, Kates, WR (2010). Cognitive and psychiatric predictors to psychosis in velocardiofacial syndrome: a 3-year follow-up study. Journal of the American Academy of Child and Adolescent Psychiatry 49, 333–344.Google Scholar
Bassett, AS, Chow, EW (2008). Schizophrenia and 22q11.2 deletion syndrome. Current Psychiatry Reports 10, 148–157.Google Scholar
Bassett, AS, Chow, EW, AbdelMalik, P, Gheorghiu, M, Husted, J, Weksberg, R (2003). The schizophrenia phenotype in 22q11 deletion syndrome. American Journal of Psychiatry 160, 1580–1586.Google Scholar
Bassett, AS, McDonald-McGinn, DM, Devriendt, K, Digilio, MC, Goldenberg, P, Habel, A, Marino, B, Oskarsdottir, S, Philip, N, Sullivan, K, Swillen, A, Vorstman, J; International 22q11.2 Deletion Syndrome Consortium (2011). Practical guidelines for managing patients with 22q11.2 deletion syndrome. Journal of Pediatrics 159, 332–9.e1.Google Scholar
Botto, LD, May, K, Fernhoff, PM, Correa, A, Coleman, K, Rasmussen, SA, Merritt, RK, O'Leary, LA, Wong, L-Y, Elixson, EM (2003). A population-based study of the 22q11. 2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics 112, 101–107.Google Scholar
Dreessen, L, Arntz, A (1998). Short-interval test-retest interrater reliability of the Structured Clinical Interview for DSM-III-R personality disorders (SCID-II) in outpatients. Journal of Personality Disorders 12, 138–148.Google Scholar
Fabbro, A, Rizzi, E, Schneider, M, Debbane, M, Eliez, S (2012). Depression and anxiety disorders in children and adolescents with velo-cardio-facial syndrome (VCFS). European Child and Adolescent Psychiatry 21, 379–385.Google Scholar
First, MB, Gibbon, M (2004). The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II). In Comprehensive Handbook of Psychological Assessment. Vol. 2, Personality Assessment (ed. Hilsenroth, M. J. and Segal, D. L.), pp. 134–143. John Wiley & Sons, Inc.: Hoboken, NJ.Google Scholar
Goldenberg, PC, Calkins, ME, Richard, J, McDonald-McGinn, D, Zackai, E, Mitra, N, Emanuel, B, Devoto, M, Borgmann-Winter, K, Kohler, C, Conroy, CG, Gur, RC, Gur, RE (2012). Computerized neurocognitive profile in young people with 22q11.2 deletion syndrome compared to youths with schizophrenia and at-risk for psychosis. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 159B, 87–93.Google Scholar
Gothelf, D, Feinstein, C, Thompson, T, Gu, E, Penniman, L, Van Stone, E, Kwon, H, Eliez, S, Reiss, AL (2007). Risk factors for the emergence of psychotic disorders in adolescents with 22q11.2 deletion syndrome. American Journal of Psychiatry 164, 663–669.Google Scholar
Green, T, Gothelf, D, Glaser, B, Debbane, M, Frisch, A, Kotler, M, Weizman, A, Eliez, S (2009). Psychiatric disorders and intellectual functioning throughout development in velocardiofacial (22q11.2 deletion) syndrome. Journal of the American Academy of Child and Adolescent Psychiatry 48, 1060–1068.Google Scholar
Gur, RE, Kohler, C, Turetsky, BI, Siegel, SJ, Kanes, SJ, Bilker, WB, Brennan, AR, Gur, RC (2004). A sexually dimorphic ratio of orbitofrontal to amygdala volume is altered in schizophrenia. Biological Psychiatry 55, 512–517.Google Scholar
Hafner, H, an der Heiden, W, Behrens, S, Gattaz, WF, Hambrecht, M, Loffler, W, Maurer, K, Munk-Jorgensen, P, Nowotny, B, Riecher-Rossler, A, Stein, A (1998). Causes and consequences of the gender difference in age at onset of schizophrenia. Schizophrenia Bulletin 24, 99–113.Google Scholar
Jawad, AF, McDonald-McGinn, DM, Zackai, E, Sullivan, KE (2001). Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Journal of Pediatrics 139, 715–723.Google Scholar
Jolin, EM, Weller, RA, Jessani, NR, Zackai, EH, McDonald-McGinn, DM, Weller, EB (2009). Affective disorders and other psychiatric diagnoses in children and adolescents with 22q11.2 deletion syndrome. Journal of Affective Disorders 119, 177–180.Google Scholar
Jolin, EM, Weller, RA, Weller, EB (2012). Occurrence of affective disorders compared to other psychiatric disorders in children and adolescents with 22q11.2 deletion syndrome. Journal of Affective Disorders 136, 222–228.Google Scholar
