Review
Systematic Review and Meta-analysis: Mental Health in Children With Neurogenetic Disorders Associated With Intellectual Disability

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Objective

The behavioral phenotype of neurogenetic disorders associated with intellectual disability often includes psychiatric comorbidity. The objectives of this systematic review and meta-analysis were to systematically review the prevalence of psychiatric disorders and symptoms in children and adolescents with these disorders and compare phenotypic signatures between syndromes.

Method

MEDLINE and PsycINFO databases were searched for articles from study inception to December 2018. Eligible articles were peer reviewed, were published in English, and reported prevalence data for psychiatric disorders and symptoms in children and adolescents aged 4 to 21 years using a formal psychiatric assessment or a standardized assessment of mental health symptoms. Pooled prevalence was determined using a random-effects meta-analysis in studies with sufficient data. Prevalence estimates were compared with general population data using a test of binomial proportions.

Results

Of 2,301 studies identified for review, 39 articles were included in the final pool, which provided data on 4,039 children and adolescents. Ten syndromes were represented, and five were predominant: Down syndrome, 22q11.2 deletion syndrome, fragile X syndrome, Williams syndrome, and Prader-Willi syndrome. The Child Behavior Checklist was the most commonly used assessment tool for psychiatric symptoms. The pooled prevalence with total scores above the clinical threshold was lowest for Down syndrome (32% [95% confidence interval, 19%-44%]) and highest for Prader-Willi syndrome (74% [95% CI, 65%-82%]) with each syndrome associated with significantly higher prevalence than in the general population. Parallel trends were observed for the internalizing and externalizing domains and social subscale scores.

Conclusion

Differential vulnerability for psychiatric phenotype expression across the disorders was observed. Syndromes with higher levels of social ability or competence appear to offer relative protection against developing psychopathology. This preliminary finding merits further exploration.

Section snippets

Method

This review was structured and executed according to the PRISMA checklist (Figure 1).22

Results

The initial search yielded 2,301 records, of which 39 were suitable for inclusion. The resulting pool of articles contained data for 4,039 children and adolescents.

Discussion

Prevalence studies of psychiatric diagnoses in children and adolescents with a neurogenetic disorder associated with ID are relatively sparse, but estimates appeared to be higher than in the general population. We found data to indicate that 8% of children with Down syndrome and 20% of children with Prader-Willi syndrome were diagnosed with any disruptive disorder, higher than the worldwide pooled prevalence of 5.7% for children and adolescents in the general population.75 Our pooled prevalence

References (98)

  • C. Sobin et al.

    Sex differences in the behavior of children with the 22q11 deletion syndrome

    Psychiatry Res

    (2009)
  • A.S. Young et al.

    Discordance in diagnoses and treatment of psychiatric disorders in children and adolescents with 22q11.2 deletion syndrome

    Asian J Psychiatr

    (2011)
  • J. Niemczyk et al.

    Incontinence and psychological symptoms in individuals with Mowat-Wilson syndrome

    Res Dev Disabil

    (2017)
  • R.T. Schultz et al.

    Genetics of childhood disorders: XXVI. Williams syndrome and brain-behavior relationships

    J Am Acad Child Adolesc Psychiatry

    (2001)
  • D.P. Carney et al.

    Executive function in Williams and Down syndromes

    Res Dev Disabil

    (2013)
  • W.E. Copeland et al.

    Longitudinal patterns of anxiety from childhood to adulthood: the Great Smoky Mountains Study

    J Am Acad Child Adolesc Psychiatry

    (2014)
  • J. Biederman et al.

    CBCL clinical scales discriminate prepubertal children with structured interview-derived diagnosis of mania from those with ADHD

    J Am Acad Child Adolesc Psychiatry

    (1995)
  • B.H. King et al.

    Mental retardation: a review of the past 10 years. Part I

    J Am Acad Child Adolesc Psychiatry

    (1997)
  • M.W. State et al.

    Mental retardation: a review of the past 10 years. Part II

    J Am Acad Child Adolesc Psychiatry

    (1997)
  • P.J. Easterbrook et al.

    Publication bias in clinical research

    Lancet

    (1991)
  • K.M. Gray et al.

    The longitudinal relationship between behavior and emotional disturbance in young people with intellectual disability and maternal mental health

    Res Dev Disabil

    (2011)
  • J.E. Roberts et al.

    Trajectory and predictors of depression and anxiety disorders in mothers with the FMR1 premutation

    Biol Psychiatry

    (2016)
  • M.C. Dekker et al.

