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Trajectories of psychiatric diagnoses and medication usage in youth with 22q11.2 deletion syndrome: a 9-year longitudinal study

Published online by Cambridge University Press:  18 September 2018

Wendy R. Kates ,
Margaret A. Mariano ,
Kevin M. Antshel ,
Shanel Chandra ,
Hilary Gamble ,
Mark Giordano ,
Eric MacMaster ,
Mirabelle Mattar ,
Diane St. Fleur  and
Stephen V. Faraone
...Show all authors
Wendy R. Kates*
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, New York, USA
Margaret A. Mariano
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, New York, USA
Kevin M. Antshel
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, New York, USA Department of Psychology, Syracuse University, Syracuse, New York, USA
Shanel Chandra
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, New York, USA
Hilary Gamble
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, New York, USA
Mark Giordano
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, New York, USA
Eric MacMaster
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, New York, USA
Mirabelle Mattar
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, New York, USA
Diane St. Fleur
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, New York, USA
Stephen V. Faraone
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, New York, USA
Wanda P. Fremont
Affiliation:
Departments of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, New York, USA
*
Author for correspondence: Wendy R. Kates, E-mail: katesw@upstate.edu
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Abstract

Background

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with high rates of psychiatric disorders, including schizophrenia in up to 30% of individuals with the syndrome. Despite this, we know relatively little about trajectories and predictors of persistence of psychiatric disorders from middle childhood to early adulthood. Accordingly, we followed youth over four timepoints, every 3 years, to assess long-term trajectories of attention-deficit hyperactivity disorder (ADHD), anxiety, mood, and psychosis-spectrum disorders (PSDs), as well as medication usage.

Methods

Eighty-seven youth with 22q11DS and 65 controls between the ages of 9 and 15 years at the first timepoint (T1; mean age 11.88 ± 2.1) were followed for 9 years (mean age of 21.22 ± 2.01 years at T4). Baseline cognitive, clinical, and familial predictors of persistence were identified for each class of psychiatric disorders.

Results

Baseline age and parent-rated hyperactivity scores predicted ADHD persistence [area under curve (AUC) = 0.81]. The presence of family conflict predicted persistence of anxiety disorders (ADs) whereas parent ratings of child internalizing symptoms predicted persistence of both anxiety and mood disorders (MDs) (AUC = 0.84 and 0.83, respectively). Baseline prodromal symptoms predicted persistent and emergent PSDs (AUC = 0.83). Parent-reported use of anti-depressants/anxiolytics increased significantly from T1 to T4.

Conclusions

Psychiatric, behavioral, and cognitive functioning during late childhood and early adolescence successfully predicted children with 22q11DS who were at highest risk for persistent psychiatric illness in young adulthood. These findings emphasize the critical importance of early assessments and interventions in youth with 22q11DS.

Keywords

22q11.2 deletion syndromeDiGeorge syndromelongitudinal trajectoriesmedication usagepsychiatric diagnosticpersistencepsychosis-spectrum disorderschizophreniavelo-cardio-facial syndrome

Information

Type
Original Articles
Information
Psychological Medicine , Volume 49 , Issue 11 , August 2019 , pp. 1914 - 1922
Copyright
Copyright © Cambridge University Press 2018 

