Psychiatric disorders in children with 16p11.2 deletion and duplication
Open accessAbstract
Deletion and duplication of 16p11.2 (BP4–BP5) have been associated with an increased risk of intellectual disability and psychiatric disorder. This is the first study to compare the frequency of a broad spectrum of psychiatric disorders in children with 16p11.2 deletion and duplication. We aimed to evaluate (1) the nature and prevalence of psychopathology associated with copy number variation (CNV) in children with 16p11.2 by comparing deletion and duplication carriers with family controls; (2) whether deletion and duplication carriers differ in frequency of psychopathology. 217 deletion carriers, 77 deletion family controls, 114 duplication carriers, and 32 duplication family controls participated in the study. Measures included standardized research diagnostic instruments. Deletion carriers had a higher frequency of any psychiatric disorder (OR = 8.9, p < 0.001), attention deficit hyperactivity disorder (ADHD) (OR = 4.0, p = 0.01), and autism spectrum disorder (ASD) (OR = 39.9, p = 0.01) than controls. Duplication carriers had a higher frequency of any psychiatric diagnosis (OR = 5.3, p = 0.01) and ADHD (OR = 7.0, p = 0.02) than controls. The prevalence of ASD in child carriers of deletions and duplications was similar (22% versus 26%). Comparison of the two CNV groups indicated a higher frequency of ADHD in children with the duplication than deletion (OR = 2.7, p = 0.04) as well as a higher frequency of overall psychiatric disorders (OR = 2.8, p = 0.02) and psychotic symptoms (OR = 4.7, p = 0.02). However, no differences between deletion and duplications carriers in the prevalence of ASD were found. Both deletion and duplication are associated with an increased risk of psychiatric disorder, supporting the importance of early recognition, diagnosis, and intervention in these groups.
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The more severe outcomes associated with 16p11.2 deletions prevent these patients from having children, leading to lower rates of inherited deletions.
“The more severe outcomes associated with 16p11.2 deletions preclude these patients from having children, resulting in lower rates of inherited deletions [34].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [34]
In studies with at least 50 subjects, 60-76% of 16p11.2 deletions were reported as de novo, while only 16-29% of 16p11.2 duplications occurred de novo.
“In studies with at least 50 subjects, between 60–76% of 16p11.2 deletions were reported as de novo events [10, 12, 34, 36], while only 16–29% of 16p11.2 duplications occurred de novo [10, 19, 34, 36].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [34]
Psychotic symptoms have been reported in 6.1% of 16p11.2 duplication carriers and 2.3% of deletion carriers.
“Psychotic symptoms have also been reported in duplication (7/114 [6.1%]) and deletion (5/217 [2.3%]) carriers [34].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [34]
16p11.2 deletions and duplications are linked to depression and anxiety.
“16p11.2 deletions and duplications are linked to several other psychiatric conditions, including depression [14, 47] and anxiety [12, 14, 18, 19, 23, 34].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [34]
ADHD is observed in 16p11.2 CNV carriers at rates as high as 29% (63/217) in deletion carriers and 42% (48/114) in duplication carriers.
“Attention-deficit/hyperactivity disorder (ADHD) is also observed in 16p11.2 CNV carriers [12, 15–17, 19, 23, 48], at rates as high as 29% (63/217) and 42% (48/114) in deletion and duplication carriers, respectively [34].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [34]
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- Authors
- Niarchou, M., Chawner, S. J. R. A., Doherty, J. L., Maillard, A. M., Jacquemont, S., Chung, W. K., Green-Snyder, L., Bernier, R. A., Goin-Kochel, R. P., Hanson, E., Linden, D. E. J., Linden, S. C., Raymond, F. L., Skuse, D., Hall, J., Owen, M. J., & Bree, M. B. M. V. D.
- Affiliations
- The University of Queensland (AU)
- Cardiff University (GB)
- Centre Hospitalier Universitaire Vaudois (CH)
- Columbia University (US)
- University of Washington (US)
- Boston Children's Hospital (US)
- University of Cambridge (GB)
- University College London (GB)
- Corresponding author
- Niarchou, Maria
- Bree, Marianne B. M. van den
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2019-01-16
- Volume
- 9
- Issue
- 1
- Pages
- 8-8
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC6341088
- OpenAlex
- W2902341898
- Cited by
- 156
- References
- 10
- Citations by year
- 2026: 14 · 2025: 25 · 2024: 20 · 2023: 16 · 2022: 19 · 2021: 27 · 2020: 24 · 2019: 10 · 2018: 1
- FWCI
- 12.05
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-03-05)
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- IRIS (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Simons Foundation
- Wellcome Trust (110222, /Z/15/Z, 110222/Z/15/Z, G0801418)
- Medical Research Council (G0801418, MR/P005748/1, MR/N022572/1, MR/L010305/1, MR/L011166/1, G0800509)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD083091)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- 16p11.2 deletion, 16p11.2 duplication, copy number variation, mental illness, attention deficit hyperactivity disorder, autism spectrum disorder, psychotic symptoms, intellectual disability, children, genetic risk
- MeSH terms
- Autism Spectrum Disorder, Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Chromosomes, Human, Pair 16, Female, Heterozygote, Humans, Male, Case-Control Studies, Sequence Deletion, DNA Copy Number Variations, Chromosome Duplication
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