Kaufman, J, Birmaher, B, Brent, D, Rao, U, Flynn, C, Moreci, P, Williamson, D, Ryan, N (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children – Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child and Adolescent Psychiatry 36, 980–988.Google Scholar
McDonald-McGinn, DM, Minugh-Purvis, N, Kirschner, RE, Jawad, A, Tonnesen, MK, Catanzaro, JR, Goldmuntz, E, Driscoll, D, Larossa, D, Emanuel, BS, Zackai, EH (2005). The 22q11.2 deletion in African-American patients: an underdiagnosed population? American Journal of Medical Genetics . Part A 134, 242–246.Google Scholar
McDonald-McGinn, DM, Tonnesen, MK, Laufer-Cahana, A, Finucane, B, Driscoll, DA, Emanuel, BS, Zackai, EH (2001). Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net! Genetics in Medicine 3, 23–29.Google Scholar
Merikangas, KR, He, J-P, Rapoport, J, Vitiello, B, Olfson, M (2013). Medication use in US youth with mental disorders. JAMA Pediatrics 167, 141–148.Google Scholar
Merikangas, KR, He, MJ-P, Burstein, M, Swanson, MSA, Avenevoli, S, Cui, ML, Benjet, C, Georgiades, K, Swendsen, J (2010). Lifetime prevalence of mental disorders in US adolescents: results from the National Comorbidity Study – Adolescent Supplement (NCS-A). Journal of the American Academy of Child and Adolescent Psychiatry 49, 980–989.Google Scholar
Michaelovsky, E, Frisch, A, Carmel, M, Patya, M, Zarchi, O, Green, T, Basel-Vanagaite, L, Weizman, A, Gothelf, D (2012). Genotype-phenotype correlation in 22q11.2 deletion syndrome. BMC Medical Genetics 13, 122.Google Scholar
Miller, TJ, McGlashan, TH, Rosen, JL, Cadenhead, K, Cannon, T, Ventura, J, McFarlane, W, Perkins, DO, Pearlson, GD, Woods, SW (2003). Prodromal assessment with the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms: predictive validity, interrater reliability, and training to reliability. Schizophrenia Bulletin 29, 703–715.Google Scholar
Murphy, KC, Jones, LA, Owen, MJ (1999). High rates of schizophrenia in adults with velo-cardio-facial syndrome. Archives of General Psychiatry 56, 940–945.Google Scholar
Niklasson, L, Rasmussen, P, Oskarsdóttir, S, Gillberg, C (2009). Autism, ADHD, mental retardation and behavior problems in 100 individuals with 22q11 deletion syndrome. Research in Developmental Disabilities 30, 763–773.Google Scholar
Schreiner, MJ, Lazaro, MT, Jalbrzikowski, M, Bearden, CE (2013). Converging levels of analysis on a genomic hotspot for psychosis: insights from 22q11.2 deletion syndrome. Neuropharmacology 68, 157–173.Google Scholar
Shapiro, DI, Cubells, JF, Ousley, OY, Rockers, K, Walker, EF (2011). Prodromal symptoms in adolescents with 22q11.2 deletion syndrome and schizotypal personality disorder. Schizophrenia Research 129, 20–28.Google Scholar
Stoddard, J, Niendam, T, Hendren, R, Carter, C, Simon, TJ (2010). Attenuated positive symptoms of psychosis in adolescents with chromosome 22q11.2 deletion syndrome. Schizophrenia Research 118, 118–121.Google Scholar
Veerapandiyan, A, Abdul-Rahman, OA, Adam, MP, Lyons, MJ, Manning, M, Coleman, K, Kobrynski, L, Taneja, D, Schoch, K, Zimmerman, HH, Shashi, V (2011). Chromosome 22q11.2 deletion syndrome in African-American patients: a diagnostic challenge. American Journal of Medical Genetics. Part A 155A, 2186–2195.Google Scholar
Vorstman, JA, Morcus, ME, Duijff, SN, Klaassen, PW, Heineman-de Boer, JA, Beemer, FA, Swaab, H, Kahn, RS, van Engeland, H (2006). The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. Journal of the American Academy of Child and Adolescent Psychiatry 45, 1104–1113.Google Scholar
Wapner, RJ, Martin, CL, Levy, B, Ballif, BC, Eng, CM, Zachary, JM, Savage, M, Platt, LD, Saltzman, D, Grobman, WA, Klugman, S, Scholl, T, Simpson, JL, McCall, K, Aggarwal, VS, Bunke, B, Nahum, O, Patel, A, Lamb, AN, Thom, EA, Beaudet, AL, Ledbetter, DH, Shaffer, LG, Jackson, L (2012). Chromosomal microarray versus karyotyping for prenatal diagnosis. New England Journal of Medicine 367, 2175–2184.Google Scholar
Wilkinson, GS, Robertson, GJ (2006). Wide Range Achievement Test, Fourth Edition (WRAT4). Psychological Assessment Resources: Lutz, FL.Google Scholar