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References

AACAP Work Group on Quality Issues, Birmaher, B, Brent, D, Bernet, W, Bukstein, O, Walter, H, Benson, RS, Chrisman, A, Farchione, T, Greenhill, L, Hamilton, J, Keable, H, Kinlan, J, Schoettle, U, Stock, S, Ptakowski, KK and Medicus, J (2007 a) Practice parameter for the assessment and treatment of children and adolescents with depressive disorders. Journal of the American Academy of Child and Adolescent Psychiatry 46, 1503–1526.Google Scholar
AACAP Work Group on Quality Issues, McClellan, J, Kowatch, R and Findling, RL (2007 b) Practice parameter for the assessment and treatment of children and adolescents with bipolar disorder. Journal of the American Academy of Child and Adolescent Psychiatry 46, 107–125.Google Scholar
AACAP Work Group on Quality Issues and Pliszka, S (2007 c). Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry 46, 894–921.Google Scholar
American Academy of Child and Adolescent Psychiatry (AACAP) Committee on Quality Issues (CQI), McClellan, J and Stock, S (2013) Practice parameter for the assessment and treatment of children and adolescents with schizophrenia. Journal of the American Academy of Child and Adolescent Psychiatry 52, 976–990.Google Scholar
Antshel, KM, Fremont, W, Roizen, NJ, Shprintzen, R, Higgins, AM, Dhamoon, A and 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, Faraone, SV, Fremont, W, Monuteaux, MC, Kates, WR, Doyle, A, Mick, E and Biederman, J (2007) Comparing ADHD in velocardiofacial syndrome to idiopathic ADHD: a preliminary study. Journal of Attention Disorders 11, 64–73.Google Scholar
Antshel, KM, Shprintzen, R, Fremont, W, Higgins, AM, Faraone, SV and 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
Antshel, KM, Hendricks, K, Shprintzen, R, Fremont, W, Higgins, AM, Faraone, SV and Kates, WR (2013) The longitudinal course of attention deficit/hyperactivity disorder in velo-cardio-facial syndrome. The Journal of Pediatrics 163, 187–193, e1.Google Scholar
Asselmann, E and Beesdo-Baum, K (2015) Predictors of the course of anxiety disorders in adolescents and young adults. Current Psychiatry Reports 17, 7.Google Scholar
Bassett, AS and Chow, EW (2008) Schizophrenia and 22q11. 2 deletion syndrome. Current Psychiatry Reports 10, 148.Google Scholar
Biederman, J, Petty, CR, Clarke, A, Lomedico, A and Faraone, SV (2011) Predictors of persistent ADHD: an 11-year follow-up study. Journal of Psychiatric Research 45, 150–155.Google Scholar
Biederman, J, Petty, CR, O'Connor, KB, Hyder, LL and Faraone, SV (2012) Predictors of persistence in girls with attention deficit hyperactivity disorder: results from an 11-year controlled follow-up study. Acta Psychiatrica Scandinavica 125, 147–156.Google Scholar
Boot, E, Butcher, N, Vorstman, J, van Amelsvoort, T, Fung, W and Bassett, A (2015) Pharmacological treatment of 22q11.2 deletion syndrome-related psychoses. Pharmacopsychiatry 25, 219–220.Google Scholar
Botto, LD, May, K, Fernhoff, PM, Correa, A, Coleman, K, Rasmussen, SA, Merritt, RK, O'Leary, LA, Wong, LY, Elixson, EM, Mahle, WT and Campbell, RM (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
Bruce, SE, Yonkers, KA, Otto, MW, Eisen, JL, Weisberg, RB, Pagano, M, Shea, MT and Keller, MB (2005) Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study. American Journal of Psychiatry 162, 1179–1187.Google Scholar
Butcher, NJ, Fung, WL, Fitzpatrick, L, Guna, A, Andrade, DM, Lang, AE, Chow, EW and Bassett, AS (2015) Response to clozapine in a clinically identifiable subtype of schizophrenia. The British Journal of Psychiatry: the Journal of Mental Science 206, 484–491.Google Scholar
Cherkasova, M, Sulla, EM, Dalena, KL, Ponde, MP and Hechtman, L (2013) Developmental course of attention deficit hyperactivity disorder and its predictors. Journal of the Canadian Academy of Child and Adolescent Psychiatry 22, 47–54.Google Scholar
Copeland, WE, Shanahan, L, Costello, EJ and Angold, A (2009) Childhood and adolescent psychiatric disorders as predictors of young adult disorders. Archives of General Psychiatry 66, 764–772.Google Scholar
Copeland, WE, Angold, A, Shanahan, L and Costello, EJ (2014) Longitudinal patterns of anxiety from childhood to adulthood: the great smoky mountains study. Journal of the American Academy of Child and Adolescent Psychiatry 53, 21–33.Google Scholar
Dekker, MC and Koot, HM (2003) DSM-IV disorders in children with borderline to moderate intellectual disability. I. Prevalence and impact. Journal of the American Academy of Child & Adolescent Psychiatry 42, 915–922.Google Scholar
