CHRNA7 Deletions are Enriched in Risperidone-Treated Children and Adolescents
Open accessAbstract
OBJECTIVE: Aggression is among the most common indications for referral to child and adolescent mental health services and is often challenging to treat. Understanding the biological underpinnings of aggression could help optimize treatment efficacy. Neuronal nicotinic acetylcholine receptors (nAChRs), specifically the α7 nAChR, encoded by the gene CHRNA7, have been implicated in aggressive behaviors in animal models as well as humans. Copy number variants (CNVs) of CHRNA7 are found in individuals with neuropsychiatric disorders, often with comorbid aggression. In this study, we aimed to determine the prevalence of CHRNA7 CNVs among individuals treated with risperidone, predominantly for irritability and aggression. METHODS: Risperidone-treated children and adolescents were assessed for CHRNA7 copy number state using droplet digital PCR and genomic quantitative PCR. Demographic, anthropometric, and clinical data, including the Child Behavior Checklist (CBCL), were collected and compared across individuals with and without the CHRNA7 deletion. RESULTS: Of 218 individuals (90% males, mean age: 12.3 ± 2.3 years), 7 (3.2%) were found to carry a CHRNA7 deletion and one proband carried a CHRNA7 duplication (0.46%). T-scores for rule breaking, aggression, and externalizing behavior factors of the CBCL were higher in the deletion group, despite taking 58% higher dose of risperidone. CONCLUSIONS: CHRNA7 loss may contribute to a phenotype of severe aggression. Given the high prevalence of the deletion among risperidone-treated youth, future studies should examine the therapeutic potential of α7 nAChR-targeting drugs to target aggression associated with CHRNA7 deletions.
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CHRNA7 deletion probands had significantly higher T scores than copy-neutral probands, even after accounting for age, sex, and weight-adjusted dose of risperidone and psychostimulants (b = 13.7, SE = 6.4, Cohen's d = 1.26, p = 0.0340 for aggression).
“CHRNA7 dedeletion probands had significantly higher T scores than copy-neutral probands, even after accounting for age, sex, and weight-adjusted dose of risperidone and psychostimulants (b = 13.7, SE = 6.4, Cohen’s d = 1.26, p = 0.0340 for aggression)”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Gillentine [166]
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- Authors
- Gillentine, M. A., White, J. J., Grochowski, C. M., Lupski, J. R., Schaaf, C. P., & Calarge, C. A.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Schaaf, Christian P.
- Calarge, Chadi A.
- ORCID
- Venue
- Journal of Child and Adolescent Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2017-12
- Volume
- 27
- Issue
- 10
- Pages
- 908-915
- ISSN
- 1044-5463 (ISSN-L)
- 1557-8992
- PMC
- PMC5725633
- OpenAlex
- W2745482835
- Cited by
- 11
- References
- 35
- Citations by year
- 2026: 1 · 2024: 2 · 2022: 2 · 2021: 1 · 2019: 2 · 2018: 2 · 2017: 1
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Child and Adolescent Psychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM008307)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- CHRNA7, copy number variation, alpha7 nicotinic acetylcholine receptor, aggression, irritability, risperidone, children and adolescents, externalizing problems, rule violations, antipsychotic drugs
- MeSH terms
- Adolescent, Child, Female, Humans, Male, Prospective Studies, Antipsychotic Agents, Cohort Studies, Treatment Outcome, Gene Deletion, Risperidone, alpha7 Nicotinic Acetylcholine Receptor, Neurodevelopmental Disorders
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