    DSM-IV disorders in children with borderline to moderate intellectual disability. II. Child and family predictors

    J Am Acad Child Adolesc Psychiatry

    (2003)
  • D. Grafodatskaya et al.

    Autism spectrum disorders and epigenetics

    J Am Acad Child Adolesc Psychiatry

    (2010)
  • P.J. Lombroso

    Genetics of childhood disorders: XLVIII. Learning and memory, part 1: fragile X syndrome update

    J Am Acad Child Adolesc Psychiatry

    (2003)
  • J. Bourke et al.

    Population-based prevalence of intellectual disability and autism spectrum disorders in Western Australia: a comparison with previous estimates

    Medicine (Baltimore)

    (2016)
  • H. Leonard et al.

    Relation between intrauterine growth and subsequent intellectual disability in a ten-year population cohort of children in Western Australia

    Am J Epidemiol

    (2007)
  • L.E. Vissers et al.

    Genetic studies in intellectual disability and related disorders

    Nat Rev Genet

    (2016)
  • S.E. Antonarakis

    Down syndrome and the complexity of genome dosage imbalance

    Nat Rev Genet

    (2017)
  • D.I. Ward et al.

    Intellectual disability and epilepsy due to the K/L-mediated Xq28 duplication: further evidence of a distinct, dosage-dependent phenotype

    Am J Med Genet A

    (2018)
  • S.E. Parker et al.

    Updated national birth prevalence estimates for selected birth defects in the United States, 2004-2006

    Birth Defects Res A Clin Mol Teratol

    (2010)
  • K. Devriendt et al.

    The annual incidence of DiGeorge/velocardiofacial syndrome

    J Med Genet

    (1998)
  • J.V. Butler et al.

    Prevalence of, and risk factors for, physical ill-health in people with Prader-Willi syndrome: a population-based study

    Dev Med Child Neurol

    (2002)
  • S. Fehr et al.

    Trends in the diagnosis of Rett syndrome in Australia

    Pediatr Res

    (2011)
  • R.M. Hodapp

    Direct and indirect behavioral effects of different genetic disorders of mental retardation

    Am J Ment Retard

    (1997)
  • K.B. Naess et al.

    The profile of social functioning in children with Down syndrome

    Disabil Rehabil

    (2017)
  • M. Karayiorgou et al.

    22q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia

    Nat Rev Neurosci

    (2010)
  • S.L. Einfeld et al.

    Comorbidity of intellectual disability and mental disorder in children and adolescents: a systematic review

    J Intellect Dev Disabil

    (2011)
  • K.R. Foley et al.

    Patterns of depressive symptoms and social relating behaviors differ over time from other behavioral domains for young people with Down syndrome

    Medicine (Baltimore)

    (2015)
  • O. Leyfer et al.

    Anxiety disorders in children with Williams syndrome, their mothers, and their siblings: implications for the etiology of anxiety disorders

    J Neurodev Disord

    (2009)
  • Mental Health Atlas 2017

    (2017)
  • S. Saxena et al.

    World Health Organization’s Comprehensive Mental Health Action Plan 2013–2020

    Psychiatry Clin Neurosci

    (2014)
  • S.A. Cooper et al.

    Mental ill-health in adults with intellectual disabilities: prevalence and associated factors

    Br J Psychiatry

    (2007)
  • J. Ji

    Distinguishing subclinical (subthreshold) depression from the residual symptoms of major depression

    Shanghai Arch Psychiatry

    (2012)
  • International Statistical Classification of Diseases and Related Health Problems

    (2004)
  • Diagnostic and Statistical Manual of Mental Disorders

    (2013)
  • T.M. Achenbach

    Manual for the Child Behavior Checklist/4-18 and 1991 Profile

    (1991)
  • S.L. Einfeld et al.

    Manual for the Developmental Behaviour Checklist: Primary Carer Version (DBC-P) and Teacher Version (DBC-T)

    (2002)
  • M. Schneider et al.

    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

    Am J Psychiatry

    (2014)
  • Cited by (0)

    The authors have acknowledged seed funding from the Telethon Kids Institute, Perth, Australia, and the Western Australian Department of Health, Perth, Australia, who supported this study with a Merit Award.

    Mr. Jacoby served as the statistical expert for this research.

    Disclosure: Drs. Leonard and Downs have consulted for AveXis, GW Pharmaceuticals, Anavex, and Marinus Pharmaceuticals. Drs. Glasson, Chen, Skoss, Blackmore, Mr. Buckley, Ms. Epstein, Mr. Jacoby, and Ms. Bourke have reported no biomedical financial interests or potential conflicts of interest.

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