Dori, N, Green, T, Weizman, A and Gothelf, D (2017) The effectiveness and safety of antipsychotic and antidepressant medications in individuals with 22q11.2 deletion syndrome. Journal of Child and Adolescent Psychopharmacology 27, 83–90.Google Scholar
Dunn, V and Goodyer, IM (2006) Longitudinal investigation into childhood- and adolescence-onset depression: psychiatric outcome in early adulthood. The British Journal of Psychiatry: the Journal of Mental Science 188, 216–222.Google Scholar
Faraone, SV, Sergeant, J, Gillberg, C and Biederman, J (2003) The worldwide prevalence of ADHD: is it an American condition? World Psychiatry 2, 104–113.Google Scholar
Faraone, SV, Biederman, J and Mick, E (2006) The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychological Medicine 36, 159–165.Google Scholar
Gothelf, D, Feinstein, C, Thompson, T, Gu, E, Penniman, L, Van Stone, E, Kwon, H, Eliez, S and 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
Gothelf, D, Schneider, M, Green, T, Debbane, M, Frisch, A, Glaser, B, Zilkha, H, Schaer, M, Weizman, A and Eliez, S (2013) Risk factors and the evolution of psychosis in 22q11.2 deletion syndrome: a longitudinal 2-site study. Journal of the American Academy of Child and Adolescent Psychiatry 52, 1192–1203, e3.Google Scholar
Grati, FR, Molina Gomes, D, Ferreira, JC, Pinto, B, Dupont, C, Alesi, V, Gouas, L, Horelli-Kuitunen, N, Choy, KW, García-Herrero, S and Vega, AG (2015) Prevalence of recurrent pathogenic microdeletions and microduplications in over 9500 pregnancies. Prenatal Diagnosis 35, 801–809.Google Scholar
Green, T, Gothelf, D, Glaser, B, Debbane, M, Frisch, A, Kotler, M, Weizman, A and 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
Green, T, Weinberger, R, Diamond, A, Berant, M, Hirschfeld, L, Frisch, A, Zarchi, O, Weizman, A and Gothelf, D (2011) The effect of methylphenidate on prefrontal cognitive functioning, inattention, and hyperactivity in velocardiofacial syndrome. Journal of Child and Adolescent Psychopharmacology 21, 589–595.Google Scholar
Grover, RL, Ginsburg, GS and Ialongo, N (2005) Childhood predictors of anxiety symptoms: a longitudinal study. Child Psychiatry and Human Development 36, 133–153.Google Scholar
Hollingshead, AB (1975). Four factor index of social status. Unpublished Manuscript. Yale University: New Haven, CT.Google Scholar
Kates, W, Russo, N, Wood, W, Antshel, K, Faraone, S and Fremont, W (2015) Neurocognitive and familial moderators of psychiatric risk in velocardiofacial (22q11.2 deletion) syndrome: a longitudinal study. Psychological Medicine 45, 1629–1639.Google Scholar
Kessler, RC, McGonagle, KA, Zhao, S, Nelson, CB, Hughes, M, Eshleman, S, Wittchen, H and Kendler, KS (1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the national comorbidity survey. Archives of General Psychiatry 51, 8–19.Google Scholar
Kessler, RC, Avenevoli, S and Merikangas, KR (2001) Mood disorders in children and adolescents: an epidemiologic perspective. Biological Psychiatry 49, 1002–1014.Google Scholar
Knappe, S, Beesdo, K, Fehm, L, Höfler, M, Lieb, R and Wittchen, H (2009) Do parental psychopathology and unfavorable family environment predict the persistence of social phobia? Journal of Anxiety Disorders 23, 986–994.Google Scholar
Legerstee, JS, Verhulst, FC, Robbers, SC, Ormel, J, Oldehinkel, AJ and van Oort, FV (2013) Gender-specific developmental trajectories of anxiety during adolescence: determinants and outcomes. The TRAILS study. Journal of the Canadian Academy of Child and Adolescent Psychiatry 22, 26–34.Google Scholar
Lord, C, Rutter, M and Le Couteur, A (1994) Autism diagnostic interview-revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders 24, 695–685.Google Scholar
Mariano, MA, Tang, K, Kurtz, M and Kates, WR (2015) Cognitive remediation for adolescents with 22q11 deletion syndrome (22q11DS): a preliminary study examining effectiveness, feasibility, and fidelity of a hybrid strategy, remote and computer-based intervention. Schizophrenia Research 166, 283–289.Google Scholar
Mariano, MA, Tang, K, Kurtz, M and Kates, WR (2018) Examining the durability of a hybrid, remote and computer-based cognitive remediation intervention for adolescents with 22q11.2 deletion syndrome. Early Intervention in Psychiatry 12, 686–693.Google Scholar
Maughan, B (2013) Counting the cost: estimating the burden of child mental health. Journal of Child Psychology and Psychiatry 54, 1261–1262.Google Scholar
Merikangas, KR, He, JP, Burstein, M, Swanson, SA, Avenevoli, S, Cui, L, Benjet, C, Georgiades, K and Swendsen, J (2010) Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication – Adolescent Supplement (NCS-A). Journal of the American Academy of Child and Adolescent Psychiatry 49, 980–989.Google Scholar
Merikangas, KR, He, J, Rapoport, J, Vitiello, B and Olfson, M (2013) Medication use in US youth with mental disorders. JAMA Pediatrics 167, 141–148.Google Scholar
Murphy, KC, Jones, LA and Owen, MJ (1999) High rates of schizophrenia in adults with velo-cardio-facial syndrome. Archives of General Psychiatry 56, 940–945.Google Scholar
Platt, JM, Keyes, KM, McLaughlin, KA and Kaufman, AS (2018) Intellectual disability and mental disorders in a US population representative sample of adolescents. Psychological Medicine 12, 1–10. doi: https://doi.org/10.1017/S0033291718001605.Google Scholar
Reynolds, CR and Kamphaus, RW (1992) Behavior Assessment Scales for Children (BASC). Circle Pines, MN: American Guidance Service.Google Scholar
Rubin, D (2013) Conflicting data on psychotropic use by children: two pieces to the same puzzle. JAMA Pediatrics 167, 189–190.Google Scholar
Schneider, M, Debbané, M, Bassett, AS, Chow, EW, Fung, WLA, Van Den Bree, Van Den Bree MBM, , Owen, M, Murphy, KC, Niarchou, M and Kates, WR (2014) 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. American Journal of Psychiatry 171, 627–639.Google Scholar
Seguin, JR and Leckman, JF (2013) Developmental approaches to child psychopathology: longitudinal studies and implications for clinical practice. Journal of the Canadian Academy of Child and Adolescent Psychiatry 22, 3–5.Google Scholar
Shaffer, D, Gould, MS, Brasic, J, Ambrosini, P, Fisher, P, Bird, H and Aluwahlia, S (1983) A children's global assessment scale (CGAS). Archives of General Psychiatry 40, 1228–1231.Google Scholar
Skodol, AE, Geier, T, Grant, BF and Hasin, DS (2014) Personality disorders and the persistence of anxiety disorders in a nationally representative sample. Depression and Anxiety 31, 721–728.Google Scholar
Stoddard, J, Niendam, T, Hendren, R, Carter, C and Simon, TJ (2010) Attenuated positive symptoms of psychosis in adolescents with chromosome 22q11.2 deletion syndrome. Schizophrenia Research 118, 118–121.Google Scholar
Tang, S, Yi, J, Calkins, M, Whinna, D, Kohler, C, Souders, M, McDonald-McGinn, D, Zackai, E, Emanuel, B and Gur, R (2014) Psychiatric disorders in 22q11.2 deletion syndrome are prevalent but undertreated. Psychological Medicine 44, 1267–1277.Google Scholar
Tang, SX, Moore, TM, Calkins, ME, Yi, JJ, Savitt, A, Kohler, CG, Souders, MC, Zackai, EH, McDonald-McGinn, DM, Emanuel, BS, Gur, RC and Gur, RE (2017) The psychosis spectrum in 22q11.2 deletion syndrome is comparable to that of nondeleted youths. Biological Psychiatry 82, 17–25.Google Scholar
Taylor, LE, Kates, WR, Fremont, W and Antshel, KM (2018) Young adult outcomes for children with 22q11 deletion syndrome and comorbid ADHD. Journal of Pediatric Psychology 43, 636–644.Google Scholar
Vorstman, JA, Breetvelt, EJ, Duijff, SN, Eliez, S, Schneider, M, Jalbrzikowski, M, Armando, M, Vicari, S, Shashi, V, Hooper, SR, Chow, EW, Fung, WL, Butcher, NJ, Young, DA, McDonald-McGinn, DM, Vogels, A, van Amelsvoort, T, Gothelf, D, Weinberger, R, Weizman, A, Klaassen, PW, Koops, S, Kates, WR, Antshel, KM, Simon, TJ, Ousley, OY, Swillen, A, Gur, RE, Bearden, CE, Kahn, RS, Bassett, AS; International Consortium on, Brain and Behavior, in 22q11.2 Deletion, Syndrome (2015) Cognitive decline preceding the onset of psychosis in patients with 22q11. 2 deletion syndrome. JAMA psychiatry, 72, 377–385.Google Scholar
Wechsler, D (1997) Wechsler Adult Intelligence Scale, 3rd Edn. San Antonio, TX: Psychological Corporation.Google Scholar
Weinberger, R, Weisman, O, Guri, Y, Harel, T, Weizman, A and Gothelf, D (2018) The interaction between neurocognitive functioning, subthreshold psychotic symptoms and pharmacotherapy in 22q11.2 deletion syndrome: a longitudinal comparative study. European psychiatry: the journal of the Association of European Psychiatrists 48, 20–26.Google Scholar
Yi, JJ, Calkins, ME, Tang, SX, Kohler, CG, McDonald-McGinn, DM, Zackai, EH, Savitt, AP, Bilker, WB, Whinna, DA, Souders, MC, Emanuel, BS, Gur, RC and Gur, RE (2015) Impact of psychiatric comorbidity and cognitive deficit on function in 22q11.2 deletion syndrome. The Journal of Clinical Psychiatry 76, e1262–e1270.Google Scholar
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